The impact of immunosuppression despite virological suppression  on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated.Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4<350 cells/µl and viral load (VL)>500 copies/mL were followed-up from the first day of VL< = 50 copies/ml until a new fatal/non-fatal non-AIDS/AIDS event. Considered non-AIDS events included non-AIDS malignancies, pancreatitis, severe liver disease with hepatic encephalopathy (>grade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models.2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96  in unadjusted analysis and 1.43  after controlling for current CD4 count. ID was not associated with the risk of AIDS events .Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART. Combination antiretroviral therapy (cART) mainly exerts its effect on the reduction of HIV related morbidity and mortality by suppressing HIV viral load which leads to an increase of CD4 cells The EuroSIDA study is a prospective, observational cohort study including HIV-1 infected patients from 31 European countries as well as Israel and Argentina To date, nine cohorts have been enrolled starting in May 1994. At enrollment, demographic characteristics and clinical information are obtained. Every 6 months CD4 count and viral load data as well as data on antiretroviral drugs used are collected in a standardized report form and forwarded to the coordinating center. The pre-specified non-AIDS events included are those used in previous EuroSIDA publications on this topic www.cphiv.dk.Each of the centers participating in EuroSIDA sought ethical clearance according to local regulations and laws and patients gave their informed consent to take part in the study. All data were anonymized prior to statistical analysis. The senior investigator at each clinical site is responsible for obtaining and maintaining this/these approval(s) at all times during the conduct of the study. Full study details are available at Patients in the cohort with a CD4 count of less than 350 cells/µl who after 1 January 2001 started at least one new antiretroviral drug with most recent viral load >500 copies/mL (either because starting their first cART or because switching drugs after failing on their previous regimen) and subsequently achieved viral suppression < = 50 copies/mL were included. Follow-up accrued from the first day of viral suppression below 50 copies/mL following the initiation of the new regimen (baseline) until the first of either a fatal or non-fatal non-AIDS or AIDS event, viral rebound >50 copies/mL  or patients’ latest available follow-up visit in which they were known to be still event-free. Each AIDS and non-AIDS condition which developed during follow-up was counted as one event and recurrences of the same condition were not counted.Data were left-censored at entry in the cohort and patients had to have at least one month of prospective follow-up after baseline to be included. CD4 counts were carried forward until a new CD4 test was performed.Immuno-virological response was defined using both the CD4 count measured prior to initiation of the suppressive regimen and the current CD4 count. In particular if patients’ current CD4 count was still equal or below the pre-ART initiation level then the person was defined as immuno-virological discordant (ID) at the time of the current CD4 count measure. In contrast, any current rise in CD4 count above pre-ART level would reverse his/her classification to immunological responder (non-ID). Rates of fatal and non-fatal non-AIDS and AIDS events were calculated over 6 monthly periods  of virological suppression after baseline and stratified according to ID status. Univariable and multivariable Poisson regression models were performed to estimate the risk associated with a current ID status (fitted as a time-dependent covariate). When exploring the magnitude of the risk associated with being ID over time, a categorical covariate grouping periods of follow-up with thresholds 0–6, 7–12, 13–18, 19–24, >24 months and using the 0–6 months period as the comparator group was included in the model. Other potential risk factors or confounders which were considered for inclusion in the model were: age, hepatitis C serostatus, mode of HIV transmission, race, cohort of origin, the number of previous ART regimens used, current CD4 count  and specific antiretroviral drugs included in the newly initiated regimen.Potential confounders were selected on the basis of prior knowledge and when hypothesized to be common causes of both the exposure of interest and the risk of developing the outcome. A software based on directed acyclic graphs 2), anaemia , diabetes (defined as having previously started any antidiabetic treatment or diagnosis of insulin dependent diabetes), and hypertension (defined as a systolic/diastolic blood pressure> = 140/> = 90 mmHg mmHg or previous initiation of any antihypertensive treatment).To be consistent with previous analysis of the data of the cohort, current CD4 count was fitted on a log2 scale as this was shown to improve the goodness of fit of the model. Models also included time from initiation of new regimen to viral suppression, current or previous smoking, history of impaired renal function at baseline  using a competing risk approach . In brief, the competing event  was removed to avoid overestimation of the cumulative probability of AIDS events The likelihood ratio test was used to test temporal trends and, more in general, to compare the difference in goodness of fit of nested models (for example models with or without specific interaction terms). STATA v12.1 was used for all analyses. All p-values were two sided and a value of <0.05 was considered significant unless it was a subgroup analysis for which we required the p-value to be smaller than 0.05/k where k was the total number of identified groups (Bonferroni correction).A total of 2,913 patients satisfied the inclusion criteria for this analysis . Median For the primary endpoint, fatal and non-fatal non-AIDS, 11,491 person years of follow-up were available and 241 events including 157 non-AIDS disease events and 84 non-AIDS deaths occurred. Malignancies classified as not AIDS related were the most common disease events  followed by cerebrovascular diseases . Kaplan Meier estimate of median survival time in patients who died was 2.1 (95% CI 1.6–2.8) years. Malignancies  were also the most common causes of death. 42 (17%) fatal or non-fatal non-AIDS events occurred in ID patients  vs. 199 (83%) in patients without ID  p<0.001 .In the adjusted Poisson regression analysis including demographic and clinical parameters ; model 1Compared to the first 6 months of viral suppression (reference group), the adjusted relative rate of experiencing fatal or non-fatal non-AIDS for patients classified as ID was 1.06 (95% CI 0.32–3.50) in month 7–12, 0.81 (95% CI 0.23–2.81) in month 13–18, 1.67 (95% CI 0.51–5.41) in month 19–24 and 0.91 (95% CI 0.23–3.60) thereafter, test for trend p = 1.00). Similarly, there was no tendency for a decline in risk in periods in which patients were classified as non-ID .Factors besides ID and current CD4 count significantly associated with the risk of developing the composite endpoint in the main analysis included older age, a diagnosis of anaemia prior to baseline, previous non-AIDS, and current use of antiretroviral treatment consisting of less than 3 drugs .The association between ID and the risk of non-AIDS events appeared to be higher in patients who were therapy-naïve  vs. those who were treatment experienced  at baseline, although there was no evidence of interaction .After restricting our analysis to patients who achieved viral suppression within one year after initiation of cART , the association between ID and the risk of developing non-AIDS events  was consistent with that found in the main analysis. In a sub-analysis of ART naïve patients who achieved complete virological suppression within one year (21 events only), ID was marginally significantly associated with non-AIDS even after controlling for current CD4 .Results were similar in a sensitivity analysis defining virological failure as one viral load >50 regardless of confirmation (data not shown).In the analysis using the alternative cut-off of 200 CD4 cells/µl , results were also similar: aRR 2.39, 95% CI 1.37–4.18, p = 0.002) in the model adjusted only for demographic and clinical factors and aRR 1.58, 95% CI 0.81–3.12, p = 0.183) after further controlling for current CD4 count.In the separate analysis with AIDS as an endpoint, 11,723 person years of follow-up were available. A total of 89 AIDS events including 10 AIDS-related deaths occurred. Oesophageal candidiasis was a frequently observed opportunistic infection  followed by pulmonary and extrapulmonary tuberculosis . Kaplan Meier estimate of median survival time in patients who died was 1.3 (95% CI 0.3–2.0) years. AIDS malignancies were the most common cause .ID was significantly associated with the risk of developing AIDS-related events when adjusted for demographic and clinical factors only . However, after adjusting for current CD4 count, ID was no longer independently associated . Factors significantly associated with the risk of developing AIDS included current CD4 , diagnosis of anaemia at baseline , and a previous AIDS condition .In our analysis, we found that people who failed to achieve a CD4 count above the level present at the time of starting a new regimen, despite having achieved and maintained viral suppression <50 copies/mL on ART, tended to have an increased risk of developing non-AIDS morbidity and mortality. Because of the wide confidence interval around our estimate, our results may be considered inconclusive. However, a two-fold increased risk in people with ID cannot be excluded. Our results should guide further investigations using larger study populations to test whether the lack of statistical significance was due to limited power of our analysis. Of note, the association was independent of demographic characteristics and baseline CD4 count but seemed to be mainly explained by a low current CD4 count. There was a small residual independent effect but only in people who started the new regimen when they were ART-naïve and who achieve virological suppression within one year. In additions, there was no evidence for a decreasing risk of non-AIDS events with longer time with a viral load < = 50 copies/mL in people with or without ID.Our data suggest that in order to reduce the risk of non-AIDS events in people starting therapy with a CD4<350 cells/µl, continuous monitoring for difference between current CD4 count and the level registered at the time of initiation of a new regimen may be considered starting as early as the first 6 months following viral suppression. The cut-off of 350 CD4 cells/µl as baseline was chosen as this represents the threshold below which cART is generally recommended. However, also when the alternative cut-off of 200 CD4 cells/µl was used, our results were similar although the analyses had reduced statistical power.In a previous analysis, ID was associated with a higher risk of AIDS and death Previous analyses of EuroSIDA data demonstrated that current CD4 count is a significant predictor of the risk of non-AIDS events although the association was less strong than that found for AIDS events In the present study we included time-updated current CD4 count and immuno-virological discordance status, because we hypothesized that the risk associated with the incapacity to reconstitute CD4 cells over time may not be fully captured by current CD4 count without taking into account the status of immunosuppression observed prior to starting the suppressive regimen. A similar approach was also used in a recent study by Lapadula et al who, however, used a different definition of non-AIDS events but a similar definition of ID patients and found a strong association between lack of CD4 count recovery on suppressive ART and risk of developing the composite endpoint of AIDS and non-AIDS events The finding for non-AIDS events is intriguing as it suggests that patients’ current status of immunodeficiency is not able to fully explain why some people remain at higher risk of clinical complications. However, this needs to be confirmed in further analyses as measurement variability in CD4 tests and differences in frequencies of measurement may be alternative explanations.Indeed, it is possible that ID is a marker of one of more unmeasured factors that put these people at increased risk of an adverse clinical outcome. For example, immuno-virological discordance may be the effect of incomplete bone marrow or thymus output as well as excessive destruction or disturbed immunoregulation. Our study has some limitations: first, the non-AIDS conditions considered here as endpoint-defining events represent a subset of non-AIDS events causing HIV morbidity. However, this selection has been previously used In conclusion, patients with immuno-virological discordance, in the context of suppressed viral load appeared to be at higher risk of fatal and non-fatal non-AIDS events although most of this increased risk seems to be explained by a low current CD4 count. An independent effect was found only in the subset of ART-naïve patients who experienced a rapid virological response. Another important finding was that this increased risk, if it exists, does not seem to decrease with longer duration of viral suppression, suggesting that such patients should remain under close follow-up for change in CD4 count from pre-therapy level, also after extended periods of being on cART. If this observation is confirmed in other studies it has profound implications as it suggests that cART alone may not be able to substantially remove the risk of non-AIDS in patients identified as ID. To date, strategies to directly influence immune reconstitution by adding interleukin-2 or by modifying cART regimens have failed to show benefit over viral suppression alone


Guidelines to treat acute otitis media (AOM) were published in 2004. Initial declines in prescribing were shown, but it's unknown if they were sustained. We examine trends in antibiotic dispensing patterns to treat AOM among a large population of children. We also document trends in antibiotic failure.Children aged 3 months to 12 years with an AOM diagnosis, enrolled in a commercial claims database between January 1, 2000-December 31, 2011 were included. Pharmacy claims within 7 days of diagnosis were searched for antibiotic prescriptions. Antibiotic failure was defined as a dispensing of a different antibiotic class within 2-18 days after the first prescription. We analyzed trends in antibiotic use and failure by class of antibiotic and year.We identified over 4 million children under 13 years with AOM. The proportion of antibiotic dispensing decreased from 66.0% in 2005 to 51.9% in 2007, after which the instances of dispensing rebounded to pre-guideline levels. However, levels began decreasing again in 2010 and the antibiotic use rate in 2011 was 57.6%. Cephalosporin prescriptions increased by 41.5% over eleven years. Antibiotic failure decreased slightly, and macrolides had the lowest proportion of failures, while all other classes had failure rates around 10%.In recent years, antibiotic dispensing to treat AOM remains high. In addition, the use of broad-spectrum antibiotics is increasing despite having a high rate of treatment failure. Overprescribing of antibiotics and use of non-penicillin therapy for AOM treatment could lead to the development of antibiotic-resistant infections. In children, acute otitis media (AOM) is one of the most common infections for which antibiotics are prescribed.Because of the detrimental effects of over-prescribing antibiotics, there has been a considerable effort to understand how the use of these drugs has changed over time. Several studies in the late 1990s showed that overall antibiotic prescribing was decreasing even prior to the AAP/AAFP guidelines;To address these gaps in knowledge, we sought to examine treatment patterns for AOM among a very large population of children with commercial insurance using contemporary data. We report proportions of dispensed antibiotic prescriptions to treat AOM five years before and seven years after the initial 2004 AAP/AAFP guidelines. We also examine trends in antibiotic failure over time and compare the risk of failure by type of initial prescription.We analyzed data from the MarketScan Commercial Claims and Encounters database  between January 1, 2000-December 31, 2011. The data capture patient-level data on inpatient, outpatient, and prescription drug claims from approximately 150 large employers and health plans that insure employees, early retirees and dependents. This database includes 23 million children over ten years. Drug information represents prescriptions that were collected at a pharmacy.International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. We identified children with a diagnosis code for AOM as either the primary or secondary diagnosis by the following ICD-9-CM codes: 382.x, 384.2. These codes were chosen as the AAP/AAFP guidelines were specific to these conditions. We also compared our main cohort to children with a diagnosis of otitis media with effusion (OME) (codes 381.0-381.4) – while the guidelines were not focused on these conditions; we thought it useful to also characterize prescribing trends for children with an otitis media diagnosis where clinical guidelines suggest using antibiotics less often. Children had to be enrolled for at least 90 days without an otitis media diagnoses to be considered a new illness episode. We analyzed only the first new illness episode per child, to make sure we did not include recurrent disease. We further categorized children into age categories: <2 years, 2–3 years, and 4+ years as prescribing patterns could vary by age.Children aged 3 months to 12 years were included in the study sample. Outpatient diagnoses are coded using ICD-9-CM codes: 003–006, 033–034, 036, 038, 320, 322, 466.0, 481–486, 599.0).For the initial otitis media diagnosis, we searched prescription drug claims for all types of oral antibiotics. A drug claim was considered linked to an outpatient diagnosis if it occurred within 7 days of the outpatient visit. We divided antibiotics into six categories: amoxicillin, amoxicillin/clavulanate, unspecified penicillins, macrolides, cephalosporins, and other antibiotics. If more than one antibiotic was filled during the week following the diagnosis, we counted each antibiotic in its respective class, but the encounter only counted once as a visit for which antibiotics were prescribed. Antibiotic failure was defined as children who filled a prescription for an oral antibiotic, or were given injectable or intravenous antibiotics .This study was approved by the institutional review board of University of North Carolina at Chapel Hill. As this study used de-identified data as a secondary data analysis and was classified as research involving no greater than minimal risk, the requirement of obtaining informed consent was waived.There were 4,629,460 children aged 3 months – 12 years identified with an AOM diagnosis, after dropping 101 children who had a missing age. Overall, the mean age of the cohort was 3.8 years, while the median was 3.0 years. Children who were given antibiotics were of similar age and gender as those who were untreated . There wOver the 12 year period, 60.1% of children with AOM diagnoses were dispensed antibiotics. The proportion of dispensing decreased from 66.0% in 2005 to 51.9% in 2007, after which the instances of antibiotic dispensing rebounded to pre-AAP/AAFP guideline levels. However, levels began decreasing again in 2010 and antibiotic use in 2011 was 57.6%. Of all antibiotics dispensed, 54% were for amoxicillin. Use of amoxicillin decreased slightly – from 57% to 53% between 2005–2008, but increased to pre-guideline levels by 2011 . This trOverall, non-amoxicillin containing antibiotics represented 30.6% of all first antibiotic dispensings. While macrolide use remained constant at ∼13% of dispensed antibiotic prescriptions and amoxicillin/clavulanate declined slightly (p = 0.002), cephalosporin use increased over time. Cephalosporin prescriptions increased from a low of 12.3% in 2001, peaked in 2007, and leveled out at 17.4% in 2011 (p = 0.0004). This was a 41.5% increase over eleven years. . CefdiniAmong children with AOM and with one initial prescription, 10.1% required an additional antibiotic within 2–18 days over the 12 year period . AntibioIn this large, commercially-insured population of children following the initial 2004 AAP/AAFP guidelines, we observed an initial decrease in encounters with dispensed antibiotics to a low of 51.9%. These estimates are lower than a study limited to two years after the implementation of the guidelines, which estimated that 84% of children were given prescriptions.We observed that the decline in dispensing following the implementation of the initial guidelines was not sustained. Although most recent data suggests that dispensing is again on the decline, antibiotic use has been near pre-guideline levels in years after 2007. This could indicate that physicians may have returned to past prescribing patterns. This agrees with a survey of physicians that reported increasing discordancy with the guidelines in choice of prescribed antibiotics over time.Additionally, we showed an increasing use in cephalosporins used as initial treatment for AOM. Other studies have shown similar increases for non-first-line antibiotics, particularly with the antibiotic cefdinir.Streptococcus pneumoniae since the introduction of the pneumococcal conjugate vaccine (PCV). PCV-7 was introduced in 2001,Streptococcus pneumoniae was a leading cause of AOMS. pneumonia, as well as decreasing antibiotic resistant strains.An encouraging finding is that treatment failures have decreased, even with an increase in overall treatment since the initial guidelines were published. Our estimates are similar to the decreasing trend reported in a large, observational study of children in Boston treated with high-dose amoxicillin, where the relapse rate was 8.9% in 2004.We also show that macrolides had a lower failure rate, while cephalosporins, amoxicillin, and amoxicillin/clavulanate had similar, higher rates of failure. Interestingly, macrolides had a higher failure rate in the early failure window (3–7) days, but had a lower failure rate in the late failure window. Possible explanations for the lower overall rates of failure seen among macrolides could be that physicians are using these drugs to treat to viral infections, which would have resolved regardless of treatment, or that the shorter course (5 days) results in higher compliance and better outcomes. Recent studies have reported contradictory results when comparing failure rates between classes of antibiotics. One population based, observational study reported similar positive findings for macrolides as our study- azithromycin had a 12% lower odds of failure as compared to amoxicillin._ENREF_22There were several limitations to this study. First, we were unable to distinguish the cause of the changing trends in treatment patterns. It is possible that treatment patterns did actually change in response to the guidelines. However, it is also possible that the diagnosis of acute otitis media changed over time – if physicians were diagnosing milder cases, this could create an appearance of a decreased treatment effect. Therefore, it is possible that the decrease in overall dispensing we showed between 2005 and 2007 was due to a change in diagnosing, as opposed to a change in treatment patterns. Second, we did not have information on weight in the dataset. This prohibited the assessment of whether a certain antibiotic was classified as “high-dose,” particularly amoxicillin containing antibiotics. Third, we did not take into consideration if a child had either a past failure or an allergy to penicillin, which could influence what type of initial antibiotic was prescribed. Fourth, as the study population was limited to commercially insured children, it may be difficult to generalize to either noninsured or Medicaid populations. Further work should be done to characterize the patterns of antibiotic use in these populations. Fifth, our study was limited to dispensed prescriptions where a claim was filed to the insurance company. Antibiotics given as a free sample from a physician's office or through a pharmacy program giving free courses of generic antibiotics would not be captured, and thus we may have underestimated the actual amount of antibiotic use. However, it has been estimated that only 5% of children received free samples in 2004,Following the release of the initial AAP/AAFP guidelines, the practice of antibiotic dispensing appears to have initially decreased, followed by a rebound to pre-guideline levels. While the most recent estimates indicate antibiotic treatment may again be declining, overall use of antibiotics remains high. Additionally, we document an increasing use of cephalosporins for first-line treatment of AOM. This is discouraging in light of higher rates of treatment failure observed with cephalosporins. Overprescribing of antibiotics and use of non-amoxicillin therapy for AOM treatment are worrisome as these deviations from treatment guidelines could lead to the development and transmission of antibiotic-resistant infections.Appendix S1Codes for intravenous antibiotics included in the failure analysis.(DOCX)Click here for additional data file.


P seudonocardia bacteria, which (somehow) evolve new compounds in arms-race fashion against parasites. Alternatively, attines (somehow) selectively recruit multiple, non-coevolved actinobacterial genera from the soil, enabling a ‘multi-drug’ strategy against parasites. We reconcile the models by showing that when hosts fuel interference competition by providing abundant resources, the interference competition favours the recruitment of antibiotic-producing (and -resistant) bacteria. This partner-choice mechanism is more effective when at least one actinobacterial symbiont is vertically transmitted or has a high immigration rate, as in disease-suppressive soils.There is great interest in explaining how beneficial microbiomes are assembled. Antibiotic-producing microbiomes are arguably the most abundant class of beneficial microbiome in nature, having been found on corals, arthropods, molluscs, vertebrates and plant rhizospheres. An exemplar is the attine ants, which cultivate a fungus for food and host a cuticular microbiome that releases antibiotics to defend the fungus from parasites. One explanation posits long-term vertical transmission of  We know it works in practice, but does it work in theory?-An old joke about bureaucrats and economistsExplaining how microbiomes are established and maintained is now one of the leading questions in biology and has attracted investigators from molecular biology to community ecology to evolutionary game theory . Host spIt can be useful to think about microbiome biology as a branch of community ecology , just withe environment is itself a host species that evolves, potentially in ways that affect the composition of the microbiome. Not surprisingly, there is evidence that gut microbiome composition is governed by host species , according to each symbiont's type.To model the coevolution of host and microbiome, et al. Our purpose here is to identify conditions under which hosts can successfully ‘screen-in’ microbiomes that are dominated by antibiotic-producing (and -resistant) bacteria, of which there is a fast-growing number of examples, ranging across arthropods , plant rhizospheres, marine corals, sponges, cone snails and even the hoopoe bird , which is by far the best studied of its kind  are true mutualists, having coevolved and codiversified with the attine ants via vertical transmission, with rare recruitment across ant lineages or from the environment  by providing the right level and mix of resources to fight over. Consistent with this scenario, Pseudonocardia strains isolated from attine colonies fight each other in vitro  hosts can confer competitive superiority on antibiotic-producing (and -resistant) bacteria by providing high levels of resources, and that (2) such microbiomes exhibit priority effects, so fixation of antibiotic-producers in the microbiome is more likely if antibiotic-producers are more abundant than non-producers at initial colonisation. Thus, vertical transmission of one antibiotic-producing lineage (or a higher rate of immigration from the environment) can promote the horizontal recruitment of other antibiotic-producing species, thereby reconciling the two competing theories of the attine cuticular microbiome.S), beneficial microbes (B), antibiotics (A) and pathogenic microbes (P). B and P can represent individual species or functional groups of bacteria, and the terms are used to differentiate antibiotic producers from non-producers respectively. Pathogens are therefore parasitic in the sense that they consume host resources but provide no benefits, thereby imposing opportunity costs on the host. Note that Beneficials are always resistant to their own antibiotics, or antibiotic production would be suicidal, and Beneficials are typically also resistant to many antimicrobials that they do not themselves produce  (which must be a monotonously decreasing function) measures the effect of antibiotics on the Pathogen's net growth rate; K is the half-saturation constant for the Monod equation used to limit the growth of Beneficials as a function of nutrient concentration; δ is the decay or mortality rate. We assume a minimum dosage effect in f(A) (rP: in f(A)  to scaleAc is the concentration at which antibiotics halve the growth rate, and where A to be substituted by B. .where s = 1−b−p, and the non-trivial nullclines  If Beneficials have a higher growth rate, they competitively exclude Pathogens, even when there is no antibiotic production and regardless of the amount of host resources. This might occur if the host provides a substrate that is mainly available to Beneficials (‘private resources’) or simply by chance difference in growth rates. (2) If we assume, more realistically, that Beneficials have a lower growth rate than some Pathogens, Beneficials can never invade a population dominated by those faster-growing Pathogens. (3) However, as Beneficials divert increasing amounts of host resources to antibiotic production, which is a form of interference competition, the community begins to exhibit priority effects : neither Pathogen nor Beneficial can invade a population already dominated by the other. Instead, there are two stable equilibria: complete dominance by Beneficials or by Pathogens. Which equilibrium is reached depends on which bacterial type has the higher initial abundance. Dominance by Beneficials therefore requires both a sufficiently high per capita production of antibiotics and a sufficiently high initial Beneficial population density, which together create enough total antibiotic to fend off Pathogens.We now add competition-based screening by the host. Although antibiotic production may confer competitive superiority for the attine-ant niche (Appendix S1), antibiotic production is costly. One possibility therefore is that the host evolves to provide high levels of resources (i.e. higher than in the soil), which can be used to fuel antibiotic production by Beneficials. In fact, it turns out that even when host-supplied resources are assumed to be equally available to both Pathogens and Beneficials (a ‘common-pool resource’), the competitive landscape can still favour Beneficials as long as interference competition is sufficiently strong (i.e. the antibiotics are sufficiently effective).Is on the dynamics of the microbiome model, again conservatively let Beneficial growth rate be less than Pathogen growth rate, rb < rp. If there are no Beneficials in the microbiome, b = 0, the nullcline of the Pathogen is above the nullcline of the Beneficial, and the Beneficial cannot invade a population of pathogens. However, if Beneficials are present, b > 0, increasing host resource provision, Is, steepens the nullcline for the pathogen, eventually causing the system to become bistable  and assume that there are non-zero immigration rates The effect of bistability is that it is possible for a host to screen-in a microbiome dominated by Beneficials, even if host-provided resources can be consumed by all bacterial types and even if Pathogens have higher intrinsic growth rates. This process can be broken down into three steps: (1) the new host's microbiome starts with a higher proportion of Beneficials, which can be achieved via vertical transmission or via a higher immigration rate of Beneficials due to, for instance, spatial aggregation of previously successful hosts or benign environments (e.g. ‘disease-suppressive’ soils), and (2) the host provides a high resource level, which (3) fuels intense interference competition via antibiotic production and results in competitive dominance by Beneficials.We have used a phenomenological model to combine stylised facts about one type of microbiome with some simple ideas from game theory (screening) and community ecology (interference competition) to argue that it is possible for hosts to evolve living conditions under which antibiotic-producing bacterial species have a competitive advantage in the host niche.High general resource availability can favour Beneficials in competition over Pathogens, because even though abundant resources fuel higher growth rates for all bacteria, some of those resources can also be diverted by Beneficials to produce antibiotics . There iHowever, for Beneficials to win, there additionally needs to be a sufficient number of Beneficials at the start of competition, so that enough total antibiotics are produced to kill off faster-growing but susceptible competitors. This problem manifests in the model as bistability, which appears generally in models of species competition with interference competition . VerticaAlthough we focused on the problem of partner choice in mutualisms, another evolutionary challenge is social conflict between Beneficials (B) (antibiotic-producers and antibiotic-resistant) and ‘Cheaters’ (C) (non-producers but still antibiotic-resistant). If we allow that B produces a public good for all resistant strains, which is a costly act, then C should always outcompete B, and antibiotic production should disappear. How is cooperation amongst B (antibiotic production) maintained if C has a fitness advantage?This is the classic problem of public goods evolution, and multiple mechanisms can prevent cheaters from winning over cooperators. The two most likely to be important in microbiomes are as followsBacteria generally grow on surfaces with restricted dispersal. This limited mixing results in the positive assortment of cheaters and cooperators, meaning that any given bacterial type is more likely to be neighbours with the same type. Consequently, the average benefit of C decreases, and the average benefit of B increases. The strength of this effect depends on the frequency of types, but in general, C does not drive B extinct  in our model].A more general mechanism is that if the public good is not a ll mixed . Most biThus, the apparent evolutionary advantage of a C over a B happens only when (1) there is no assortment, and (2) the public good is linear. The absence of both conditions is unlikely in biological systems. As an aside, the parameter governing the level of investment in antibiotic production, α, should be seen as the mean level of investment, allowing some individuals to invest more and others to invest less or nothing.Returning to the attines, we conclude that competition-based screening can describe the evolutionary ecology of the attine cuticular microbiome. First, high resource provision by attine hosts is a reasonable assumption, given the presence of specialised glands  stochasticity in the initial microbiome composition such that only incipient cultivars with high-enough Beneficials frequency survive to assemble an actinobacteria-dominated microbiome, (2) spatial aggregation of or simply interactions between successful Atta colonies, leading to a higher initial immigration Ib of Beneficials (Interestingly, the cuticular microbiome in the most derived attine genus, eficials , and/or eficials , which cAtta's ecological dominance is that the non-trivial cost of supporting a protective microbiome, if such a microbiome indeed exists in Atta, has moved down a trophic level to the cultivar, which would not only increase efficiency but also free Atta to invest more in metapleural gland secretions (We speculate that one reason for Screening can be a somewhat non-intuitive concept. It might help to point out that, unlike with costly signalling, a screening host never needs to detect the qualities of the potential symbionts, nor does the host choose amongst symbionts. Instead, the pool of potential symbionts is placed under selection to colonise or not colonise the host environment, over evolutionary and ecological timeframes, or, under competition-based screening, the symbionts themselves exclude undesired species and genotypes in ecological time (We stress that screening is only one cooperation-enforcement mechanism. Screening can solve the problem of hidden characteristics, but other mechanisms are needed to solve hidden-action and public-goods problems, all of which can arise within a single mutualism (Is* and that Beneficials evolve to an optimal, positive α* once Is evolves to a level high enough that the P–B system is bistable.We also emphasise that do not explicitly model host-symbiont coevolution and the origin of antibiotic-producing microbiomes. It remains an open challenge to explain how hosts evolved to provide costly resources to a microbiome. One scenario is that a simple actinobacterial microbiome originated via vertical transmission, and, later, specialised microbial parasites and possibly reduced antibiotic efficacy selected for hosts that provided high levels of resources, which would immediately increase antibiotic production and recruit multiple antibiotic-producing bacteria. In the Supplementary Information, we explore the evolution of a host that reacts to increased Pathogen levels by increasing resource provision, which can be interpreted either as the above scenario or simply as the evolution of increased efficiency in the host. Another origins scenario is that antibiotic-producing but non-mutualistic bacteria had a competitive advantage for the ant niche, which is assumed to have originated as a low-resource environment. However, mutant hosts providing higher resource levels would have resulted in greater antibiotic production, which would be available to use for protection of the ant's fungal cultivar. Vertical transmission could evolve secondarily. We also show in Supplementary Information that the host evolves to an optimal positive resource supply in vivo (Testing for screening poses challenges . Antibio


However, the factors that determine the fraction of resistant cells in the bacterial population remain unclear, indicating a fundamental gap in our understanding of how antibiotic resistance evolves. Here, we experimentally track the spread of a plasmid that encodes a β-lactamase enzyme through the bacterial population. We find that independent of the initial fraction of resistant cells, the population settles to an equilibrium fraction proportional to the antibiotic concentration divided by the cell density. A simple model explains this behavior, successfully predicting a data collapse over two orders of magnitude in antibiotic concentration. This model also successfully predicts that adding a commonly used β-lactamase inhibitor will lead to the spread of resistance, highlighting the need to incorporate social dynamics into the study of antibiotic resistance.Inactivation of  A frequent mechanism of antibiotic resistance involves the production of an enzyme that inactivates the antibiotic . The acqPrevious studies have provided valuable insight into the evolutionary processes that govern the spread of antibiotic resistance . HoweverE. coli bacteria with an isogenic strain containing an additional plasmid encoding a β-lactamase enzyme. The enzyme hydrolytically inactivates the antibiotic   . While tant (KM)  and 2C aant (KM) .fR, on the initial antibiotic concentration, Ai, and initial cell density, Ni. The model predicts that the equilibrium fraction scales in the following manner:We obtained an exact analytic solution of this model that describes the dependence of the equilibrium-resistant fraction, This relationship is surprisingly insensitive to many parameters, including the length of the lag phase, rate of cell death, and cost associated with resistance . In partR=1.1/h; S/γR=1.15; S−γR=∼0.17/h), which includes the cost of plasmid maintenance, of expressing the β-lactamase enzyme, and of expressing a red-fluorescent protein used for tracking the resistant fraction , and KM=6.7 μg/ml. This MIC is slightly lower than our measured value . Indeed, a plot of the equilibrium density of resistant cells against the antibiotic concentration revealed a striking collapse of the data extending over two orders of magnitude in the antibiotic concentration , where [I] and KI are the inhibitor concentration and dissociation constant, respectively. As the equilibrium fraction increases linearly with KM, the model predicts that it should also increase linearly with the inhibitor concentration [I]. To probe this predicted dependence of the equilibrium fraction on the inhibitor concentration, we measured the equilibrium fractions from maps of difference equations obtained at varying tazobactam concentrations  was well within the literature values , the addition of sulbactam can lead to the accelerated spread of resistant bacterial cells in a range of clinically relevant antibiotic concentrations  the presence of a metabolic cost associated with being resistant, and (2) the inactivation of the antibiotic by resistant cells. When both features apply, our model suggests that resistant and sensitive cells may coexist at high concentrations of the antibiotic, with the fraction of resistant cells approximately proportional to the antibiotic concentration divided by the cell density. We found that this simple dependence on antibiotic concentration and cell density successfully predicts the equilibrium fraction of resistant cells over two orders of magnitude in antibiotic concentration .This model not only agrees quantitatively with experimental data, but it also provides insight into the conditions that enable coexistence between resistant and sensitive cells. For example, a recent study observed coexistence with a mutated β-lactamase enzyme that inactivated the antibiotic outside the cell , allowinThe interplay between initial cell density and antibiotic concentration is often important in determining growth dynamics in antibiotics . LikewisOne might worry that our conclusions may be limited to laboratory strains as natural strains would be better adapted to plasmids found in the wild. However, our model and experiments argue that the equilibrium fraction depends only weakly on the fitness cost of carrying the resistance plasmid . CompensWithin the framework of our model an important qualitative difference between using a bactericidal versus a bacteriostatic antibiotic is that the overshoot of the resistant fraction above the equilibrium fraction should only appear when using a bactericidal antibiotic . The lowThroughout our experiments, we limited ourselves to antibiotic concentrations that do not affect the growth of resistant cells. However, at high enough concentrations, a bactericidal antibiotic may lead to lysis of resistant cells and the subsequent release of their β-lactamase enzymes into the extracellular space . Since tUnderstanding how the fraction of resistant bacteria changes with time is a central goal in studying antibiotic resistance. This already difficult task is further complicated by cooperative behaviors that allow resistant microbes to ‘share’ their resistance with the rest of the bacterial population. The cooperative nature of antibiotic inactivation causes the fitness of resistant cells to decrease as their fraction in the bacterial population increases  were diluted by a factor of 100 × and co-cultured at different fractions in 96-well plates containing LB and 5 μg/ml of kanamycin for another 23 h to synchronize the growth state of both strains  together with antibiotics for selection for 23 h. The saturated cultures (corresponding to a density of ∼10ains see . All comains see . In addiains see . Fractioains see .


Staphylococcus aureus, SL-tetracycline combination achieved total inhibition before 4 h of exposure while tetracycline alone couldnot achieve total inhibition till the end of 6 h. The inhibition caused by exposure of bacterium to SL-tetracycline mixture was ~25% more as compared to SL alone. In spite of known robustness of gram-negative bacteria, SL-cefaclor mixture proved to be efficient against Escherichia coli which showed ~48% more inhibition within 2 h of exposure as compared to cefaclor alone. Scanning electron microscopy of the cells treated with mixture revealed bacterial cell membrane damage and pore formation. Moreover, SLs being a type of asymmetric bola, they are expected to form self-assemblies with unique functionality. This led to the speculation that SLs being amphiphilic in nature can span through the structurally alike cell membrane and facilitate the entry of drug molecules. Sophorolipids (SLs), biosurfactants with antimicrobial properties, have been tried to address the problem of antibiotic resistance. The synergistic action of SL and antibiotics was checked using standard microdilution and spread plate methods. With  The advent of antibiotics for treating bacterial infections is considered as one of the major advances in modern medicine . Owing tIn this scenario, it is imperative to discover fresh antimicrobials or new practices that are effective for the treatment of infectious diseases caused by drug-resistant microorganisms . Staphylococcus aureus, clinicians have increasingly turned to multi antibiotic therapies  of the expected forms of SLs. Four different forms of Oleic acid derived SLs were detected. Diacetylated lactonic SL of Oleic acid, that is, 17-L-(-oxy)-octadecanoic acid 1,4′′-lactone 6′,6′′-diacetate, was detected with maximum % abundance. Diacetylated acidic form, monoacetylated lactonic SL, and monoacetylated acidic SL were also detected in relatively small proportions. Apart from Oleic acid derived SLs, different SL structures having Linoleic (C18:2), stearic (C18:0), and palmitic (C16:0) acids as the hydrophobic part were also detected. (Refer to supplementary information for mass spectrum.) The finding was in accordance with previous reports [ Prominent peaks from the mass spectrum were correlated to sodium adducts [M reports . Dengle-Pulate et al., 2013 have synthesized SL using Lauryl alcohol as hydrophobic precursor and assessed its surface tension reducing property along with the SL derived from Oleic acid (SLOA) as a control. They have reported the Critical Micelle Concentration value of SLOA as 0.12 g/L and lowest surface tension as 34 mN/m .S. aureus (ATCC-29737) was found to be 150 μg/mL, while that of SL was found to be 400 μg/mL. Therefore it can be observed that both SL and tetracycline are capable of achieving inhibition. In order to rightly assess the time dependent trend of inhibitory effect of combination, sublethal concentrations of SL (300 μg/mL) and tetracycline (15 μg/mL) were exercised during the assay. The time dependent bacterial inhibition on the action of SL and tetracycline has been represented in S. aureus at 300 μg/mL and showed total inhibition within 4 h. However, it was worth noting that when both agents were used in combination, at 2 h exposure ~22% more inhibition was observed.MIC of tetracycline against E. coli (ATCC 8739) was found to be 200 μg/mL, while SL alone was not inhibitory to E. coli till 1000 μg/mL. For the assay of conjugative effect, sublethal concentrations of SL and cefaclor were decided to be 500 μg/mL and 50 μg/mL, respectively. E. coli. Cefaclor achieved almost total inhibition at the end of 6 h exposure. SL alone was unable to totally inhibit the bacterial growth, but when administered along with the antibiotic, it resulted in faster killing of the bacterium. It is worth to be noted that SL-cefaclor together could achieve ~98% killing within 4 h, while with cefaclor alone it required 6 h exposure to get equivalent effect. MIC of cefaclor against It has been observed through previous reports that SLs have better antibacterial action against gram-positive bacteria as compared to that against the gram-negative ones. Sleiman et. al., 2009, have checked the action of SLs and SL derivatives against different clinically relevant bacteria and reported that some activity was found against gram-positive bacteria, but against gram-negative bacteria considerably high concentrations showed trace activity . Shah etS. aureus cells treated with the tetracycline-SL mixture, while E. coli cells treated with the cefaclor-SL mixture. Damage to cell membrane is evident from the images. The consequences of disturbed cell membrane integrity such as formation of membrane pores leading to leakage of cytoplasmic contents and accumulation of cell debris were also noted.Till date, no studies have evaluated the use of SLs in combination with antibiotics. Hence it is not known if these compounds might have antagonistic or synergistic effects when administered with antibiotics . We haveS. aureus and E. coli were used to evaluate the synergistic action of SLs with different antibiotics. These organisms are commonly occurring pathogens. S. aureus is a gram-positive coccus, currently responsible for the majority of skin and soft tissue infections (SSTIs) as per survey report carried out in the United States. This bacterium is commonly found asymptomatically in healthy individuals, colonizing the anterior nares and other sites of the body, such as the skin and gastrointestinal tract. However, S. aureus can be extraordinarily pathogenic, causing a broad range of morbid states from serious skin infections, such as cellulitis and abscesses, to endocarditis and sepsis. S. aureus is rapidly evolving resistance to contemporary topical as well as systemic antibiotics [E. coli is found in the lower intestine of warm blooded animals. E. coli is more than just a harmless intestinal inhabitant; it can also be a highly versatile pathogen that can be frequently deadly. Several different E. coli strains cause diverse intestinal and extraintestinal diseases by means of virulence factors that affect a wide range of cellular processes [In this study, ibiotics . Anotherrocesses . To inclThe scanning electron micrographs exhibit a range of morphological changes suggestive of damage to cell membrane, and the consequences of disturbed cell membrane integrity such as formation of membrane pores leading to leakage of cytoplasmic contents and accumulation of cell debris were noted. It should be noted that though the antibiotics differ in their action, similar features of cellular damage were observed in both cases. So it can be said that the inhibitory action involved cell membrane lipid order perturbation in addition to the action of antibiotic. The inhibitory effect of antibiotics was observed at lower concentrations when coadministered with SLs. Probably SLs have enhanced the drug action by facilitating the entry across cell membrane thus achieving requisite intracellular antibiotic concentration at low dosage. A hypothesis has been proposed about the entry of antibiotic molecules in presence of SL as schematically represented in Hypothesis about Mechanism of Drug Entry Facilitation by SLs. Naturally evolution does not provide any active transporter for antibiotics, and a passive diffusion process facilitated by channels must be invoked [ invoked . Antibio invoked . The out invoked . Tetracy invoked . TherefoE. coli. But in case of cells treated with the combination of SL and cefaclor, total inhibition was achieved much faster as compared to the sample treated with cefaclor alone. Therefore it can be concluded that the enhanced inhibitory effect is not due to additive action of two antimicrobial agents. Hence the enhanced efficiency of cefaclor-SL combination against E. coli can be considered as a proof for the argument that better performance is due to facilitation of entry of drug molecules by SLs.The SLs, as described earlier, are capable of forming micelles, bilayer structures, and self-assemblies which can enclose the water soluble drugs. When administered together, SLs can span through the structurally alike cell membrane lipid bilayer and deliver the drug molecules to the cell interior. Structural studies of SL-antibiotic mixture with sophisticated instrumentation may throw some light on interaction of the two such as micellarization. SLs are known to have better antibacterial action against gram-positive bacteria, while large doses of the SLs are required to demonstrate any antibacterial activity, especially with Gram-negative bacteria , 27. In Lactonic SLs have been reported to have better surface tension lowering and antimicrobial activity as compared to the acidic form . TherefoLactonic SLs are more hydrophobic as compared to the acidic SL. Packing constraints are associated with the lactonic SLs due to closed-ring structure of alkyl chain. Self-assembled structures of lactonic SLs can be unilamellar vesicles or tubules, whereas acidic SLs generally form small globular micelles. Therefore pertaining to the hypothesis we have speculated about the entry of drug molecules, it can be said that varying the lactone: acid percentage will also affect the affinity of micellar structures towards water soluble and water insoluble drugs .Combined antibiotic therapy has been shown to delay the emergence of bacterial resistance and also produce desirable synergistic effects in the treatment of bacterial infections . In caseThe structure of the surfactant dictates the HLB, that is, hydrophilic lipophilic balance value of the molecule. This value indicates whether the molecule will form water in oil, that is, W/O emulsions, or oil in water, that is, O/W emulsions. Depending on the solubility of the antibiotic, choice of surfactant can be made. SLs are known as “tailor-made molecules.” It is possible to achieve SL structural variation by varying the hydrophobic or hydrophilic carbon substrates fed during the synthesis procedure. Therefore due to enhanced entry and simultaneous action of 2 inhibitory agents, it can be expected that the coadministration of suitable SL and antibiotic will handle the infection efficiently. SLs can be safely administered till considerably high dosage, that is, 5 mL/kg of body weight, which is another fact favouring its pharmaceutical usage . Coadministration of SL enhanced the action of antibiotics in representative gram-positive and gram-negative bacteria. These bacteria differ in their cell membrane structures and also the machinery to prevent the entry of antibiotic molecules. Considering the ability of SLs to form self-assemblies it has been speculated that self-assembled SLs can span through the structurally alike bacterial cell membrane and thus facilitate the entry of drug molecules. Self-assembled system may enhance solubility of antibiotic or offer shielding from the environment hence resulting in improved efficiency. Additionally SLs are antimicrobial in nature. Hence, if co-administered with another inhibitory agent, the mixture reduces the likelihood of bacterial survival and probably the development of resistance as the bacteria have to combat against 2 agents.The supplementary information contains (a) Dilution scheme for the assay of conjugative action of Sophorolipid and cephaclor against E. coli. The dilution scheme is similar to the one represented in Table 1. (b) HPLC chromatogram of the crude sophorolipid preparation which puts some light on the relative lactone: acid percent composition of the crude sophorolipid. (c) MALDI/MS spectrum of the sophorolipid preparation in which the peaks corresponding to prominent forms of oleic acid derived sophorolipid have been marked with arrows. Along with oleic acid derived sophorolipid, few more SL forms containing other fatty acids as hydrophobic tail have been listed in a table.Click here for additional data file.


The overall volume of antibiotic consumption in the community is one of the foremost causes of antimicrobial resistance. There is much ad-hoc information about the inappropriate consumption of antibiotics, over-the-counter availability, and inadequate dosage but there is very little actual evidence of community practices.This study surveyed antibiotic use in the community (December 2007-November 2008) using the established methodology of patient exit interviews at three types of facilities: 20 private retail pharmacies, 10 public sector facilities, and 20 private clinics to obtain a complete picture of community antibiotic use over a year. The Anatomical Therapeutic Chemical (ATC) classification and the Defined Daily Dose (DDD) measurement units were assigned to the data. Antibiotic use was measured as DDD/1000 patients visiting the facility and also as percent of patients receiving an antibiotic.During the data collection period, 17995, 9205, and 5922 patients visiting private retail pharmacies, public facilities and private clinics, respectively, were included in our study. 39% of the patients attending private retail pharmacies and public facilities and 43% of patients visiting private clinics were prescribed at least one antibiotic. Consumption patterns of antibiotics were similar at private retail pharmacies and private clinics where fluoroquinolones, cephalosporins, and extended spectrum penicillins were the three most commonly prescribed groups of antibiotics. At public facilities, there was a more even use of all the major antibiotic groups including penicillins, fluoroquinolones, macrolides, cephalosporins, tetracyclines, and cotrimoxazole. Newer members from each class of antibiotics were prescribed. Not much seasonal variation was seen although slightly higher consumption of some antibiotics in winter and slightly higher consumption of fluoroquinolones during the rainy season were observed.A very high consumption of antibiotics was observed in both public and private sector outpatients. There was a high use of broad spectrum and newer antibiotics in the community. Suitable and sustainable interventions should be implemented to promote rational use of antibiotics that will help in decreasing the menace of antibiotic resistance. The current worldwide increase in antimicrobial resistance (AMR) and, simultaneously, the downward trend in the development of new antibiotics have serious public health and economic implications. The increased resistance is a result of many factors, but the foremost cause is the overall volume of antibiotic consumption. About 80% of antibiotics are used in the community and the rest are used in hospitals ,2. It isIn collaboration with the World Health Organization (WHO) a pilot project was conducted in New Delhi, India (2002-2005)  and elseSurveillance of antibiotic use was done by collecting data from four municipal wards  of New Delhi, India. The study was done in conjunction with another study (not described here) to measure the antimicrobial resistance pattern for the OPD patients of a private tertiary care hospital located in West Delhi. Hence, the antibiotic use data was collected from four municipal wards around this hospital - the same 4 wards as used in the previous study in private retail pharmacies . The fouBoth the public and private sectors were included in the survey. Medicines are provided free of charge to patients in public sector facilities but must be paid for in private sector facilities. In order to get a complete picture of antibiotic use in the community, three different types of facilities were chosen:1. Public sector - All 10 facilities under the Government of National Capital Territory of Delhi (GNCT Delhi) in our catchment area were enrolled for the survey. The facilities were 8 dispensaries (Primary care facility) and 2 hospitals (Secondary care level);2. Private retail pharmacies - A total of 185 licensed private retail shops were located in the four chosen municipal wards from which 20 well-stocked, private retail shops, willing to cooperate, were chosen for the study;3. A total of 20 private sector doctors, who were willing to cooperate for the study and were practicing in the chosen areas, were chosen and consisted of 4 paediatricians, 3 physicians, 12 general practitioners (GPs), and 1 dermatologist .A convenience sample for private sector facilities was used because many doctors and retail pharmacy shops do not tolerate continued data collection processes. Moreover we wanted to include facilities with a sufficient number of patients per day. A good liaison was maintained with all the participants and their professional associations, who helped in enrolling the facilities throughout the study period.Trained data collectors (pharmacists) collected antibiotic use data by conducting exiting interviews with all patients receiving/purchasing an antibiotic on leaving the facility. For private retail pharmacies any patient purchasing an antibiotic, whether with a prescription, without a prescription, or on the advice of chemist, was interviewed. For public sector facilities and private clinics all the patients interviewed were out-patients. In private facilities, exiting patient interviews were conducted in a part of the waiting room after the patient had left the consultation room. In pharmacies, exiting patient interviews were conducted in a part of the shop or on the street outside. At public facilities, exit interviews were conducted near the pharmacy of the same facility. A pre-designed proforma was used to collect data regarding the name of the antibiotic, the strength, the dose and the number of units prescribed by the doctor, and the number of units dispensed or purchased.30 exit interviews were conducted in each public sector facility and private retail pharmacy in each month. However, only about 10-12 exit interviews were conducted in each private clinic every month as the patient flow was much less and it was not possible to wait the required time to collect the same number of patients due to resource constraints. The rationale for conducting this number of exit interviews is from the WHO manual, "How to investigate drug use in health facilities" which recommends 600 encounters (20 facilities and 30 patients/prescriptions per facility) for one survey [The Anatomical Therapeutic Chemical (ATC) classification and the Defined Daily Dose (DDD), ATC/DDD (2006), measurement units were assigned to the data . ConsumpAll the data collected was entered into software developed in Visual Basic, SQL Server and Crystal Reports. The same software was used to analyse the data.Ethical approval for the study was obtained from Vallabhbhai Patel Chest Institute, University of Delhi, India and also from WHO Ethics Review Committee. Informed consent was obtained from all participants and facilities involved in the study.In enrolled private retail pharmacies, 7101 patients (39.5%) out of 17995 patients visiting the pharmacies during data collection purchased an antibiotic (and were thus interviewed). In enrolled public facilities, 3615 (39.3%) out of 9205 patients were prescribed an antibiotic. In enrolled private clinics, 2571 (43.4%) out of 5922 patients were prescribed an antibiotic.Table Table Table At public facilities, while the newer members from each class of antibiotic were also used, there was more use of the older antibiotics than in the private sector. Thus, newer antibiotics such as cefuroxime, ofloxacin, and roxithromycin were commonly used as in the private sector but older antibiotics such as cephalexin, erythromycin, cotrimoxazole, and tetracyclines were also commonly used. However, older antibiotics were used sparingly in the private sector Table . For penFigures This is one of the first studies from a developing country that describes a large, comprehensive surveillance of antibiotic use in three facility types over a one-year period to get a complete picture of antibiotic use in an urban community. There is evidence at the national level  as well Surveillance of antimicrobial use in the community for developing countries is difficult because no databases are available and antibiotics can be purchased over-the-counter ,15. The Measuring the percent of antibiotic containing prescriptions is an easy and more reliable method than measuring the DDD/1000 inhabitants in these settings as the data is not collected from all the facilities serving a population. However, data on DDD consumed per 1000 patients can help in providing insight into how antibiotics are used . For exaThe surveillance system was able to track trends and patterns of antibiotic use in all the types of facilities: public facilities, private clinics and private retail pharmacies. Findings from the present survey clearly show the importance of tracking antibiotic use in different facility types as consumption of various classes of antibiotics was clearly different. In the public sector, almost all classes of antibiotics were prescribed while in the private sector virtually only the newer antibiotics were consumed. Comparison of the results of this survey in 2008 with the pilot survey conducted at the private retail pharmacies in the same areas in 2004 [No major differences in the pattern of use of the various antibiotic groups were found between the four wards/areas surveyed for any facility types nor were any major differences found with regard to the percent of patients receiving antibiotics in four areas surveyed. In each of the four areas, the percent of patient receiving an antibiotic was 38%-41% in public facilities and 39%-41% in private retail pharmacies. However, for private clinics the percent of patients who received antibiotics in Rajouri Garden was 34% and in Karol Bagh 38% as compared to Patel Nagar where it was 56% and Rajinder Nagar where it was 50%. It is difficult to determine the reasons for this variation but it may be associated with the general socioeconomic status of the neighbourhoods, as Patel Nagar and Rajinder Nagar are richer than the other areas. As we did not study the sociodemographic profile of the patients visiting the facilities it is not possible to analyse this further. A study conducted in Uttar Pradesh, India showed that higher socioeconomic status of the patients was associated with higher antibiotic use .A small degree of variation was observed in the prescription of different antibiotics over 12 months. In public facilities any variation could have been due to variation in supply of antibiotics to public health facilities from the main central store (though correlation of use with availability was not done). Overall there did appear to be slightly greater use of antibiotics  used for acute respiratory tract infections (ARI) in the winter months and for antibiotics used for diarrhea (fluoroquinolones) in the humid summer months. A survey conducted simultaneously with this study showed that number of diarrhea cases did increase during the rainy summer months and that fluoroquinolones were the most commonly prescribed antibiotic for diarrhea . It is lThe high and increasing use of the newer antibiotics in the community is worrying, as such antibiotics may often not be needed and their use will lead to resistance in the treatment of serious infections. The older antibiotics should be sufficient for many of the common infections seen in the community. While there is a profit-motive in the private sector for using the newer and more expensive antibiotics, the reason for their increased use in the public sector is not clear. There is an essential medicine list (EML) for all public facilities under the Government of National Capital Territory of Delhi, and this list is regularly updated and used for procurement of all medicines. The Delhi state EML has a separate EML for dispensaries and this list has antibiotics, like amoxicillin, ampicillin, ciprofloxacin, norfloxacin, cephalexin (for restricted use), erythromycin, roxithromycin, cotrimoxazole and doxycycline. These antibiotics are the first choice to treat most common infections in the community. Antibiotics like ofloxacin and cefuraxime are added to the hospital list of the EML with an *asterisk indicating that they are reserve antibiotics to be used only in case of significant resistance to other antibiotics . HoweverOur study has successfully captured the pattern of antibiotic use in the community. We did not measure DDD/1000 inhabitants as is generally done by studies in European countries. In our settings this is not an accurate measure of exposure of the population to antibiotics because we have not included all the facilities of our catchment area and complete data  could not be collected from any enrolled facility. The objective was not to measure accurately population exposure to antibiotics, but rather to measure trends in use as part of a surveillance system. Provided the same methodology is used each month, the same degree of error will occur each month and the data collected will be sufficient for trend measurement even though it is not accurate for a one-off exposure measurement. Since the exit interview data only measures use in some of the patients attending some of the health facilities, the total number of DDDs per population would be much less than would be the case if all the facilities were included.The most important strength of the study is that it clearly shows that it is possible to collect useful data for antibiotic use in all types of facility from wherever it is prescribed/dispensed/purchased, at the individual patient level in resource-constrained settings. The study has some inherent weaknesses. Firstly, it was conducted in four residential localities of one urban area, so generalization should be done with caution for the rest of Delhi and cannot be done for other areas of India. Secondly, the presence of data collectors may have changed the prescribing and dispensing habits of doctors and retailers. Doctors may have prescribed fewer antibiotics than normal and retailers may not have dispensed antibiotics over-the-counter as often as normal. Some of the Hawthorn effect may have reduced over the period of one year, as the health workers got used to the presence of the data collectors. In public facilities, the bias on doctors' prescribing may have been less as the data collectors were in the pharmacy area and doctors were not always aware which day and time data collectors were visiting. The reduced sample size of exiting patient interviews in private sector clinics, due to time and resource constraints may have resulted in less accurate estimates of antibiotic use in this facility type as compared to the other facility types. However, the year-long duration of the study should partially compensate for the lesser number of patients interviewed each month. While the methodology used is simple, reproducible, and feasible for collecting data from various facilities in the community over a long period of time, it requires attention to detail particularly with regard to supervision of data collection, data management and maintaining good relations with frequent feedback to participating facilities (in order to maintain their cooperation).Antibiotic use is the key driver of antimicrobial resistance. Antibiotics are overused, particularly for minor infections, misused for self-limiting viral infections and underused due to financial concerns. Extensive surveillance programmes have been used to study patterns of antibiotic resistance and use in developed countries. These systems have made it possible to stimulate the implementation of nationwide interventions to improve antibiotic use . ResultsThe authors declare that they have no competing interests.Both the authors (AK and KH) are responsible for the reported research, and have participated in the concept and design, analysis and interpretation of data, revising of the manuscript, and have approved the manuscript as submitted. AK was also responsible for getting data collected from different public and private facilities, data entry, and drafting the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/11/99/prepub


PubMed is a free web literature search service that contains almost 21 millions of abstracts and publications with almost 5 million user queries daily. The purposes of the study were to compare trends in PubMed-indexed cancer and biomedical publications from Egypt to that of the world and to predict future publication volumes.The PubMed was searched for the biomedical publications between 1991 and 2010 (publications dates). Affiliation was then limited to Egypt. Further limitation was applied to cancer, human and animal publications. Poisson regression model was used for prediction of future number of publications between 2011 and 2020.Cancer publications contributed 23% to biomedical publications both for Egypt and the world. Egyptian biomedical and cancer publications contributed about 0.13% to their world counterparts. This contribution was more than doubled over the study period. Egyptian and world’s publications increased from year to year with rapid rise starting the year 2003. Egyptian as well as world’s human cancer publications showed the highest increases. Egyptian publications had some peculiarities; they showed some drop at the years 1994 and 2002 and apart from the decline in the animal: human ratio with time, all Egyptian publications in the period 1991-2000 were significantly more than those in 2001-2010 . By 2020, Egyptian biomedical and cancer publications will increase by 158.7% and 280% relative to 2010 to constitute 0.34% and 0.17% of total PubMed publications, respectively.The Egyptian contribution to world’s biomedical and cancer publications needs significant improvements through research strategic planning, setting national research priorities, adequate funding and researchers’ training. The size of the biomedical literature has grown exponentially over the past few years . The PubPubMed is a free Web literature search service and is the first choice first choice for electronically searching and retrieving biomedical literature. Almost 5 million queries are issued to PubMed each day by users around the globe , who relCancer is a major worldwide health problem being one of the four leading threats to human health and development . In 2008, more than 12 million people were diagnosed and more than 7 million people died of cancer. In 2030, these figures will nearly double. Almost, 55% of new cancer cases and 65% of cancer deaths occur in the less developed world regions, including Egypt .Egypt is one of the oldest civilizations in history and its contribution to human’s knowledge cannot be denied. Azhar is one of the oldest world’s universities that was settled in the 10th century and Cairo university being the current biggest Egyptian university was established in 1908 . Four EgThe aims of this study were to compare past trends in PubMed-indexed biomedical and cancer publications from Egypt to that of the entire world between 1991 and 2010 and to predict future trends in 2011 through 2020. The outcome of this study may alert researchers as well as decision makers in Egypt and similar countries to the current situation in biomedical and cancer research and the required level they should aim at.On the 25th of June 2011, the PubMed was searched using a methodology similar to that used in the literature ,17,18. TThe above steps were then repeated with the affiliations limited to Egypt “Egypt[affiliation]”. This allowed retrieval of Egyptian total, human and animal biomedical publications in the PubMed  as well as Egyptian total, human and animal cancer publications .Almost always, the total number of world’s publications was higher than the sum of its human and animal publications. This could be due to the presence of publications which could not be classified as animal or human . Occasionally, the total number of Egyptian publications was lower than the sum of its human and animal publications. We manually revised the PubMed ID of these publications. Almost always, some publications had the same PubMed ID being classified as both animal and human at the same time. When this was encountered, they were reviewed and classified appropriately and the number of human or animal publications was changed accordingly. This happened for Egyptian human and animal cancer publications for the years 1991, 1992, 1995, 1996, 1999, and 2003 where 4, 7, 11, 4, 15 and 18 publications were classified as both human and animal. All were allocated to animal and removed from human publications of the respective years. Thus the number of human publications in the mentioned years is smaller than that the PubMed figures by a factor equal to the duplicate publications.Analyses were done using SPSS® software version 15 and Microsoft® excel 2007. Categorical variables were presented as percentage and group differences were assessed using Chi squared test. Numerical variables were presented as means/medians and standard deviations (SD)/interquartile ranges (IQR) Why not range. Means and medians were compared using the t-test or the Mann Whitney U test, respectively. A probability (two-sided) equal to or less than 0.05 was considered statistically significant.The annual percent change (APC) was calculated by dividing the difference between the number of publications in a particular year and that of its preceding year by the latter and converting to a percentage. Considering the nature of the dependent variable (count of publications in the coming years), Poisson regression model was used for prediction of future number of publications between 2011 and 2020.Between 1991 and 2010, there were 11 644 346 world biomedical publications listed in the PubMed  of Egyptian biomedical publications to the worldwide PubMed publications was 0.13% (±0.04%). When classified into human and animal  and period 2 (2001-2010) Table . For perBetween 1991 and 2010, the annual percentage change (APC) of world biomedical publication ranged between -0.22% and 9.49% with a mean of 4.4% and a median of 3.95%. For the first (91-2000) and second (2001-2010) decades, the mean APCs were 2.94% and 6.03% while the median APCs were 2.43% and 6.17%, respectively. Also between 1991 and 2010, the APC of world cancer publications ranged between 2.02% and 8.34% with a mean of 4.82% and a median of 4.52%. For the first and second decades, the mean APCs were 3.88% and 5.93% while the median APCs were 3.90% and 6.00%, respectively. Between 1991 and 2010, the APC of Egyptian biomedical publication ranged between -5.79% and 22.53% with a mean of 9.75% and a median of 12.36%. For the first and second decades, the mean APCs were 4.81% and 13.28% while the median APCs were 4.55% and 15.06%, respectively. Also between 1991 and 2010, the APC of Egyptian cancer publications ranged between -45.59% and 45.74% with a mean of 12.94% and a median of 17.21%. For the first and second decades, the mean APCs were 12.48% and 12.93% while the median APCs were 13.21% and 21.65%, respectively.e (Y) = -74.322 + 0.044*χ} and {loge (Y) = -205.315 + 0.106*χ}, respectively. Assuming all conditions will remain the same, using these equations, the total world biomedical publications in 2020 are expected to mount to 857548 (95% CI: 855507-859595) publications with a 62.9% increase relative to 2010  = -88.510 + 0.050*χ} and {loge (Y) = -296.166 + 0.137*χ}, respectively. Assuming all conditions will remain the same, using these equations, the world cancer publications in 2020 are expected to mount to 271171 (95%CI: 269962-272386) publications with a 73% increase relative to 2010. The Egyptian cancer publications in 2020 are expected to mount to 1459 (95%CI: 1288-1654) publications with a 280% increase relative to 2010 . The same was true for world animal biomedical and cancer publications (~25% for both). While the Egyptian human biomedical publications remained constant at ~50% of the total, that for cancer increased slightly from 64% to 70%. Egyptian animal biomedical publications showed progressive decline from 41% in 1991 to 22% in 2010. The same was also noted for animal cancer publications (31% in 1991 and 22% in 2010). The reasons of decline in Egyptian animal publications are unknown. However, limited availability particularly of the special strains, higher costs, the relative lack of animal breeding and housekeeping facilities coupled with a possible vanishing interest in animal research can possibly explain for such observation. Nevertheless, this should be investigated and corrective actions be taken as animal research can significantly save humans.All types of world publications showed progressive increase with time. However this increase showed a higher pace starting the year 2003. The reason for this may be due to the progressive increase in research spending for life sciences particularly in the years 2001 and 2002 that is maintained thereafter . MoreoveEgyptian publications showed progressive increase that was slight till the year 2002 when the rise was marked. While this can reflect a true rise, it can also reflect more publications in PubMed-indexed journals. The decline in Egyptian publications in the years 1994 and 2002 followed periods of economical difficulties ,29 so thAssuming all current conditions remain the same, it is expected that Egyptian biomedical and cancer publications will increase at a pace higher than that of the world. This will represent a catch-up phenomenon as the Egyptian publications are currently very low. To increase Egyptian publications from the current 0.24% to the desired 1.2% of the world’s publication to match the Egyptian/world’s total population, several actions have to be taken. Researchers move to PubMed-indexed and online journals can have rapid effects. Providing technical help for the so many local journals to be indexed as well as available on the internet will be also of help. Research strategic planning and setting national research priorities  will be of great impact. Adequate funding of biomedical and cancer research with more participation of the private sector and the non-governmental organizations are eagerly needed. At the same time animal research needs to improve. Researchers’ training and awareness are of utmost importance. Setting animal breeding and housing facilities, importing and expanding unique animal strains will be of great help. Sharing equipment and adopting the concept of central research laboratories may also be of help.The current study has some limitations. It was limited to PubMed indexed publications and the search was done on 25th June 2011. Any PubMed search repeated on a later day may yield different results, typically higher, as NLM may have processed more completed citations for various reasons, e.g., time lag in receipt, or a new journal for indexing going back to volume 1, or data from back issues such as those deposited in PubMed Central, or from other sources  The 19 mUnequal indexing of publications by language and geography occurs across databases . The PubIn conclusion, despite that Egyptian publications had increased markedly from 1991 to 2010, yet its contribution to the world’s overall publications needs be leveraged to match Egypt’s value as the “Land of Civilization”. Several actions need to be taken to achieve the desired research volumes.The authors declare no competing interests; financial or otherwise.All authors contributed to the work significantly. The first two authors developed the concept, searched the PubMed, collected data and wrote the manuscript. The first and third authors performed the statistical analyses and performed the literature search. All authors read and approved the final manuscript.


Objectives. To assess participants' knowledge about HIV/AIDS and to identify the factors associated with HIV/AIDS in Sudan. Methods. Observational cross-sectional study carried out at Omdurman National Voluntary Counseling and Testing Centre, Sudan covered 870 participants. Sociodemographic data as well as information related to sexual behavior were collected. Results. Most of the respondents were knowledgeable about the true transmission modes for AIDS virus. Very few respondents knew someone infected with AIDS (4.5%), died of AIDS (8.1%), accepted to live with someone infected with AIDS (4.7%) or to work with someone infected with AIDS (2.1%). Regarding sexual behavior, 96.5% had reported their first sexual experience between 20 and 30 years, with 85.7% reporting one or two partners, and only 1.8% reported using condom. Multivariate logistic regression showed that circumcision, religion, marital status, age at first sex, number of sexual partners, education level, and misconception of knowledge are the main risk factors associated with HIV/AIDS. Conclusion. Our results showed that a number of diversity risk factors were associated with HIV/AIDS. It is unlikely that a holistic approach will be found to immediately change sexual-risk-relating behavior. Interventions including sustained educational programs, promotion of condom, and encouragement of voluntary testing and active involvement of the country's political and religious leaders will be needed to alleviate this problem. Sudan is bordered by countries with high rates of HIV infection. The first AIDS case was reported in 1986, and by 2011 the total number of cases reported had increased to 2218 . In 2002According to UNAIDS 2011, the most recent estimate of the prevalence of HIV/AIDS in Sudan after South Sudan separation indicated that HIV/AIDS prevalence is around 0.4% . AlthougThe spread of HIV is influenced by poverty and illiteracy, both of which are widespread in Sudan. The movement of people displaced by harsh environmental conditions has contributed to an increase in the number of HIV/AIDS cases. Refugees from other conflicts in the region also flee to Sudan. The war in Darfur resulted in the movement of large population fleeing from the war. This resulted in displacement of about 2.5 million people with many contracted the disease . The newSudan is a generally conservative and highly religious society where sexuality is not openly discussed, and a disease such as HIV/AIDS is surrounded by myths and taboos and even ignored in official circles. It is difficult and requires sensitivity to get people to talk openly about the disease. A review of the literature found no previous studies addressing HIV risk factors in Sudan. The main objective of this paper is to assess participants' knowledge about HIV/AIDS and to examine the main factors associated with HIV/AIDS in Sudan.This is observational cross-sectional study conducted using socio-demographic data collected from the records of Omdurman National Voluntary Counseling and Testing (VCT) Centre. According to the WHO (2005) , the VCTThe data used in the analysis cover the period from January 2010 to July 2010. A sample size with the marginal error 2.5% expected prevalence of 1.6% and confidence interval of 95%; nonresponse rate of 10% was calculated for 1016 participants. All the pieces of information have to be collected before the result of the test is obtained. Among the subjects selected, 870 agreed to participate in the study. Cultural inhibitions are behind people's reluctance to indulge in a direct and a free conversation about sex-related questions which are culturally dubbed taboos, especially among females. Thus, information related to sexual behavior was obtained through the “land telephone” or “mobile phone,” as almost all Sudanese have “mobile phones.” After the results were released, we found the sample covered both those with the infection detected (300) and without the infection detected (600) during this period. Many people who come for testing prefer not to return and discover the outcome of the test. SPSS version 17.0. Descriptive statistics  were used to describe the study variables. The chi-squared test was used to test for associations. The stepwise multiple logistic regression was used to assess the strength of the association of each variable adjusted for other confounders. All the regressor variables were treated as categorical. A P value <0.05 was considered statistically significant.The data were analyzed using Ethical clearance and permission was obtained from the local authorities of health department at the beginning of the data collection. The study proposal and instrument were approved by King Saud University's review board. Authorization was granted from the Center. During data collection, patients were informed that the information collected would be kept anonymous and that participation was completely voluntary.Data were obtained from 870 subjects, giving response rate of 85.6%. In a very conservative Muslim community like Sudan, people with AIDS are seen as ignominious. Stigma towards people with HIV is prevalent due to ignorance, lack of awareness, and misconception about transmission of the disease , and mosAge at first sexual intercourse, when it is before marriage, is associated with longer exposure to sexual activity and higher likelihood of accumulating sexual partners . IndividThe majority (98%) in our sample resist using the condom. This resistance is due to the lack of sufficient public health education; the use of condom has been viewed as a method of contraception more than a method to prevent sexually transmitted diseases and HIV/AIDS. Added to that is the problem of getting condoms. Condoms are only available in some pharmacies and are very costly, and even in those pharmacies are kept under the counter and only dispensed to those who ask for them.Our results about AIDS knowledge revealed that while all respondents had heard of AIDS, more than 60% did not believe that a healthy-looking person can carry the AIDS virus. This belief can lead to exposure to HIV infection since people can unlikely take precautions when having sexual intercourse with healthy-looking partners. We found more than 75% believe that mosquitoes transmit the HIV virus; those people may see the use of condom as futile. The belief that AIDS is a disease for “high-risk” group can influence people's perception and behavior. As a result, some people take their own risk because they did not identify these high-risk groups. Some see AIDS as punishment of immoral behavior so that those who see their lifestyle as being morally upright may see their chance of being infected by HIV is very low. Myth about cure of AIDS has been found in different Sudanese populations. About 48% believe that AIDS can be cured. Such misconception may encourage some persons to practice risky behavior by creating a false impression on them that they will be cured if they become infected with HIV. HIV transmission risk is not simple to be characterized or contained. There are multitudes of demographic, social, and biological factors that contribute to such risk. The findings of this study showed that circumcision, religion, marital status, age at first sex, education level, number of sexual partners, and misconception of HIV knowledge are significant predictors for HIV infections. These findings should be considered in any intervention strategy in the country.The most prevalent type of circumcision among females involves tight suturing of the cut edges of the labia majora, leaving only a very small opening, just large enough for passage of urine and menstrual blood. The prevalence of circumcision declined from 89.2% in 2000 to 69.4% in 2006; it is surprising that 65% reported being circumcised in our study . VaginalVarious studies in Africa have shown that male partners' sexual behavior is a major determinant of HIV infection among women not engaging in high-risk sexual practices  ProstituBehavioral data for our study was conducted using self-administered questionnaire, so denial of use is expected from some participants. Therefore, the results of our study should be interpreted with caution. Also, the study was based on a cross-sectional study design, which is not enough for generating strong associations between risk factors and HIV/AIDS.Our results provided new information regarding potential risk factors for contracting HIV. However, since this is the first study in Sudan, we included too many factors. We hope that future research addresses those factors separately and in depth. The prevention and control of HIV infections to be successful needs clear strategies to prevent new cases of the disease and offer proper treatment to all those currently infected persons. Voluntary HIV testing programs can be very useful in this regard as they can effectively reduce risk behaviors among those at higher risk.


As HIV/AIDS continues to pose a public health challenge Africa, the pandemic cuts across borders. It affects all the age groups including the geriatrics, despite engagement in risky sexual activities which increases HIV/AIDS infection. However, limited attention is paid to this population in mitigating the pandemic. This study therefore examined condom-use and perceived HIV/AIDS infection among geriatrics in Nigeria.The study was cross-sectional in design. A multi-stage sampling procedure was used to select 400-geriatrics. Pre-tested questionnaire developed, using information obtained from 10 Focus Group Discussion (FGD), was used to collect information. FGD data were analyzed thematically, while questionnaire data were analyzed using descriptive and statistically.Twenty-five percent of the participants had extra-marital sex since they attained elderly age. However, among this subgroup that had extra-marital sex, few (6.8%) used a condom. More males (5.3%) than females (1.5%) used condom during the last extramarital sex. Low level of condom-use was attributed to condom not worthwhile (34.5%) and opinion (50.0%) condom not made for the elderly. Moreover, FGD participants viewed sex could not lead to pregnancy and majority (60.3%) posited patronizing traditional healers and few (10.3%) use of herbs/concussion could prevent HIV/AIDS. Similarly, non-condom use was due to confidence in traditional herbs, perceived to protect against STIs including HIV/AIDS.Engagement in risky activities among elderly is a growing HIV/AIDS challenge. Condom-use is misconstrued probably due to knowledge gap. Without urgent measures to enable them protect themselves, development efforts will be in jeopardy. Investing in geriatric SRH is cost-effective intervention in mitigating HIV/AIDS pandemic.None declared.