A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. Impact of administrative restrictions on antibiotic use and expenditure in Ontario: time series analysis. Fluoroquinolone use and methicillin-resistant Staphylococcus aureus isolation rates in hospitalized patients: a quasi experimental study. Evaluation of an intervention designed to decrease the rate of nosocomial methicillin-resistant Staphylococcus aureus infection by encouraging decreased fluoroquinolone use. Comparison of ciprofloxacin, ofloxacin and pefloxacin for the prevention of the bacterial infection in neutropenic patients with haematological malignancies. Short course of ofloxacin for treatment of multidrug-resistant typhoid. Impact of a limited fluoroquinolone reimbursement policy on antimicrobial prescription claims. Single-dose fluoroquinolone therapy of acute uncomplicated urinary tract infection in women: results from a randomized, double-blind, multicenter trial comparing single-dose to 3-day fluoroquinolone regimens. Randomized controlled comparison of ofloxacin, azithromycin, and an ofloxacin-azithromycin combination for treatment of multidrug-resistant and nalidixic acid-resistant typhoid fever. Short courses of ofloxacin for the treatment of enteric fever. A randomized prospective comparison of oral versus intraperitoneal ciprofloxacin as the primary treatment of peritonitis complicating continuous ambulatory peritoneal dialysis. A randomized trial of roxithromycin in patients with acute leukemia and bone marrow transplant recipients receiving fluoroquinolone prophylaxis. Implementation of guidelines for sequential therapy with fluoroquinolones in a Belgian hospital. Fluoroquinolone prophylaxis for bacterial infections in neutropenic patients with hematologic malignancies. A randomized prospective comparison of oral levofloxacin plus intraperitoneal (IP) vancomycin and IP netromycin plus IP vancomycin as primary treatment of peritonitis complicating CAPD. Emergence of ciprofloxacin resistance in nosocomial methicillin-resistant Staphylococcus aureus isolates. Resistance during ciprofloxacin plus rifampin therapy for methicillin-resistant S aureus colonization. Ciprofloxacin, lomefloxacin, or levofloxacin as treatment for chronic osteomyelitis. [Prophylaxis with fluoroquinolones in patients with neutropenia]. Reduction of fever and streptococcal bacteremia in granulocytopenic patients with cancer. A trial of oral penicillin V or placebo combined with pefloxacin. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.
Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing.
                We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam.
                An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi).
                We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant.
                Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam.
                Controlled-Trials.com ISRCTN67946944. In a potential attempt to guide antibiotic prescribing based on current clinical evidence and mitigate the spread of antibiotic resistance, in March 2001 the Ontario Drug Benefit programme restricted reimbursement of two fluoroquinolone antibiotics--ciprofloxacin and ofloxacin--to its beneficiaries. Our objective was to determine the impact of this policy on the volume and cost of antibiotic prescribing.
                Weekly administrative data on antibiotic prescribing volumes and expenditures were analysed between January 1999 and September 2002 to estimate the effect of the policy changes using time series analysis.
                The policy changes were associated with a statistically significant shift downwards for the fluoroquinolones as a category (1905 fewer prescriptions each week, representing a saving of Can$105,707 a week), driven by a decrease in prescriptions for ciprofloxacin (2084 fewer prescriptions a week, saving Can$129,421 a week). Nitrofurantoin (200 more prescriptions a week, costing an extra Can$2082 a week) and trimethoprim-sulphamethoxazole (532 more prescriptions a week, costing an extra Can$1473 a week) demonstrated a statistically significant shift upwards. The latter also showed a decrease in trend and nitrofurantoin an increase in trend during the time period. There was no statistically significant change in either the total number of antibiotic prescriptions or expenditures associated with the policy of limiting their use.
                Although no direct cause and effect can be shown with these observational data, the results suggest that the change in reimbursement policy to restrict prescribing of fluoroquinolones decreased their use and associated expenditures. These decreases were offset by increases in the use of other antibiotics. The balance of consequent benefit and harm of these shifts in prescribing patterns needs to be examined carefully. Alternative solutions to encourage appropriate use of antibiotics deserve exploration. We investigated the possible association between fluoroquinolone use and the rate of methicillin-resistant Staphylococcus aureus (MRSA) recovery from consecutive hospitalized patients.
                We conducted a nonrandomized, prospective, controlled interventional "fluoroquinolone-free" study at 4 large teaching hospitals in northwest France, catering to a total of 5,882,600 persons. During the intervention period (January through December 2001), fluoroquinolone use was prohibited at 1 of the 4 hospitals (Caen Hospital), unless no effective alternative was available. Three university hospitals were used as controls because they had similar preintervention rates of MRSA.
                During the intervention period (2001), the annual rate of fluoroquinolone use decreased from 54 to 5 defined daily doses per 1000 patients per day at Caen Hospital and remained stable in the control hospitals. At the end of the intervention, the rate of MRSA isolation was significantly lower at Caen Hospital than at the control hospitals (353 [32.3%] of 1093 S. aureus isolates were MRSA, compared with 2495 [36.8%] of 6787 isolates; odds ratio, 0.82; 95% confidence interval, 0.69-0.99; P=.036), as determined on the basis of a marginal model that took into account within-hospital clustering. In a before-after time series analysis, compared with forecasted rates, there was a significant downward trend in observed monthly rates of MRSA isolation at Caen Hospital at the end of the intervention.
                This quasi experimental study confirms the association between fluoroquinolone use and MRSA isolation among hospitalized patients. Society for Health Care Epidemiology guidelines recommend decreasing the use of fluoroquinolone antibiotics in institutions where methicillin-resistant Staphylococcus aureus (MRSA) is endemic. We evaluated whether an intervention to limit fluoroquinolone use was associated with a lower rate of nosocomial MRSA infection and summarized changes in antibiotic use, changes in other variables potentially correlated with a lower rate of MRSA infection, and rates of nosocomial infections due to other pathogens.
                Single-center quasi-experimental design. A time series of nosocomial MRSA infections was measured at monthly intervals from July 2001 through June of 2004; there were 80 MRSA infections recorded. Segmented regression analysis (ie, quasi-Poisson generalized linear models) was used to evaluate variables possibly associated with the nosocomial MRSA infection rate.
                An 87-bed Veterans Affairs teaching hospital with an extended-care facility.
                A physician-directed computer-generated intervention designed to limit the use of fluoroquinolone antibiotics was initiated, and institutional changes in antibiotic use and nosocomial MRSA infection rates were tracked.
                After the intervention, fluoroquinolone use decreased by approximately 34%, and levofloxacin use decreased by approximately 50%. Decreased fluoroquinolone use was offset by increased cephalosporin, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole use. The nosocomial MRSA infection rate decreased from 1.37 to 0.63 episodes per 1,000 patient-days after the study intervention (P=.02). Coagulase-negative Staphylococcus and Enterococcus infection rates also decreased. However, the rate of infection with gram-negative organisms increased. The rate of MRSA infection was positively correlated with levofloxacin use (P=.01) and azithromycin use (P=.08), whereas it was negatively correlated with summer season (P=.05). In a subsequent model, the rate of MRSA infection was negatively correlated with the study intervention (P=.04).
                Reduction in the institutional use of fluoroquinolones may be associated with a lower nosocomial MRSA infection rate. The efficacy of oral prophylaxis with ciprofloxacin, ofloxacin or pefloxacin was assessed in preventing bacterial infection in neutropenic patients with treatment being allocated randomly before beginning chemotherapy. Bacteraemia developed in six of 78 episodes (8%) treated with ciprofloxacin, in eight of 80 (10%) allocated to ofloxacin and in 12 of 77 (16%) when pefloxacin was given. However, there were no episodes involving Gram-negative bacilli among those given ciprofloxacin whereas three and seven episodes occurred in patients given ofloxacin or pefloxacin respectively (P = 0.013). With the exception of Pseudomonas aeruginosa, all potential pathogens isolated were resistant to all three fluoroquinolones. Faecal anaerobes were not affected by treatment with pefloxacin whereas their total numbers were reduced in 12 cases who had received ofloxacin and in nine cases who had been given ciprofloxacin (P = 0.002). Fourteen patients (18%) were colonized with pefloxacin resistant P. aeruginosa at the end of treatment with this agent compared with only two and five of those given ciprofloxacin or ofloxacin respectively. A similar trend was seen with other resistant Gram-negative bacilli colonizing 14%, 20% and 23% of patients for ciprofloxacin, ofloxacin and pefloxacin, respectively. Ciprofloxacin was therefore superior to the other two fluoroquinolones in preventing infections due to Gram-negative bacteria in this population of neutropenic patients. In recent years, multiresistant strains of Salmonella typhi have emerged in many tropical countries. These strains remain highly sensitive to the fluoroquinolone antibiotics, although use of these drugs by children is considered contraindicated because of their reported toxicity in the cartilage of experimental animals. In a paired, open, randomized study during an epidemic of multidrug-resistant typhoid in southern Vietnam, two short-course ofloxacin regimens (15 mg/kg daily for 3 days and 10 mg/kg daily for 5 days) were compared for the treatment of uncomplicated typhoid fever. Of 438 patients enrolled (of whom 286 were < or = 14 years old), 228 had blood cultures positive for Salmonella species (S. typhi, 207; S. paratyphi A, 19; and S. choleraesuis, 2). There was one treatment failure in a patient who took only one dose of ofloxacin. Otherwise, both regimens were completely effective; there were no proven carriers, and there was no evidence of toxicity, particularly in children. A 3-day course of ofloxacin proved to be safe and highly effective in the treatment of uncomplicated, multidrug-resistant typhoid fever. To examine the influence on administrative pharmacy claims of a policy that limited the reimbursement of the fluoroquinolones and other antimicrobials in the senior population within Nova Scotia, Canada.
                The administrative claims database of the Nova Scotia Seniors' Pharmacare Program was used to identify all prescription claims for orally administered antibiotics and urinary antiinfectives. The number of beneficiaries receiving antimicrobials and the number, duration, and cost of prescriptions for antimicrobials were measured monthly. Descriptive time-series plots were used to compare antimicrobial use for two 12-month periods before the institution of the policy (December 1, 1994-November 30, 1995, and December 1, 1995-November 30, 1996) and the 12 months after the policy took effect (January 1, 1997-December 31, 1997).
                Following the implementation of the fluoroquinolone reimbursement policy, the number of patients using antimicrobials decreased by 2.2% and the number of prescriptions for antimicrobials decreased by 3.4%. Fluoroquinolone prescriptions decreased by 80.2%; prescriptions for sulfonamides and trimethoprim increased by 34.9%, cephalosporins by 17.0%, and macrolides and lincosamides by 16.5%. The only prescription duration to change was the fluoroquinolones, which increased by 25%. The average cost per antimicrobial user/year decreased from $35.24 during prepolicy period 2 to $27.51 during the postpolicy period.
                Prescription claims for fluoroquinolones in seniors decreased following the introduction of the policy. Total antimicrobial use also decreased, although this may be related to other factors. The effect of this policy change on patient outcomes requires further study. To compare the efficacy and safety of single-dose and 3-day fluoroquinolone treatment of uncomplicated urinary tract infection (UTI).
                Adult women with acute uncomplicated UTI were randomized to receive either a single dose of gatifloxacin (400 mg), 3 days of gatifloxacin (200 mg daily), or 3 days of ciprofloxacin (100 mg twice daily). Patients were assessed at four points during the study: before treatment (within 48 hours before the initiation of the study medication), at the end of treatment (by telephone contact on day 3), and twice after treatment completion (5 to 9 days after treatment [test-of-cure visit] and 29 to 42 days after treatment [only patients with a bacteriologic response of eradication at the test-of-cure visit]).
                The bacterial eradication rate for the single-dose gatifloxacin, 3-day gatifloxacin, and 3-day ciprofloxacin groups was 90%, 95%, and 89%, respectively; the clinical efficacy rate was 93%, 95%, and 93%, respectively, for microbiologically assessable patients at the test-of-cure visit. Eradication of the most common uropathogens, including Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, was achieved with gatifloxacin and ciprofloxacin. Single-dose gatifloxacin was equivalent to 3-day ciprofloxacin in both microbiologic and clinical efficacy.
                Single-dose and 3-day gatifloxacin were microbiologically and clinically equivalent to 3-day ciprofloxacin for the treatment of acute UTI among women. Single-dose gatifloxacin may offer advantages over 3-day fluoroquinolone therapy for uncomplicated UTI by decreasing secondary use of medical resources and improving patient compliance. Isolates of Salmonella enterica serovar Typhi that are multidrug resistant (MDR, resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) and have reduced susceptibility to fluoroquinolones (nalidixic acid resistant, Na(r)) are common in Asia. The optimum treatment for infections caused by such isolates is not established. This study compared different antimicrobial regimens for the treatment of MDR/Na(r) typhoid fever. Vietnamese children and adults with uncomplicated typhoid fever were entered into an open randomized controlled trial. Ofloxacin (20 mg/kg of body weight/day for 7 days), azithromycin (10 mg/kg/day for 7 days), and ofloxacin (15 mg/kg/day for 7 days) combined with azithromycin (10 mg/kg/day for the first 3 days) were compared. Of the 241 enrolled patients, 187 were eligible for analysis (186 S. enterica serovar Typhi, 1 Salmonella enterica serovar Paratyphi A). Eighty-seven percent (163/187) of the patients were children; of the S. enterica serovar Typhi isolates, 88% (165/187) were MDR and 93% (173/187) were Na(r). The clinical cure rate was 64% (40/63) with ofloxacin, 76% (47/62) with ofloxacin-azithromycin, and 82% (51/62) with azithromycin (P = 0.053). The mean (95% confidence interval [CI]) fever clearance time for patients treated with azithromycin (5.8 days [5.1 to 6.5 days]) was shorter than that for patients treated with ofloxacin-azithromycin (7.1 days [6.2 to 8.1 days]) and ofloxacin (8.2 days [7.2 to 9.2 days]) (P < 0.001). Positive fecal carriage immediately posttreatment was detected in 19.4% (12/62) of patients treated with ofloxacin, 6.5% (4/62) of those treated with the combination, and 1.6% (1/62) of those treated with azithromycin (P = 0.006). Both antibiotics were well tolerated. Uncomplicated typhoid fever due to isolates of MDR S. enterica serovar Typhi with reduced susceptibility to fluoroquinolones (Na(r)) can be successfully treated with a 7-day course of azithromycin. Typhoid fever continues to be a major public health problem in tropical countries, exacerbated in recent years by the spread of multi-drug resistant strains of Salmonella typhi. Short treatment courses of fluoroquinolones are effective, and have the advantage of reduced cost and increased compliance, but the optimal length of treatment is unknown. In an open, randomized comparison, 107 adults with uncomplicated enteric fever (95 of whom had positive blood cultures for S. typhi and 5 for S. paratyphi) were treated with oral ofloxacin, 15 mg/kg/d for 2 d or 10 mg/kg/d for 3 d. Mean fever clearance times were the same in the 2 treatment groups (97 h). There were 7 treatment failures, one in the 2 d group and 6 in the 3 d group (P = 0.07). Three of the 5 patients infected with nalidixic acid resistant strains of S. typhi had treatment failures, compared with 4 of 90 with nalidixic acid sensitive isolates (P < 0.0001; relative risk 13.5, 95% confidence interval 4.1-43%). Treatment with ofloxacin for 2 or 3 d is equally effective in adults with uncomplicated enteric fever caused by nalidixic acid sensitive strains of S. typhi. The epidemiology and management of nalidixic acid resistent typhoid needs further investigation. The present study compared oral versus intraperitoneal (ip) ciprofloxacin (ciproxin) as primary treatment of bacterial peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD) in a randomized, prospective trial. A total of 54 episodes in 46 patients were recruited for study. After excluding nonbacterial episodes and those not treated according to protocol, 48 episodes evenly divided between the two treatment arms were eligible for analysis. The primary cure rate was 41.7% and 66.7%, respectively, in the oral and ip treatment group. Half of those who failed or relapsed were due to infection with resistant, mostly gram-positive bacteria, which accounted for 79% of culture-positive episodes. Of the gram-positive isolates 42.3% were either resistant or intermediately susceptible to ciproxin compared to 16.7% of gram-negative isolates. The high level of bacterial resistance to ciproxin and treatment failure rate were related to the previous exposure to fluoroquinolones. Inadequate trough peritoneal drug levels also accounted for the failures in the ip but not the oral treatment group. We conclude that oral ciproxin is ineffective as a primary treatment of CAPD peritonitis in patients previously exposed to fluoroquinolones and that when administered ip, a dose of 50 mg/L instead of 25 mg/L of ciproxin should be used as maintenance in order to achieve adequate trough peritoneal drug levels. Fluoroquinolone prophylaxis in patients with profound neutropenia may be useful for preventing gram-negative bacterial infection, but it is ineffective against gram-positive bacterial infections in the bloodstream, particularly those caused by streptococci and coagulase-negative staphylococci, which appear to have emerged as significant causes of morbidity, decreased treatment efficacy, and the increased costs of empiric antimicrobial therapy. In a prospective, randomized, open trial, we evaluated the efficacy and safety of oral roxithromycin (150 mg twice daily) as additional antibacterial prophylaxis in 131 adult patients with acute leukemia and bone marrow transplant recipients receiving oral ofloxacin. In comparison with patients given ofloxacin alone, fewer patients receiving ofloxacin plus roxithromycin developed bacteremia caused by viridans group streptococci (incidence, 9 versus 0%; P = 0.03), while the incidence of bacteremia caused by other organisms, the incidence of febrile episodes from any cause, the risk of infection-associated complications (including prolonged or secondary fever, pneumonia, septic shock, need for mechanical ventilation, and/or infection-related death), and antimicrobial usage for therapy were comparable between both groups. Adverse events possibly related to the study drugs were slightly more common among the patients receiving the combination treatment (P = 0.05). Although effective for the prevention of streptococcal bacteremia, the addition of roxithromycin to a fluoroquinolone should not be used routinely as a prophylactic regimen in patients with profound neutropenia, but it might be considered and may be useful for cancer patients with a particularly high risk of streptococcal infection and related complications. This study measured the impact of three interventions for physicians, in order to implement guidelines for sequential therapy (intravenous to oral conversion) with fluoroquinolones.
                A Belgian university hospital with 1,065 beds. Method The first intervention consisted of the hospital-wide publication of guidelines in the local drug letter towards all prescribers. The consumption of fluoroquinolones was measured by means of an interrupted time-series (ITS) analysis 21 months before (period A) and 24 months after publication (period B). The second intervention was an educational interactive session, by infectious disease specialists, to the medical staff of orthopaedics and endocrinology. The third intervention comprised a proactive conversion programme on the abdominal surgery, gastro-enterology and plastic surgery wards, where pharmacists attached a pre-printed note with a suggestion to switch to an oral treatment every time a patient met the criteria for switching. The second and third intervention took place 6 months after the first intervention. Fluoroquinolone treatments were evaluated during a 2 month period before (group 1) and after the introduction of the second (group 2) and third (group 3) intervention.
                The monthly ratio of intravenous versus total fluoroquinolone consumption (daily defined doses per 1,000 bed days) was measured to assess the impact of the first intervention. The impact of the second and third intervention was measured in relation to the number of days that intravenous therapy continued beyond the day that the patient fulfilled the criteria for sequential therapy and the antibiotic cost.
                The ITS demonstrated a reduction of 3.3% in the ratio of intravenous versus total consumption after the publication of the guidelines (P = 0.011). In group 1, patients were treated intravenously for 4.1 days longer than necessary. This parameter decreased in group 2 to 3.5 days and in group 3 to 1.0 day (P = 0.006). The mean additional cost for longer intravenous treatment decreased from 188.0 euro in group 1, to 103.0 euro in group 2 and 44.0 euro in group 3 (P = 0.037).
                This study demonstrated that active implementation of guidelines is necessary. A proactive conversion programme by a pharmacist resulted in a reduction in the duration of the intravenous treatment, and the treatment cost. The use of fluoroquinolones as prophylaxis for bacterial infections in patients with chemotherapy induced neutropenia is debatable. The present study was conducted to assess the prophylactic efficacy of fluoroquinolones in adult neutropenic patients with hematologic malignancies.
                For the period 1994 through 2000 a prospective, randomized trial was conducted at the University Clinic of Hematology (Medical University, Plovdiv). Two groups of patients were included--experimental group, consisting of 36 patients with 41 granulocytopenic episodes and a control group of 34 patients with 41 granulocytopenic episodes. Non parametrical and psi methods were used for statistical analysis. Kaplan-Meier test was employed to determine patients' survival rate. Comparison of survival rates between the two groups was performed using the log-rank test.
                A statistically significant difference between the two groups was found in the number of infection-free neutropenic episodes (P < 0.001), in infection-related mortality rate (p = 0.001) and mortality rate within 1 month of the onset of infection (p < 0.001). Difference in long term survival rates was not statistically significant (p > 0.05).
                Prophylaxis with fluoroquinolones reduced the occurrence of infection in adult neutropenic patients without affecting the long-term survival. Moreover, it is especially beneficial for patients with severe neutropenia and during the active phase of the disease. To compare the therapeutic efficacy of daily oral levofloxacin plus intermittent intraperitoneal (IP) vancomycin (group 1) versus daily IP netromycin and intermittent IP vancomycin (group 2) in the primary treatment of peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD).
                A randomized multicenter prospective open-label comparative clinical study.
                University and Hospital Authority hospitals in Hong Kong.
                All CAPD patients who developed bacterial or culture-negative peritonitis beyond 28 days of a previous episode and without evidence of septicemia, associated tunnel infection, or known sensitivity to trial medications were accepted into the clinical trial.
                A total of 101 patients entered the trial. The primary cure rate was 74.5% for group 1 and 73.6% for group 2. Baseline culture results appeared to influence the clinical outcome: the primary cure rate for culture-negative, gram-positive, and gram-negative episodes was 83.3%, 78.6%, and 42.9% for group 1 and 69.1%, 76.9%, and 71.3% for group 2, respectively. The primary cure rate also varied considerably among individual centers and was particularly noticeable in group 1. In the latter group, it correlated closely with in vitro levofloxacin resistance which in turn correlated closely with previous exposure to fluoroquinolones.
                Oral levofloxacin in combination with intermittent IP vancomycin has comparable efficacy to IP netromycin combined with intermittent IP vancomycin as primary treatment in CAPD peritonitis, but is simpler and more cost-effective to administer. It may be recommended as primary therapy in centers with relatively low exposure and, therefore, low background resistance to fluoroquinolones. We initiated a randomized, single-blinded trial of ciprofloxacin plus rifampin vs sulfamethoxazole and trimethoprim plus rifampin in the therapy for patients who underwent colonization with methicillin-resistant Staphylococcus aureus (MRSA). Patients who were colonized with MRSA received 2 weeks of either regimen. The study was terminated after the enrollment of 21 subjects due to the recognition of ciprofloxacin resistance in 10 of 21 new MRSA isolates during the last 2 months of the study. Five of the 10 patients with ciprofloxacin-resistant MRSA isolates had never received ciprofloxacin. Long-term (6-month) eradication had been achieved in only three of 11 ciprofloxacin plus rifampin and four of 10 sulfamethoxazole and trimethoprim plus rifampin recipients. The use of this new fluoroquinolone for the eradication of MRSA colonization is usually not effective and may risk the development of ciprofloxacin resistance in MRSA within the hospital environment. The efficacy and safety of three oral fluoroquinolones (lomefloxacin, levofloxacin, and ciprofloxacin) for the treatment of chronic osteomyelitis were analyzed. Twenty-seven patients had documented infections with quinolone-sensitive organisms and received either lomefloxacin, levofloxacin, or ciprofloxacin. Levofloxacin was effective therapy for 9 of 15 (60%) patients. Lomefloxacin was effective therapy for five of seven (71%) patients, and ciprofloxacin was effective therapy for two of five patients (40%). Average follow-up was 11.8 months for patients who completed the course of therapy, and the average duration of therapy was 60.6 days. Gram-positive bacteria were isolated from 18 patients, and 11 patients were cured. Oral fluoroquinolones can be safe, effective therapy if they are given for a prolonged course as treatment for infections caused by susceptible gram-positive as well as gram-negative organisms and in combination with adequate surgical debridement. In order to evaluate whether the prophylactic use of fluoroquinolones diminishes the incidence of infections and/or mortality during neutropenia, we undertook a prospective, aleatory and controlled study in non-hospitalized adult patients with acute leukemia and chemotherapy-induced neutropenia including twenty five episodes of neutropenia including twenty five episodes of neutropenia which had occurred in 14 patients who were randomly selected either to receive or not quinolones (norfloxacin 800 mg daily or ciprofloxacin 1000 mg daily). Both groups were similar in terms of sex, age, underlying disease, chemotherapy for hematologic malignancy, duration and severity of neutropenia. The use of quinolones was associated with a delay in the fever onset during neutropenia (p = 0.0448), a decrease in the proportion of neutropenic febrile days (p = 0.0456), a decrease of infections caused by gram-negative bacilli (p = 0.037) and an increase of Streptococcus infections (p = 0.0857). There was no significant decrease in mortality, incidence of severe infections, proportion of neutropenic episodes without fever, empiric use of amphotericin B or fungal infections between both groups. The results of this study demonstrate that the prophylactic use of fluoroquinolones does not diminish the infectious morbidity and/or mortality in these patients. To determine the effect of oral penicillin V combined with a fluoroquinolone (pefloxacin) on the occurrence of fever and streptococcal and other gram-positive coccal bacteremic infections in granulocytopenic patients with cancer.
                Prospective randomized double-blinded placebo-controlled prophylactic trial.
                Inpatient setting in multiple cooperating cancer centers.
                Convenience sample with a total of 551 granulocytopenic patients, 95% of whom had leukemia or underwent bone marrow transplantation.
                Penicillin V (500 mg twice a day) vs placebo given in combination with oral pefloxacin (400 mg twice a day).
                Occurrence of fever and/or infection.
                Fever or infection (without fever) developed in 190 (71%) of 268 evaluable patients in the penicillin arm compared with 213 (80%) of 268 evaluable patients in the placebo arm (P = .03; 95% confidence interval [CI] for the difference, -16% to -1%). Bacteremia occurred in 58 (22%) of 268 placebo-treated patients and in 38 (14%) of 268 penicillin-treated patients (P = .03; 95% CI for the difference, -14% to -1%), primarily due to a reduction in streptococcal bacteremic episodes that occurred in 14 penicillin-treated patients (5%) and in 27 placebo-treated patients (10%) (P = .05; 95% CI for the difference, -9% to -0.3%). Gram-negative rod bacteremias occurred in only two patients (1%) and in five patients (2%), respectively. Logistic regression analysis also supported the treatment effect on the development of bacteremia.
                These results demonstrate that the addition of penicillin V to fluoroquinolone prophylaxis in granulocytopenic patients with cancer effectively reduces febrile episodes and the incidence of bacteremia, especially that due to streptococcal species.
Generally, fluoroquinolones performed well in treating typhoid, and maybe superior to alternatives in some settings. However, we were unable to draw firm general conclusions on comparative contemporary effectiveness given that resistance changes over time, and many studies were small. Policy makers and clinicians need to consider local resistance patterns in choosing a fluoroquinolone or alternative.
There is some evidence that the newest fluoroquinolone, gatifloxacin, remains effective in some regions where resistance to older fluoroquinolones has developed. However, the different fluoroquinolones have not been compared directly in trials in these settings.