The most frequent cause of catheter infection is a bacterium that colonizes the skin. The Gram stain tells us that it is a staphylococcus, most of the species of this genus acquired in-hospital are methicillin resistant, so they are considered resistant to Cloxacillin, Cefazolin and there are no clinical data about the efficacy of linezolid for the treatment of systemic infection related to catheter. This, plus the experience with vancomycin use in this setting is considered the empirical choice for vancomycin.

The most frequent cause of catheter infection is a bacterium that colonizes the skin. The Gram stain tells us that it is a staphylococcus, most of the species of this genus acquired in-hospital are methicillin resistant, so they are considered resistant to Cloxacillin, Cefazolin and there are no clinical data about the efficacy of linezolid for the treatment of systemic infection related to catheter. This, plus the experience with vancomycin use in this setting is considered [HIDDEN].

An 85-year-old man with a peripheral venous catheter who, one week after being hospitalized for a stroke, begins with shivering and fever. Blood cultures are performed and microbiology reports that gram-positive cocci are growing in clusters. Pending the antibiogram, what is the most appropriate antibiotic treatment?

[Study on sepsis in the elderly at Nagoyashi-Koseiin Geriatric Hospital].

A study based on clinical analysis was conducted regarding the 125 episodes in the elderly 112 patients of sepsis who were 70 (average 83.8 +/- 7.5) years old at Nagoyashi-Koseiin Geriatric Hospital from 1985 through 1994. 1) The backgrounds of the elderly patients with sepsis were as follows: bedridden (72.8%), urinary catheter in place (61.2%), central venous catheter in place (48.8%), and prior antibiotic use (40.8%). All patients had an underlying disease. 2) Organisms isolated were Escherichia coli (21.2%), Staphylococcus aureus (18.4%); Coagulase-negative staphylococci (CNS) (17.4%) and Candida albicans (6.1%). Chronologically, the quantity of gram-positive cocci increased while that of gram-negative bacilli decreased. As the age of the patients increased, the frequency of infections by Methicillin-resistant Staphylococcus aureus (MRSA), E. coli, and/or multiple bacteria increased, while that of infections by CNS and gram-negative bacilli excluding E. coli decreased. 3) The primary infected sites were the urinary tract system (24.8%), central venous catheter (21.6%) and unknown (31.2%). 4) The primary clinical observations were fever exceeding 38.0 degrees C (88.0%), tachycardia (60.8%), shivering (44.0%) and cyanosis (32.8%). 5) Complications were multiple organ failure (33.6%), septic shock (26.4%) and disseminated intravascular coagulation (22.4%). 6) The prognosis indicated that 65.6% were survivors, and 34.4% were nonsurvivors. At the onset of sepsis, weight, blood pressure, serum albumin, and total cholesterol in the nonsurvivors were significantly lower than those in the survivors, whereas heart rate, GOT, LDH, and BUN in the nonsurvivors were significantly higher than those in the survivors.

[Peripheral venous catheter-related E. faecalis sepsis with fatal outcome].

A 82 year-old man was admitted with a facial Herpes zoster reactivation and a zoster-related meningoencephalitis. He was treated with Aciclovir over a peripheral venous catheter that was placed in the right elbow pit. The meningoencephalitis subsided without neurological deficits, but the patient developed a catheter-associated phlebitis. An oral cephalosporin was prescribed and the patient discharged. After developing a fever and general discomfort he was readmitted to hospital three days later. A 3 × 3 cm abscess in the elbow pit was incised and drained, but no swab or blood cultures were taken. When the patient's condition got worse an echocardiogram was ordered. It showed vegetations on the aortic and mitral valves as well as on the cardiac pacemaker wires. Blood cultures were positive for Enterococcus faecalis. Although a therapy with vancomycin and ampicillin was started, the patient's condition impaired. Surgical valve replacement was initiated, but the patient expired 5 weeks later due to septic multi-organ failure. The danger of peripheral venous catheter infections is frequently underrated, early identification of the causing pathogen, sensitivity testing and proper antibiotic treatment are of tremendous importance. Clinical sings of sepsis must under no circumstances be overlooked.

[Elizabethkingia meningosepticum bacteremia in a patient with Bardet-Biedl syndrome and chronic renal failure].

Elizabethkingia meningosepticum, a gram-negative opportunistic pathogen may cause life-threatening nosocomial infections especially in newborns and immunosuppressive patients. This bacterium has a peculiar antibiotic resistance profile. It is resistant to most of the antibiotics against gram-negative bacteria and susceptible to antibiotics that are used to treat gram-positive bacteria, such as vancomycin and trimethoprim-sulphamethoxazole (SXT). For this reason appropriate treatment of E.meningosepticum infections are based on the proper identification of bacteria. In this report, a case of catheter-related E.meningosepticum bacteremia in a patient with chronic renal failure due to Bardet-Biedl syndrome, a genetic disorder characterized by multiorgan dysfunction, was presented. A 25-year-old male patient with Bardet-Biedl syndrome was admitted to the emergency room with the complaints of high fever with shivers that started the day before. The patient had a femoral dialysis catheter. Venous blood samples drawn at the time of administration were cultured immediately. Two days later, blood cultures which yielded positive signals were passaged onto blood and MacConkey agar plates and after incubation at 37°C for 16 hours, wet-raised colonies with clear margin, gray colour and large size similar to gram-negative bacterial colonies were detected on blood agar medium. No growth was observed on MacConkey agar plate at the end of five days. The isolate was found positive for KOH, oxidase, catalase, urease, esculine and MOI (Motility Indole Ornithine) tests, whereas it was citrate negative. Gram staining revealed faintly stained thin gram-negative bacilli. The isolate was identified as E.meningosepticum by Vitek® 2 system (bioMérieux, USA), and confirmed by sequence analysis of 16S RNA gene region amplified with PCR method. The antibiotic susceptibility profile of the strain was detected by the Vitek 2 system, while vancomycin susceptibility was investigated by Kirby-Bauer disc diffusion method. The isolate was found resistant to ampicillin/sulbactam, piperacillin/tazobactam, ceftazidime, cefepime, meropenem, imipenem, amikacin, gentamicin, netilmicin, levofloxacin, tetracycline, colistin and rifampicin; intermediate to tigecyclin and tetracyclin; susceptible to cefoperazone/sulbactam, ciprofloxacin, levofloxacin, SXT and vancomycin. One gram vancomycin once every four days was administered to the patient, however on the ninth day of the treatment he developed fever again. Blood cultures obtained again yielded E.meningosepticum. After changing his dialysis catheter and extending the vancomycin treatment to 15 days, the patient was discharged with cure. In conclusion, clinicians should consider E.meningosepticum as a possible causative agent of bacteremia non-responsive to the empirical antibiotic regimens and when gram-negative bacteria are isolated from the blood cultures of such patients with underlying diseases. Accurate and prompt identification of E.meningosepticum will allow immediate administration of the specific antibiotic treatment, thereby decreasing the mortality and morbidity rates.

[A case of vancomycin resistant Leuconostoc meningitis].

Although Leuconostoc species are rarely pathogenic for humans, they may sometimes give rise to serious infections. In this report, a case of meningitis caused by vancomycin resistant Leuconostoc spp. was reported. Fifty-seven years old female patient was admitted to the hospital with the complaints of headache and sudden onset of unconsciousness and hospitalized in the neurosurgery department because of subarachnoidal hemorrhage. Patient was followed up with dexamethasone treatment and daily lumbar puncture without any surgical intervention. The findings of hemorrhage were receded in the cerebrospinal fluid (CSF) and the consciousness of the patient improved gradually. However, on the ninth day of the hospitalization, the patient became febrile and confused; white blood cell count was 7920/mm3, protein level was 1952 mg/l in the CSF examination. Nosocomial meningitis was diagnosed and empirical treatment with ceftazidime (3 x 2 g/day) and vancomycin (4 x 500 mg/day) was started. CSF culture revealed growth of gram-positive cocci which were identified as Leuconostoc spp. by VITEK 2 Compact (Biomerieux, France) and Phoenix Instrument (Becton-Dickinson, USA) systems. Since the isolate was found susceptible to penicillin, ampicillin, cefotaxime, cefepime, chloramphenicol, clindamycin, erythromycin and linezolid, and resistant to vancomycin by disk diffusion and miniAPI ATB STREP 5 (Biomerieux, France) methods, the treatment was switched to linezolid (2 x 600 mg/day). Vancomycin and teicoplanin resistance was confirmed by E-test. The treatment was continued with linezolid and the patient's clinical condition improved after 14 days of treatment. The possible way of Leuconostoc transmission in this case was thought to be the lumbar punctures performed during the follow-up of subarachnoid hemorrhage. This presentation which demonstrated that Leuconostoc spp. might rarely lead to meningitis, also pointed out that when a vancomycin resistant gram-positive coccus was identified, Leuconostoc spp. should always be kept in mind.

Changes in 4-year antimicrobial resistance pattern of gram-positive bacteria at the main referral teaching hospital, Tehran, Iran.

Infectious diseases are one of the most common causes of morbidity and mortality and the spread of resistant microorganisms is playing a significant role in this regard. The purpose of this study was to assess the trend in antimicrobial resistance of gram-positive bacteria at the main referral teaching hospital in Tehran during a 4-year period. All patients' biological isolates such as blood, urine, wound drainage, synovial fluid, sputum, and cerebrospinal fluid sent to the central laboratory of the hospital from 2007 to 2010 for identification and subsequently, antimicrobial susceptibility testing by Kirby-Bauer disc diffusion method were considered. All isolates (100%) of S. aureus were sensitive to vancomycin and linezolid and resistant to amoxicillin. The rate of S. aureus resistance to oxacillin increased from 60.78% in 2007 to 72% in 2010. All isolates of Streptococci in 2007 and 2008 were sensitive to vancomycin; while, 3.33% and 4.76% of Streptococci isolates were reported to be vancomycin-resistant in 2009 and 2010, respectively. Enterococci isolated from the entire specimens were identified to be sensitive to teicoplanin and linezolid and resistant to cloxacillin and oxacillin. The rates of Enterococci sensitivity to vancomycin were 90.91%, 81.25%, 86.67%, and 93.3% in 2007, 2008, 2009, and 2010, respectively. Changes of antibiotics sensitivity against g positive pathogens were significant during four years in this study. To minimize the spread of resistant gram positive pathogens, periodic and regular surveillance of antimicrobial resistance pattern is highly recommended.

Diagnosis and management of Staphylococcus aureus bacteraemia.

Staphylococcus aureus bacteraemia (SAB) is common. Around 8000 cases occur per year in Australia, of which 60% are hospital- or healthcare-associated. Risk factors for SAB include injectable drug use, haemodialysis, indwelling vascular catheters and immunosuppression. Metastatic infection develops in up to one-third of patients with SAB, with joints and heart valves being the most commonly affected sites. Community-acquisition,persistent fever, positive blood cultures after 48 h of treatment and the presence of embolic lesions correlate with the presence of complicated SAB (i.e. high risk of endocarditis and/or other metastatic complications). All patients require careful clinical evaluation to exclude endocarditis and other metastatic foci. Echocardiography,preferably transoesophageal echocardiography, should be performed to exclude endocarditis. Most patients with SAB, and all with features of complicated SAB, require prolonged intravenous antibiotic therapy (at least 4 weeks), but a subgroup with good prognostic features may be suitable for shorter intravenous therapy (2 weeks). Penicillinase-resistant penicillins (e.g.flucloxacillin) are the agents of choice for SAB with methicillin-sensitive strains. Vancomycin or first-generation cephalosporins are alternatives but have lower antimicrobial activity than flucloxacillin. However, vancomycin remains the therapy of choice for SAB due to methicillin-resistant strains. Combination therapy with gentamicin may be useful for the first few days of treatment in selected patients, but otherwise there are few data to support the use of combination regimens in SAB. Newer agents such as linezolid and quinupristin/dalfopristin may have a role in selected patients, especially in SAB due to S. aureus strains with reduced susceptibility to vancomycin.

InternalMed_Harrison

if the organism does not exhibit high-level resistance to aminoglycosides (see Table 174–1, footnote c). eQuinupristin-dalfopristin (Q/D) and linezolid are listed in the American Heart Association’s recommendations for the treatment of endocarditis caused by vancomycinand ampicillin-resistant E. faecium. fAgents that may be useful in combination with Q/D (if the isolate is susceptible to each agent) include doxycycline with rifampin (one reported case) and fluoroquinolones (one reported case). gIn selected cases of catheter-associated bacteremia, removal of the catheter and a short course of therapy (~5–7 days) may be sufficient. A single positive blood culture that is likely to be associated with a catheter in a patient who is otherwise doing well may not require therapy after removal of the catheter. hFluoroquinolone antibiotics (e.g., moxifloxacin) and rifampin (if the isolate is susceptible to each agent) reach therapeutic levels in the cerebrospinal fluid (CSF). iIntrathecal Q/D

Linezolid

Linezolid was associated with significantly greater mortality than the comparator antibiotics. When data from all participants were pooled, the study found that 21.5% of those given linezolid died, compared to 16% of those not receiving it. The difference was found to be due to the inferiority of linezolid in the treatment of Gram-negative infections alone or mixed Gram-negative/Gram-positive infections. In participants whose infection was due to Gram-positive bacteria alone, linezolid was as safe and effective as vancomycin. In light of these results, the FDA issued an alert reminding healthcare professionals that linezolid is not approved for the treatment of catheter-related infections or infections caused by Gram-negative organisms, and that more appropriate therapy should be instituted whenever a Gram-negative infection is confirmed or suspected.

InternalMed_Harrison

Blood Cultures Isolation of the causative microorganism from blood cultures is critical for diagnosis and for planning treatment. In patients with suspected NVE, PVE, or CIED endocarditis who have not received antibiotics during the prior 2 weeks, three 2-bottle blood 820 culture sets, separated from one another by at least 2 h, should be obtained from different venipuncture sites over 24 h. If the cultures remain negative after 48–72 h, two or three additional blood culture sets should be obtained, and the laboratory should be consulted for advice regarding optimal culture techniques. Pending culture results, empirical antimicrobial therapy should be withheld initially from hemodynamically stable patients with suspected subacute endocarditis, especially those who have received antibiotics within the preceding 2 weeks. Thus, if necessary, additional blood culture sets can be obtained without the confounding effect of empirical treatment. Patients with acute endocarditis or with

[Use of antibiotics for the treatment of multiresistant gram positive cocci infections in critical patients].

This study has been designed to know the use of these antibiotics (ATB) in Intensive Care Units (ICUs). A multicentric, prospective, observational study was conducted. In cluded as cases were the indications of vancomycin (VAN), teicoplanin (TPN), quinupristin/dalfopristin (Q/D) and linezolid (LZD). A total of 826 indications (VAN 52.1%, TPN 36.6%, LZD 11.6% and Q/D 0%) were analyzed, 793 (96%) as treatment and 33 (4%) as prophylaxis in 818 patients. Serious sepsis or septic should occurred in 55.9% of the patients treated. The most common infections were pneumonia and catheter-related bacteremia, 48.3% of all the infections being acquired in ICUs. LZD was used mostly in mechanical-ventilation related pneumonia (p = 0.001), VAN in community Central Nervous System infections (p = 0.01) and in catheter-related bacteremia (p = 0.001), TPN in community pneumonia (p = 0.01) and in catheter-related bacteremia (p = 0.001). Treatments were empirical in 65.8% and diagnosis of gram positive cocci was confirmed in 48.3% of them. Staphylococcus aureus was isolated more in the LZD-treated group. Initial treatment was modified 224 times, this occurring more frequently in the VAN-treated group. The reason for this change was clinical failure 59 times, this being more frequent in the TPN group and less frequent in the patients treated with LZD, which was the drug used the most in rescue therapies (43/69, 62.3%). Adverse events, probably related to the ATB, were identified in 36/826 (4.4%) cases. The most common use of this ATB was to treat ICU-acquired infections. VAN was the most frequently used drug. Treatments with LZD were modified less frequently for clinical failure and this drug was the one most used in rescue therapies. This information indicates an appropriate use of these ATB in an important percentage of critically patients.

InternalMed_Harrison

Blood cultures should be repeated daily until sterile in patients with endocarditis due to S. aureus or difficult-to-treat organisms, rechecked if there is recrudescent fever, and performed again 4–6 weeks after therapy to document cure. Blood cultures become sterile within 2 days after the start of appropriate therapy when infection is caused by viridans streptococci, enterococci, or HACEK organisms. In S. aureus endocarditis, β-lactam therapy results in sterile cultures in 3–5 days, whereas in MRSA endocarditis, positive cultures may persist for 7–9 days with vancomycin or daptomycin treatment. MRSA bacteremia persisting despite an adequate dosage of vancomycin may indicate infection due to a strain with reduced vancomycin susceptibility and therefore may point to a need for alternative therapy. When fever persists for 7 days despite appropriate antibiotic therapy, patients should be evaluated for paravalvular abscess, extracardiac abscesses (spleen, kidney), or complications

Linezolid

Catheter-related infections In March 2007, the FDA reported the results of a randomized, open-label, phase III clinical trial comparing linezolid to vancomycin in the treatment of catheter-related bloodstream infections. Patients treated with vancomycin could be switched to oxacillin or dicloxacillin if the bacteria that caused their infection was found to be susceptible, and patients in both groups (linezolid and vancomycin) could receive specific treatment against Gram-negative bacteria if necessary. The study itself was published in January 2009.

Central venous catheter

Antibiotics are nearly always given as soon as a patient is suspected to have a catheter-related bloodstream infection. However, this must occur after blood cultures are drawn, otherwise the culprit organism may not be identified. The most common organisms causing these infections are coagulase negative staphylococci such as staphylococcus epidermidis. Infections resulting in bacteremia from Staphylococcus aureus require removal of the catheter and antibiotics. If the catheter is removed without giving antibiotics, 38% of people may still develop endocarditis. Evidence suggests that there may not be any benefit associated with giving antibiotics before a long-term central venous catherter is inserted in cancer patients and this practice may not prevent gram positive catheter-related infections. However, for people who require long-term central venous catheters who are at a higher risk of infection, for example, people with cancer who at are risk of neutropenia due to their

Treatment of mycobacterial exit-site infections in patients on continuous ambulatory peritoneal dialysis.

Exit-site infections (ESIs) are frequently due to gram-positive organisms and occasionally to gram-negative organisms. Initial empiric antibiotic therapy is therefore directed against these organisms until culture reports are available. Two cases of ESI associated with Mycobacterium are here reported. The first patient, a 63-year-old man with type 2 diabetes, recently treated for Staphylococcus epidermidis peritonitis, presented with acute purulent drainage at the catheter exit site, accompanied by pain and erythema. No tunnel abscess was identified by ultrasound. Empiric antibiotic therapy was initiated with ofloxacin and vancomycin. A rapid-growing acid-fast bacillus (AFB) noted four days after culture was eventually identified as Mycobacterium fortuitum. Ofloxacin was continued, vancomycin was discontinued, and clarithromycin was added. The ESI initially showed improvement; therapy was therefore continued for several months. However, cultures remained positive for M. fortuitum, and the catheter was removed 5 months after therapy was initiated. The second patient, a 28-year-old woman, presented with severe pain and tenderness at the exit site without erythema or drainage. Empiric therapy with cefazolin, gentamicin, and cephalexin was initiated. Gram-positive cocci and an AFB were identified from the exit-site culture, and antibiotics were initially changed to clarithromycin, trimethoprim/sulfamethoxazole, and ofloxacin. The organisms were subsequently identified as M. chelonae-M. abscessus complex and coagulase-negative Staphylococcus. The patient continued to improve after 3 weeks of antibiotic therapy. However, despite the initial improvement in the ESI, the M. chelonae-M. abscessus complex continued to grow, and amikacin was added intravenously. Despite continued treatment, the ESI did not resolve, and the catheter was removed after 4 months of therapy. Despite unusual exist-site infections with rapidly growing AFBs, both patients continued continuous ambulatory peritoneal dialysis (CAPD) while undergoing treatment for ESI. Catheters were left intact, as improvement was initially seen with no evidence of tunnel infection or peritonitis. Rapid-growing AFB should be considered another possible causative agent for ESI. Two cases of atypical mycobacterial exit-site infection are presented to illustrate the difficulties in managing this complication of peritoneal dialysis. Ofloxacin--or other quinolones--may provide a better spectrum of coverage when choosing empiric therapy in patients presenting with ESI.

[A case report of an infective endocarditis caused by methicillin-resistant Staphylococcus aureus with successful mitral valve replacement].

We report a case of successful mitral valve replacement performed on the patient who is an infective endocarditis due to MRSA. She was 27-year-old female and treated by antibiotics medication because of remittent fever two years ago. On August 1995, cerebral infarction occurred and she was pointed out endocarditis. After high fever continued, blood cultures demonstrated MRSA. Furthermore, echocardiography showed vegetation on posterior mitral valve leaflet and moderate mitral regurgitation so, mitral valve replacement with a S.J.M. 25 mm performed to control MRSA sepsis condition. During operation, we used VCM 2 g into the extracorporeal circulation and after operation 0.5 g intravenously every 6 hours. Two weeks later we changed antibiotics to FOM, Viccillin and ABK according to the result of minimum inhibitory concentration (MIC) obtained through blood culture. The patient was discharged on the 44 th postoperative day because of her uneventful postoperative course.

[Healthcare associated infection: emerging problem in a neurology department].

Healthcare-associated infection (HAI) is, nowadays, a serious problem, contributing a lot to the burden of the hospital stays. Its impact is really huge and the study of these matters is taking a growing interest. To compare, in terms of HAI, the current Neurology Department (localized inside the building of Hospital Geral) and the oldest one, which was far away from the institutional campus. To identify difficulties regarding the management of HAI, trying to propose measures for quality improvement. We revised the clinical files of the patients with HAI documented by culture, on a homologue period of 6 months. Variables like more frequently isolated microorganisms, antibiotics sensibilities, patients' comorbidities, treatment adequacy and duration of hospitalization were analyzed. In the oldest Department, 23 patients were identified, 8 men (mean +/- 2SD: 80.4 +/- 9.04 years old) and 15 women (77.3 +/- 21.28 years old), with positive microbiological studies (51). Ischemic stroke caused 73.9% of these hospitalizations. Escherichia coli - EC - (27%), methicillin-resistant Staphylococcus aureus - MRSA - (22%) and Klebsiella pneumoniae - KP - (10%) were the most frequently identified microorganisms in the biological samples studied (sputum, urine, blood, urethral exudate and eschar). Amoxicillin/clavulanic acid was the most empirically used antibiotic (only effective on 37% of the cases, according to the sensibility tests). Hospitalizations had an average of 22 days and 1.3 antibiotics per patient were used. At discharge, Rankin had a mode of 5. In the current Department, 46 patients were studied, 22 men (76.4 +/- 22.6 years old) and 24 women (74.1 +/- 32.6 years old), having 119 positive cultures. Again, ischemic stroke caused the majority of the admissions (52.2%). MRSA (26%), Pseudomonas aeruginosa - PA - (17%) and EC (17%) were the most prevalent pathogens (the same biological products were studied, plus lingual exudates and central venous catheter tips). Ciprofloxacin was the most used antibiotic (suitable on 75% of the cases). Internments had an average of 24.3 days and, this time, 2.5 antibiotics were used per patient, by mean. At discharge, Rankin evaluation had again a mode of 5. Despite the taken measures and change in facilities, HAI had really increased in the Neurology Department. Since human resources are the same, we think are important, as possible aggravating conditions, space restriction and ward sharing with patients of other medical specialities, as it happens in the current Department. More aggressive pathogens require a rapid and comprehensive intervention, in order to minimize its impact on daily clinical practice and in the management of hospital stays.

Linezolid for the treatment of community-acquired pneumonia in hospitalized children. Linezolid Pediatric Pneumonia Study Group.

To determine the safety, tolerance, pharmacokinetics and efficacy of linezolid, a new oxazolidinone antibiotic in the treatment of community-acquired pneumonia in hospitalized children. A Phase II, open label multicenter study of intravenous linezolid followed by oral linezolid suspension, both at a dose of 10 mg/kg every 12 h. Efficacy was assessed at 7 to 14 days after the last dose of linezolid. Children 12 months to 17 years old with community-acquired pneumonia admitted to the hospital of 14 participating centers. From July 21, 1998, through May 14, 1999, 79 children were enrolled and 78 received linezolid. Sixty-six children completed treatment and follow-up and were evaluable for clinical outcome. The median age of the evaluable patients was 3 years (range, 1 to 12 years); 47 were 2 to 6 years old. Pathogens were isolated from blood or pleural fluid cultures in 8 children: Streptococcus pneumoniae, 6 (2 penicillin-resistant); Group A Streptococcus, 1; methicillin-resistant Staphylococcus aureus, 1. Chest tubes were placed in 9 patients. The mean total duration of intravenous and oral administration was 12.2 +/- 6.2 days (range, 6 to 41 days). The mean peak and trough plasma concentrations of linezolid were 9.5 +/- 4.8 and 0.8 +/- 1.2 microg/ml, respectively. At the follow-up visit 7 to 14 days after the last dose of linezolid, 61 patients (92.4%) were considered cured including all the patients with proven pneumococcal pneumonia, one failed (methicillin-resistant Staphylococcus aureus) and 4 were considered indeterminate. The most common adverse effects in the intent to treat group were diarrhea (10.3%), neutropenia (6.4%) and elevation in alanine aminotransferase (6.4%). Linezolid was well-tolerated and could be considered an alternative to vancomycin for treating serious infections caused by antibiotic-resistant Gram-positive cocci in children pending results of additional studies.

[Fever, negative blood culture findings and absence of response to antibiotic therapy in a patient after a second aortic valve prosthesis].

A 53-year-old patient had a prosthetic valve (St. Jude Medical 25) 9 years ago because of a Staphylococcus aureus endocarditis with severe aortic regurgitation. An initially mild, progressively more severe, aortic regurgitation then developed as a result of an empty paravalvular abscess cavity, requiring another valve replacement. Fever started on the 3rd postoperative day and persisted despite combined treatment with beta-lactam antibiotics and aminoglycoside. At first no infectious focus could be identified radiologically or by echocardiography. But transoesophageal echocardiography revealed vegetations in the old abscess cavity. Several blood cultures were negative, while serological tests gave markedly raised antibody titers against Coxiella burnetii. Assuming Coxiella burnetii endocarditis the patient was given doxycycline, 2 x 100 mg daily and cotrimoxazole, 1 x 960 mg daily. The fever subsided and the vegetations had disappeared after four weeks. Because of the high risk of recurrence the antibiotic treatment was to be continued for two years. Coxiella burnetii should be considered as a possible cause of fever of unknown origin, especially in patients with existing or operated cardiac valvar defects, when endocarditic vegetations have been demonstrated and several blood cultures have been negative.

Antibiogram for haemodialysis catheter-related bloodstream infections.

Background. Haemodialysis (HD) catheter-related bloodstream infections (CRBSIs) are a major complication of long-term catheter use in HD. This study identified the epidemiology of HD CRBSIs and to aid in the choice of empiric antibiotics therapy given to patients with HD CRBSIs. Methods. Patients with HD CRBSIs were identified. Their blood cultures were performed according to standard sterile technique. Specimens were sent to the microbiology lab for culture and sensitivity testing. Results were tabulated in antibiograms. Results. 18 patients with a median age of 61.0 years (IQR: 51.5-73.25) were confirmed to have HD CRBSIs based on our study criteria. Eight (44.4%) patients had gram-negative infections, 7 (38.9%) patients gram-positive infections, and 3 (16.7%) patients had polymicrobial infections. We noted that most of the gram-negative bacteria were sensitive to ceftazidime. Unfortunately, cloxacillin resistance was high among gram-positive organisms. Coagulase-negative Staphylococcus and Bacillus sp. were the most common gram-positive organisms and they were sensitive to vancomycin. Conclusion. Our study revealed the increased incidence of gram-negative organism in HD CRBSIs. Antibiogram is an important tool in deciding empirical antibiotics for HD CRBSIs. Tailoring your antibiotics accordingly to the antibiogram can increase the chance of successful treatment and prevent the emergence of bacterial resistance.

Etiologic diagnosis and clinical treatment of multiple drug-resistant bacteria infection in elderly patients with stroke-associated pneumonia after neurosurgery.

Our objective is to analyze the etiology and antibiotics resistance rate of multiple drug-resistant bacteria infection in elderly patients with stroke-associated pneumonia from Neurosurgery Department, providing a reference for clinical treatment. Sputum of 372 elderly patients with stroke-associated pneumonia (SAP) from Neurosurgery Department was collected for sputum culture and drug sensitivity test, and pathogenic bacteria distribution and drug resistance rate of antibiotics were discussed. Among 372 pathogenic bacteria, there were 95 cases with Gram-positive cocci, the percentage was 15.32 %; there were 277 cases with Gram-negative bacilli, the percentage was 59.95 %; there were 54 cases with fungus, the percentage was 14.51 %; the common Gram-positive cocci included Staphylococcus aureus, Staphylococcus haemolyticus and Staphylococcus epidermidis, with percentages of 15.32 %, 2.96 % and 4.30 % respectively; the common Gram-negative bacilli included Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae, with percentages of 23.92 %, 14.25 % and 9.95 % respectively; the highest drug resistance rates of Staphylococcus aureus were 100.00 % to penicillin, erythrocin and oxacillin, the highest drug resistance rate of Staphylococcus epidermidis was 87.50 % to erythrocin, the highest drug resistance rate of Staphylococcus haemolyticus was 100.00 % to penicillin and erythrocin, the lowest drug resistance rates of three Gram-negative bacilli were 0 % to teicoplanin and vancomycin; the highest drug resistance rates of Escherichia coli were 100.00 % to ceftriaxone and ticarcillin, and the lowest drug resistance rate was 11.32 % to ciprofloxacin; the highest drug resistance rate of Pseudomonas aeruginosa was 100.00 % to ceftriaxone, and the lowest drug resistance rate was 22.47 % to imipenem; the highest drug resistance rate of Klebsiella pneumoniae was 81.08 % to aztreonam, and the lowest drug resistance rate was 0.00 % to imipenem. Stroke-associated pneumonia is common clinically in elderly patients from Neurology Department, the early-stage and rational use of antibiotics should be applied according to the etiologic distribution and drug resistance characteristics. Meanwhile, prevention measures should be applied.

Successful treatment of disseminated cerebritis complicating methicillin-resistant Staphylococcus aureus Endocarditis unresponsive to vancomycin therapy with linezolid.

A unique case of community acquired methicillin resistant Staphylococcus aureus (MRSA) sepsis, with endocardial and cerebral metastatic seeding, caused by a strain representative of the Italian clone, is described. The patient was a 47-y-old man without apparent risk factors for endocarditis and for MRSA infection who developed coma with multiple cerebritis lesions under vancomycin plus amikacin therapy. He was eventually cured with the addition of linezolid to the initial antimicrobial regimen. This observation seems to confirm previous reports of the efficacy of linezolid for the treatment of central nervous system infections caused by multidrug resistant Gram-positive bacteria. To our knowledge, this is the first report of MRSA disseminated cerebritis, a nearly always fatal disease, cured with this oxazolidinone drug. The increase in community acquired MRSA may have some impact on empirical treatment of serious infections caused by this organism.

Infective endocarditis caused by Streptococcus acidominimus.

A case of infective endocarditis caused by Streptococcus acidominimus is reported. An 81-year-old Caucasian man underwent an elective transcatheter aortic valve implantation due to his severe aortic valve stenosis. He presented to the hospital 3 weeks later with a 1-week history of fever (39ºC) that did not resolve following a 3-day course of azithromycin and a 5-day course of ciprofloxacin. Three sets of blood sample cultures were taken. Empirical antimicrobial treatment was initiated to target gram-positive and gram-negative microorganisms and consisted of vancomycin 1 g intravenous (i.v.) every 12 hours and imipenem-cilastatin 500 mg i.v. every 6 hours. After 48 hours, the blood culture was positive for S. acidominimus. The strain was sensitive to ampicillin, cephalosporins, tetracycline, and vancomycin. It was resistant to penicillin, macrolides, trimethoprim-sulfamethoxazole, and fosfomycin. Transesophageal echocardiography showed a small mobile vegetation attached to the anterior mitral valve leaflet, along with mild mitral regurgitation. The patient was diagnosed with native mitral valve infective endocarditis, and imipenem-cilastatin was discontinued. The patient showed clinical and laboratory improvement during his 2-week hospitalization. A peripherally inserted central catheter was put in place, and the patient was discharged on i.v. vancomycin to complete a total of 6 weeks treatment, after which the infection resolved. An 81-year-old man diagnosed with mitral valve endocarditis caused by S. acidominimus was successfully treated with vancomycin.

Pattern and Sensitivity of Bacterial Colonization on the Tip of Non-Tunneled Temporary Hemodialysis Catheters: Results of a Tertiary Hospital in Somalia.

Bacterial colonization on the tip of non-tunneled temporary hemodialysis catheters (NTHCs) and associated catheter-related infections (CRI) is a common complication in hemodialysis (HD) patients. In this study, we aimed to investigate the pattern of bacterial colonization formed on the tip of non-tunneled temporary hemodialysis catheters and their antibiotic sensitivity. This retrospective analysis was performed in the HD unit of an Education and Research Hospital that follows up a universe of approximately 300 patients, primarily from Mogadishu, Somalia. From September 2020 to September 2021, a total of 137 temporary HD catheters were removed and their tips were sent for culture after there was a suspicion of CRI and other sources of infection were excluded. HD Catheter tips were cultured semi-quantitatively, and the antibiogram of the positive cultures was studied. Gram-positive cocci were found to be the most predominant bacterial organisms in positive cultures with 27 (31.0%) for <iStaphylococcus aureus</i, 9 (10.3%) for <iStaphylococcus haemolyticus</i and 5 (5.7%) for <iStaphylococcus epidermidis</i. We found Enterococci to be 5.7% of the isolated microorganisms. Gram-negative pathogens isolated included <iEscherichia coli</i 13 (14.9%) as the most common, followed by <iKlebsiella pneumoniae</i 10 (11.5%) and <iAcinetobacter baumannii</i (4.6%). Methicillin-resistant <iStaphylococcus aureus</i (MRSA) was found to be 9.4%. Gram-positive isolates showed high sensitivity (100%) to Linezolid, Daptomycin, Vancomycin, and Tigecycline, but a low sensitivity rate to Oxacillin (41.2%). Gram-negative isolates had the highest sensitivity to Tigecycline (100%), Imipenem (88.9%), and Amikacin (87%) but low sensitivity to Ampicillin (4.8%), Trimethoprim/Sulfamethoxazole (TMP-SMX) (23.1%), and Ceftazidime (7.1%). We conclude that each institution should have its own antibiogram in the management of HD CRIs. According to our findings in this study, we recommend intravenous Vancomycin and Imipenem as empirical therapy in patients with suspected HD CRIs.

Panton-Valentine leukocidin-positive novel sequence type 5959 community-acquired methicillin-resistant Staphylococcus aureus meningitis complicated by cerebral infarction in a 1-month-old infant.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a pathogen of major importance in pediatric patients. CA-MRSA can cause skin and soft tissue infection in children and young active adults with no predisposing factors, and life-threatening infections such as meningitis or necrotizing pneumonia have been reported. We report here a case of CA-MRSA meningitis complicated by acute left middle cerebral artery (MCA) infarction and necrotizing pneumonia in a previously healthy 1-month-old Vietnamese boy. He was firstly treated with vancomycin, but changed to linezolid because of persistent fever and low vancomycin trough level. He recovered successfully with residual right-sided hemiparesis. The mode of transmission of CA-MRSA and the mechanism of cerebral infarction (thrombotic or embolic) were unknown. The isolate was genotyped as staphylococcal cassette chromosome (SCC) mec type V with a novel sequence type (ST) 5959 harboring the Panton-Valentine leukocidin (PVL) gene. ST 5959 is a double locus variant of ST 59, which is a major PVL-positive CA-MRSA strain isolated in invasive disease in Asian countries. This case report may serve as a warning about the dissemination of PVL-positive CA-MRSA in and around Japan, with the possibility of causing serious life-threatening disease. The potential of linezolid for the treatment of MRSA meningitis as one of the alternative MRSA therapeutic drugs is also discussed.

[Cathether related blood stream infection in ICU patients with prolonged central venous catheterisation--cause and prevention].

Colonization of the tip of the intravenous catheter is often observed in the ICU practice and can be the source of dangerous bacteriemia (CRBSI--catheter related bloodstream bacteraemia) and sepsis with multiorgan failure. There are many cases conected with bacterial colonization of the tip of the catheter in the ICU practice, which could be the source of dangerous bacteriemia--CRBSI (catheter related bloodstream bacteriemia) and sepsis with organs failure. 105 patients with sepsis were examined, which clinical state pointed, that CVC was the source of infection. We removed the CVC in this patient, and its tip and patient's blood were examined microbiologically. In the case of positive result, the antibiogram was made. Evaluation of colonisation and infections of central venous catheters and catheter related blood stream infections (CRBSI) in general ICU patients' and with identification of most frequent microorganisms and their antibiotic sensibility. Results. After examining of 105 samples in 37 (35, 24%) cases we did not culture bacteria. From the rest of 68 (64, 76%) samples we cultured 110 bacterial colonies. 8 of them were admitted to be contaminated samples. 60 tips of the catheter were used to proper analysis from which we isolated 102 bacterial colonies: 44 (43.1%) Gram positive cocci, 32 (31.5%) Enterobacteriaceae, 23 (22.5%) glucose non-fermentative gram-negative rods rods Gram negative non glucose fermentation and 3 (2.9%) fungi (C. albicans). We analized 60 blood samples that derived from patients with confirmed catheter colonisation. It was found that 8 blood samples indicated bacteriemia, but only in 2 cases isolated bacteria came from the CVC. Conclusions. (1) The majority of central venous catheters on ICU are colonized by pathogenic microorganisms. (2) Aerobic Gram positive and Gram negative bacteria are responsible for CVCs' infection. (3) Bacterial colonization of CVCs' is not very often the reason of CRBSI. (4) Prolonged use of central venous catheters needs careful prophylactic standards of an microbiological monitoring.

Brain abscess after stent-assisted coiling for ruptured middle cerebral artery aneurysm.

A 24-year-old man was admitted with sudden severe headache. Brain computed tomography (CT) revealed a subarachnoid hemorrhage in the basal cistern and both Sylvian cisterns and a left internal carotid artery angiogram showed a small aneurysm on the bifurcation of the left middle cerebral artery. We performed Y-configured stent-assisted coil embolization. On the fifth post-embolization day, the patient had chills, and his body temperature was over 38℃. Staphylococcus aureus was cultured from the venous blood sample. Central venous catheter-induced bacteremia was suspected. The central venous catheter was immediately removed, and an antibiotic to which the organism was susceptible (nafcillin) was injected for 15 days according to the result of the antibiotics sensitivity test. He was discharged without any clinical or neurological symptoms on the 32nd hospital day. Three months after treatment, the patient complained in the outpatient department of headache, nausea and vomiting. Brain magnetic resonance imaging showed several well-rimmed enhancing lesions in the left temporoparietal lobe. The headache, nausea and vomiting was aggravated, and brain CT showed more enlarging cysts and aggravation of the midline shift. Stereotactic aspiration was performed for the three biggest cysts, and greenish-white colored pus was aspirated. The identified pathogen was methicillin-sensitive Staphylococcus aureus in the culture study. Vancomycin and ceftriaxone were administered intravenously for three weeks, followed by intravenous injection of nafcillin for five weeks. The patient's postoperative course was clinically uneventful, and brain CT on postoperative day 57 showed total disappearance of the rim-enhanced abscess.

Emerging Trends of Bloodstream Infections: A Six-Year Study at a Paediatric Tertiary Care Hospital in Kabul.

To determine the frequency of pathogens causing bloodstream infections and evaluate their trends and antibiogram patterns among in-patients in a paediatric tertiary care centre. Descriptive study. French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan in two phases, from January 2010 to December 2015. Results of blood cultures from suspected cases of sepsis admitted in the FMIC, from January 2010 to December 2012 (Period-1), and from January 2013 to December 2015 (Period-2) were completed. Standard microbiological methods were followed for blood culture and antibiotic sensitivity testing. Out of total 1,040 cases of culture proven sepsis, 528 (50.77%) Gram-negative bacilli (GNB), 474 (45.58%) Gram-positive cocci (GPC), and 38 (3.65%) Candida species were isolated during the entire study period. Out of 528 GNB isolates, 373 (70.64%) belonged to the Enterobacteriaceae and 155 (29.36%) were non-fermenters. Among Enterobacteriaceae, 168 (31.82%) were Klebsiella species (K. pneumoniae=124, K. oxytoca=44), 70 (13.26%) were Enterobacter species (E. cloacae=52, E. aerogenes=18), 65 (12.31%) were E. coli, 37 (7.01%) were Serratia marcescens and 31 (5.87%) were others. Out of 155 non-fermenters, 88 (16.67%) were Pseudomonas aeruginosa, 39 (7.39%) were Burkholderia cepacia and 18 (3.41%) were Stenotrophomonas maltophilia. There was a drop in the frequency of Enterobacteriaceae from 85% in Period-1 to 58.68% in Period-2. There was an increase in the frequency of nonfermenters from 15% to 41.32%, particularly 18 new cases of sepsis caused by Stenotrophomonas maltophilia during Period-2. Among GPC, there was an overall rise of 16.14% in the prevalence of Staphylococcus epidermidis during Period-2 and a drop of 9.64% in the frequency of Staphylococcus aureus during Period-2. The majority of Gram-negative isolates were multidrug-resistant to commonly used antibiotics. However, most of the isolates were sensitive to amikacin and imipenem (except S. maltophilia). The frequency of those producing ESBL reduced by 11.22% during the Period-2. Among Gram-positive cocci, the pattern of antibiogram did not show a significant change during both periods, and majority remained resistant to commonly used antibiotics. All Staphylococci were sensitive to vancomycin but resistant to penicillin. There was a substantial decline of 18.87% in the frequency of Methicillin-resistant Staphylococci (MRSA/MRSE) during Period-2. Staphylococci and Klebsiellae remain the most important bacteria responsible for bloodstream infections in a tertiary healthcare facility in Kabul. Yet, there has been an increase in the prevalence of Pseudomonas and Burkholderia cepacia. Moreover, Stenotrophomonas maltophilia emerged as a new hospital acquired pathogen. This study could possibly help in suggesting choices eluding the misuse of appropriate antibiotics.

Adult Coagulase-Negative Staphylococcal Meningitis in Qatar: Clinical Characteristics and Therapeutic Outcomes.

Coagulase-negative staphylococci (CoNS) have emerged as a major pathogen in nosocomial meningitis. This study was designed to describe the clinical profile, laboratory parameters, treatment, and outcomes of CoNS meningitis in patients admitted to Hamad General Hospital, Qatar. This retrospective hospital-based study described the patients with CoNS meningitis from 2009 to 2013. Twelve patients were recruited for the study, of which there were 10 (83.3%) males and 2 (16.7%) females with a median age of 39 years (interquartile range [IQR]: 29-46 years). Fever was the most common presenting symptom being present in all patients, followed by mental alterations 7 (58.3%). All CoNS meningitis cases in this study were nosocomially acquired after neurosurgery and in most cases after external ventricular drain (EVD) insertion. The median time between the procedure and acquisition of infection was 13 days (IQR: 10-15.7 days). The isolated species include 8 (66.7%) <iStaphylococcus epidermidis</i, 2 (16.7%) <iStaphylococcus capitis</i, and 2 (16.7%) <iStaphylococcus haemolyticus</i. All CoNS isolates were sensitive to vancomycin while 75% of them were oxacillin resistance. In the eight patients with EVDs, the infected EVDs were removed, while all patients received empirical antibiotics involving mainly vancomycin and ceftriaxone that were modified upon receipt of culture results. All patients were cured, and no mortality was reported. CoNS meningitis is a recognized complication related to the introduction of neurosurgical devices. Because of its nonspecific clinical presentation, treating physicians should have a high suspicion index. If CoNS meningitis is highly suspected, vancomycin is the empirical treatment of choice while awaiting results of sensitivity.

[A rarely isolated bacterium in microbiology laboratories: Streptococcus uberis].

Streptococcus uberis is a gram-positive bacterium that is mostly responsible for mastitis in cattle. The bacterium rarely has been associated with human infections. Conventional phenotyphic methods can be inadequate for the identification of S.uberis; and in microbiology laboratories S.uberis is confused with the other streptococci and enterococci isolates. Recently, molecular methods are recommended for the accurate identification of S.uberis isolates. The aim of this report is to present a lower respiratory tract infection case caused by S.uberis and the microbiological methods for identification of this bacterium. A 66-year-old male patient with squamous cell lung cancer who received radiotherapy was admitted in our hospital for the control. According to the chest X-Ray, patient was hospitalized with the prediagnosis of ''cavitary tumor, pulmonary abscess''. In the first day of the hospitalization, blood and sputum cultures were drawn. Blood culture was negative, however, Candida albicans was isolated in the sputum culture and it was estimated to be due to oral lesions. After two weeks from the hospitalization, sputum sample was taken from the patient since he had abnormal respiratory sounds and cough complaint. In the Gram stained smear of the sputum there were abundant leucocytes and gram-positive cocci, and S.uberis was isolated in both 5% sheep blood and chocolate agar media. Bacterial identification and antibiotic susceptibility tests were performed by VITEK 2 (Biomerieux, France) and also, the bacterium was identified by matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) based VITEK MS system as S.uberis. The isolate was determined susceptible to ampicillin, erythromycin, clindamycin, levofloxacin, linezolid, penicillin, cefotaxime, ceftriaxone, tetracycline and vancomycin. 16S, 23S ribosomal RNA and 16S-23S intergenic spacer gene regions were amplified with specific primers and partial DNA sequence analysis of 16S rRNA polymerase chain reaction (PCR) products were performed by 3500xL Genetic Analyzer (Applied Biosystems, USA). According to the partial 16S rRNA gene sequencing results, bacterium was confirmed as S.uberis. This report makes a significant contribution to the number of case reports of human infections caused by S.uberis as the identification was performed by current microbiological methods in our case. In conclusion, S.uberis should be evaluated as an opportunistic pathogen among the immunosuppressed patients and in addition to phenotypic bacteriological methods, the other recent microbiological methods should also be utilized for the identification.

The First Case Report of Community-Acquired Infective Endocarditis Due to Sequence Type 1223 <i>Staphylococcus argenteus</i> Complicated with Convexity Subarachnoid Hemorrhage.

<iStaphylococcus argenteus</i is a new species classified as part of the <iStaphylococcus aureus</i-related complex in 2015 and has been recognized to be as pathogenic as <iS. aureus</i. We describe the first case of endocarditis caused by <iS. argenteus</i. A 51-year-old man presented with chief complaints of fever and headaches. On admission, he showed a slight decrease in consciousness level (Glasgow Coma Scale, E4V4M6). Careful physical examination and imaging revealed a systolic heart murmur, Janeway lesions, and complicating convexity subarachnoid hemorrhage (cSAH) of the left frontal lobe. Ceftriaxone 4 g/day was administered immediately after blood cultures were obtained. The next day, all blood cultures grew Gram-positive cocci, identified as <iStaphylococcus aureus</i or <iStaphylococcus argenteus</i by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). However, the version of MALDI-TOF MS used could not distinguish these bacteria. Although we could not find valvular vegetation, he was clinically diagnosed with infective endocarditis according to the modified Duke's criteria. Meropenem 6 g/day and linezolid 1.2 g/day were started to cover <iS. aureus</i and methicillin-resistant <iS. aureus</i. Finally, ampicillin was selected based on drug susceptibility, and the patient was treated for 8 weeks and recovered without permanent damage. The isolated strain formed white colonies on blood agar plates, characteristic of <iS. argenteus</i, and differs from golden colony-forming <iS. aureus</i. Genetic analysis revealed the isolated strain as <iS. argenteus</i (sequence type 1223). Although distinguishing <iS. argenteus</i from <iS. aureus</i using routine conventional laboratory tests is difficult, the updated library version of MALDI-TOF MS is useful in identifying <iS. argenteus</i. Interestingly, all published cases of infection caused by ST1223 have been reported in Japan. Therefore, the trend of infections from the ST1223 strain should be carefully monitored, particularly in Japan. Further investigation is needed to clarify the epidemiology and clinical characteristics of <iS. argenteus</i infection, as there are few studies regarding this pathogen.

Bacterial incidence and antibiotic sensitivity pattern in moderate and severe infections in hospitalised patients.

Infectious diseases are among the leading causes of death and sometimes curable. Bacteria are the most common aetiology in hospitalised patients. Objectives of this study were to evaluate the incidence of bacterial infections and their pattern of susceptibility to antibiotics in moderate and severe infections in hospitalised patients. The study was performed in the apical teaching hospital of West Bengal in the first half of 2005. Patients admitted in medical wards and medical ICU, suffering from moderate and severe infections having APACHE-II score > 5 were studied. Clinical evaluation, routine and specific investigations were done in each case. Microbiological samplings were tried on day 1, after completion of antibiotic therapy and in between as required. Aerobic BACTEC bacterial culture and sensitivity tests were done. Pending initial culture and sensitivity report empiric antibiotic therapy was started, which was modified on getting the culture and sensitivity report. Outcome was observed as no response, cured, resolved, inconclusive, died and left against medical advice. Out of 40 patients total number of samples were 54 and that of sites of infections were 48. Primary site could not be detected in 11 infections (22.9%). Commonest form was urinary tract infection and abdominal infection in community acquired infection (n=18) and pneumonia in hospital acquired infection (n = 15). Culture was positive in 33 (61.11%), Gram-negative infection was more common in general, but incidence of Gram-positive infection was also quite high and Gram-positive infection was more common in community acquired infection. In general S aureus was most common bacteria -8 (24.24%). In community acquired infection S aureus 4 (22.22%) predominated followed by E coli and in hospital acquired infection S aureus -4 (26.66%) followed by E coli and P aeruginosa. Incidence of methicillin resistant Staph aureus was low. But it constituted 50% of S aureus. No methicillin resistant Staph aureus was found in community acquired infection. Two isolates of vancomycin intermediate sensitive Staph aureus were observed. Methicillin resistant Staph aureus showed maximum sensitivity to linezolid (100%) and all methicillin resistant Staph aureus but one vancomycin intermediate sensitive Staph aureus were sensitive to vancomycin. Coagulase negative Staph aureus were all sensitive to vancomycin and linezolid. Gram-negatives were mostly resistant to aminoglycosides and P aeruginosa were all sensitive to aztreonam. Single strain of S typhi as isolated was resistant to ceftriaxone and ciprofloxacin. P miribalis, P aeruginosa and coagulase negative Staph aureus were notoriously multidrug resistant; 82.5% of cases responded to treatment of which 35% were cured microbiologically. Gram-negative infection was more common overall, but incidence of Gram-positive infection was also very high. Gram-negative infections were responsible for more severe infections and case fatality. Multidrug resistant Gram-positive infections are rising.

[A case of cerebral abscess due to methicillin-resistant Staphylococcus aureus which is treated with linezolid + rifampin combination].

Methicillin-resistant Staphylococcus aureus (MRSA) is a rare cause of cerebral abscesses, however it is a relatively more common etiologic agent in post-neurosurgical abscesses and the main antibacterial therapy option is vancomycin. In this report, a case of brain abscess due to MRSA which did not respond neither to moxifloxacin + vancomycin nor vancomycin + rifampin combination therapies, and merely treated by linezolid + rifampin combination, has been presented. Fifty-one years old female patient who was operated 40 days ago for subarachnoid bleeding and aneurysm in middle cerebral artery bifurcation, was hospitalized due to purulent leakage from the operation area. She did not have fever and her physical examination, including the neurologic system, was normal. Computerized tomography revealed an approximately 1 cm lesion compatible with subdural empyema and cerebral abscess in the right frontoparietal area in supratentorial sections. The patient was operated for wound revision and moxifloxacin was initiated. Since the operation materials revealed MRSA growth, vancomycin (4 x 500 mg, IV) was added to the treatment. The isolate was identified by conventional methods, and antibiotic susceptibility test performed by disk diffusion method showed that it was susceptible to levofloxacin, linezolid, rifampin, vancomycin and teicoplanin. Since no clinical response was obtained in two weeks, moxifloxacin was switched to rifampin (300 mg 1 x 2). On the 10th day of vancomycin + rifampin therapy, radiological findings showed development of cerebritis and therefore vancomycin was changed with linezolid (2 x 600 mg, IV). The control CT of the patient revealed regression of the brain lesion and linezolid + rifampin treatment continued for six weeks. The patient did not develop any hematological, liver or renal toxicity during the therapy and the radiological findings regressed. No relapse were detected in the one year follow-up period. This case suggested that linezolid might be a treatment alternative in the therapy of vancomycin-refractory MRSA brain abscess.


Of the proposed drugs, the least likely options would be 3, since metformin very rarely causes lingual angioedema (in March 2020 there was only one case described worldwide) and 4, since, among the adverse reactions of levodopa, angioedema is classified among the very rare ones (frequency less than 0.1%). Of the two remaining options, the drugs most frequently and classically associated with lingual angioedema are ACE inhibitors (frequency around 0.2%), and their association with simvastatin is also less than 0.1%.

Of the proposed drugs, [HIDDEN] since metformin very rarely causes lingual angioedema (in March 2020 there was only one case described worldwide) and [HIDDEN], since, among the adverse reactions of levodopa, angioedema is classified among the very rare ones (frequency less than 0.1%). Of the two remaining options, the drugs most frequently and classically associated with lingual angioedema are ACE inhibitors (frequency around 0.2%), and their association with simvastatin is also less than 0.1%.

A 72-year-old patient presents to the emergency department with severe lingual angioedema. She has no associated urticaria and no history of drug or food allergy. His personal history includes type 2 diabetes mellitus, dyslipidemia, hypertension, hypothyroidism and Parkinson's disease. In regular treatment with metformin, simvastatin, enalapril, thyroxine and levodopa. Which of the following drugs is most likely the causal drug of the clinical picture described?

[Therapeutic behavior to follow in the following clinical case: treatment of type 2 diabetes].

A 62-year old woman with obesity, high blood pressure and type 2 diabetes mellitus (DM2) was referred to a Vascular Risk Unit of the Internal Medicine Department due to elevated HbA1C (8.1%) in spite of having taken metformin (850 mg/12h) and glipizide (10 mg/12 h) regularly. She tries to exercise daily (walking 30 min) and has lost weight (from 5 to 12 kg) several times, but always regains what she has lost. Furthermore, she monitors her glucose levels in fasting every two weeks and generally has between 120 and 160 mg/dL. Her high blood pressure is being treated with enalapril/HCTZ and she also takes aspirin 100mg/day and simvastatin 20 mg/day. It is seen in her family background that one brother died suddenly at 50 years of age. Her physical examination shows a BMI of 32.4 Kg/m(2), and she has no edemas in the lower limbs. Her BP is 154/82 mmHg and creatinine 0.9 mg/dL. She has no microalbuminuria and her liver function is normal. What treatment do you think would be the more appropriate? 1 - Add glitazones. 2 - Add incretin mimetics (GLP 1/ DPP-4). 3 - Slow acting insulin.

History of Parkinson's disease

with Parkinson's disease resulting from treatment with levodopa was published in 1968. Levodopa brought about a revolution in the management of PD. By the late 1980s deep brain stimulation introduced by Alim-Louis Benabid and colleagues at Grenoble, France, emerged as a possible treatment and it was approved for clinical use by the FDA in 1997.

Levodopa (L-Dopa) -- Contraindications

Per the Food and Drug Administration (FDA)  label, Levodopa should not be used in patients with a history of malignant melanoma due to the risk of activating melanoma. However, several studies suggested drug exposure is not the reason for the increased risk of melanoma but may reflect the association of Parkinson disease with melanoma. More studies are required to verify the correlation between levodopa and dermatologic effects. [17]

Dopamine dysregulation syndrome

Management First choice management measure consists in the enforcement of a dopaminergic drug dosage reduction. If this decrease is maintained, dysregulation syndrome features soon decrease. Cessation of dopamine agonists therapy may also be of use. Some behavioral characteristics may respond to psychotherapy; and social support is important to control risk factors. In some cases antipsychotic drugs may also be of use in the presence of psychosis, aggression, gambling or hypersexuality. Based upon five case reports, valproic acid may have efficacy in controlling the symptoms of levodopa-induced DDS that arise from the use of levodopa for the treatment of Parkinson's disease. Epidemiology DDS is not common among PD patients. Prevalence may be around 4%. Its prevalence is higher among males with an early onset of the disease. Previous substance abuse such as heavy drinking or drug intake seems to be the main risk factor along with a history of affective disorder. History

InternalMed_Harrison

Centrally acting anticholinergic drugs such as trihexyphenidyl and benztropine were used historically for the treatment of PD, but they lost favor with the introduction of dopaminergic agents. Their major clinical effect is on tremor, although it is not certain that this benefit is superior to what can be obtained with agents such as levodopa and dopamine agonists. Still, they can be helpful in individual patients with severe tremor. Their use is limited particularly in the elderly, due to their propensity to induce a variety of side effects including urinary dysfunction, glaucoma, and particularly cognitive impairment. Carbidopa/levodopa 10/100, 25/100, 25/ 200–1000 mg 250 mg levodopa/d 2–4 times/d Benserazide/levodopa 25/100, 50/200 mg Carbidopa/levodopa CR 25/100, 50/200 mg Benserazide/levodopa 25/200, 25/250 mg MDS Parcopa 10/100, 25/100, 25/250 Carbidopa/levodopa/ 12.5/50/200, entacapone 18.75/75/200, 25/100/200, 31.25/125/200, 37.5/150/200, 50/200/200 mg

InternalMed_Harrison

Therapy with colchicine, para-aminosalicylate, neomycin, slow-release potassium chloride, anticonvulsant drugs, metformin, phenformin, cytotoxic drugs Alcohol in close relatives and in persons with other organ-specific autoimmune diseases, e.g., thyroid diseases, vitiligo, hypoparathyroidism, and Addison’s disease. It is also associated with hypogammaglobulinemia, with premature graying or blue eyes, and persons of blood group A. An association with human leukocyte antigen (HLA) 3 has been reported in some but not all series and, in those with endocrine disease, with HLA-B8, -B12, and -BW15. Life expectancy is normal in women once regular treatment has begun. Men have a slightly subnormal life expectancy as a result of a higher incidence of carcinoma of the stomach than in control subjects. Gastric output of hydrochloric acid, pepsin, and IF is severely reduced. The serum gastrin level is raised, and serum pepsinogen I levels are low.

Extrapyramidal side effect of donepezil hydrochloride in an elderly patient: A case report.

Alzheimer disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction, which is mainly manifested as memory impairment and a reduced ability to self-care, often accompanied by neuropsychiatric and behavioral disorders. Donepezil is the second drug to be approved by the US FDA for the treatment of AD. Of the five FDA-approved drugs for AD treatment, donepezil is currently the most widely used. Here, we report an extrapyramidal adverse reaction to donepezil in an elderly patient with AD. An 87-year-old woman presented with a 1-year history of forgetfulness that was aggravated since the past 2 months. She had a long-term history of multiple major conditions, including hypertension, diabetes, osteoporosis, and arterial plaques. Brain imaging showed age-related changes, and her Mini Mental State Examination score was 20. Other tests revealed no abnormalities apart from multiple thyroid nodules on ultrasonography. She was diagnosed with AD, hypertension, type 2 diabetes mellitus, diabetic neuropathy, osteoporosis, carotid and lower-extremity arterial plaques, thyroid nodules. She was treated with donepezil (5 mg/day), amlodipine besylate (5 mg/day), glimepiride (4 mg/day), methylcobalamin (1.5 mg/day), calcium carbonate D3 (600 mg/day), simvastatin (20 mg/day) and enteric-coated aspirin (100 mg/day). Four days later, she experienced fatigue, panic, sweating, and one episode of vomiting. On the 5th day, she developed increased muscle tension, speech difficulty, and involuntary tremors. Imaging and blood tests revealed no obvious abnormality, and the patient was not receiving psychotropic drugs. An extrapyramidal adverse reaction to donepezil was considered, and the drug was discontinued, after which the symptoms gradually disappeared. Serious adverse reactions to donepezil can occur in elderly patients, who typically require multiple medications for a variety of comorbidities. In particular, extrapyramidal reactions have occurred when donepezil is administered in combination with psychotropic drugs. However, in our patient, an extrapyramidal adverse reaction occurred in the absence of psychotropic drugs. Thus, clinicians must be aware of inter-individual differences in drug actions and possible serious adverse reactions, and carefully monitor these patients to ensure the timely detection of adverse events and their safe treatment.

Levodopa-induced dyskinesia

Nicotine (administered by dermal adhesive patches) has also been shown to improve Levodopa-induced dyskinesia and other PD symptoms. Patients with prominent dyskinesia resulting from high doses of antiparkinsonian medications may benefit from deep brain stimulation (DBS), which may benefit the patient in two ways: 1) DBS theoretically allows a reduction in l-DOPA dosage of 50–60% (tackling the underlying cause); 2) DBS treatment itself (in the subthalamic nucleus or globus pallidus) has been shown to reduce dyskinesia. Mavoglurant is also currently studied by Novartis for the treatment of this disease. On August 24, 2017 the FDA approved a drug to treat levodopa-induced dyskinesia for Parkinson's patients. The drug, Gocovri, is amantadine manufactured by Adamas Pharmaceuticals. It is the first FDA approved treatment for this condition. References External links Parkinson's disease

History of Parkinson's disease

History of treatments

Sitagliptin/simvastatin

History In 1991, Merck & Co's simvastatin was approved as an HMG-COA inhibitor to lower the levels of LDL cholesterol. In 2006, Merck & Co's sitagliptin was approved by the FDA for treatment of diabetes mellitus type 2. The patent for simvastatin expired in 2006 and many companies began to create a generic product of simvastatin. By creating a combined-dosage form of simvastatin and sitagliptin, Merck was able to increase their sales of simvastatin while meeting the need of patients who take both simvastatin and sitagliptin. Regulation Juvisync was the first product to combine a cholesterol lowering drug with a type 2 diabetes drug in the same tablet. Due to the potential for patients to need different doses of the two drugs, different dosage strengths were approved. These doses are for sitagliptin/simvastatin of 100 mg/10 mg, 100 mg/20 mg, 100 mg/40 mg, 50 mg/10 mg, 50 mg/20 mg, or 50 mg/40 mg. Nonclinical toxicology

[Parkinsonism probably induced by manganese].

In all cases of young persons with clinical Parkinson s disease it should be suspected that it is secondary to some primary disorder. Therefore a battery of diagnostic tests should be done before classification as idiopathic Parkinson s disease. A 31 year old woman whose only previous illness had been Graves disease. She complained of difficulty with movements of her right arm and leg for some months (she had problems with walking and with rapid, repeated movements of her right hand). She also complained of tremor of her right limbs at rest. She denied taking drugs, having dysphagia, dysarthria, visual changes or sphincter disorders. Neurological examination showed her to have monotonous speech, slight facial hypomimia, slight reduction in spontaneous blinking, walking with less swing of her right arm; postural tremor of both arms, worse on the right; bradykinesia (2/4) of both right limbs and rigidity (1/4), axial and of the right limbs. The results of all the investigations done to rule out secondary Parkinsonism were normal, except for the plasma manganese level which was raised, although it returned to normal when the probable source of exposure to this metal was removed. However, the alterations of movement only disappeared after treatment with levodopa was started. In cases of Parkinsonism in young adults secondary causes should always be rules out, such as exposure to certain metals.

Carbidopa/levodopa/entacapone

Carbidopa/levodopa/entacapone may be combined with the drugs rasagiline or selegiline. These drugs are a different type of MAO inhibitor known as selective MAO inhibitors that are often prescribed for Parkinson's disease. Many drug interactions involving selegiline are theoretical, primarily based on interactions with non-selective MAO inhibitors; at oral doses the risk of these interactions may be very low. However, transdermal selegiline, known by its trade name Emsam, is still contraindicated. Transdermal selegiline results in higher plasma levels at which it behaves like a non-selective MAO inhibitor. Concominant use of entacapone, a component of carbidopa/levodopa/entacapone, with MAO inhibitors may increase toxicity of MAO inhibitors. Levodopa, also a component of carbidopa/levodopa/entacapone, in combination with MAO inhibitors may result in hypertensive reactions. Mechanism of action

L-DOPA

History

Dihydroergocryptine

The relatively long half-life and lack of dietary influence of dihydroergocriptine is considered to contribute to the compound's effectiveness in Parkinson's disease, particularly since it allows for more continuous stimulation of brain dopaminergic receptors than short-acting drugs such as levodopa. DHEC is also proven to be a safe and effective in improving symptoms in Parkinson's patients. Motor improvements in Parkinson's patients are usually observed in patients who take at least a mean daily dose of approximately 40 mg. Patients on DHEC demonstrate a better score than if they were on levodopa on the Webster scale, a standardized rating scale of Parkinson's Disease symptoms such as gait parameters and dyskinesia. Another clinical study has shown that DHEC had superior efficacy in reducing the clinical and motorcomplications associated with long-term levodopa use, as well as in reducing the incidence and severity of adverse effects.

Carbidopa/levodopa

History

Cardiovascular effects of levodopa in aged versus younger patients with Parkinson's disease.

The cardiovascular effects of prolonged administration of levodopa were studied in 54 men and women with Parkinson's disease; 23 of them were younger than 70 and 31 were 70 or older. The patients were evaluated clinically before treatment was started and at regular intervals thereafter. The average optimal dosage of levodopa for both age groups was 3.0 and 2.5 gm per day, respectively, during an average treatment period of 20.7 months. Eleven patients showed hypotension (systolic BP of 105 mm Hg or less) that was not related to dosage; in only 6 did the drug have to be permanently discontinued because of syncope; 3 of this group had an associated psychiatric disorder. Four patients had pretreatment hypertension; in 3 the BP fell to normal during therapy; in the remaining patient the hypertension persisted and was successfully treated by an antihypertensive drug. In 5 patients an occasional atrial or ventricular ectopic beat was noted both before and during levodopa therapy but no therapeutic intervention was required. Thirty of the 46 patients with adequate ECG follow-up did not show any significant changes; 5 others showed an increase, and 11 a decrease in myocardial ischemia. Thus the administration of levodopa in elderly patients with or without heart disease is a relatively safe procedure. The only exception would be patients over 70 years of age with a history of previous myocardial infarction. In this group there seems to be a higher incidence of clinically significant hypotension. In such patients, levodopa therapy should be carried out with great caution.

Befiradol

Befiradol was discovered and developed by Pierre Fabre Médicament, a French pharmaceuticals company. In September 2013, befiradol was out-licensed to Neurolixis, a California-based biotechnology company. Neurolixis announced that it intends to re-purpose befiradol for the treatment of levodopa-induced dyskinesia in Parkinson's disease. In support of this indication, Neurolixis received several research grants from the Michael J. Fox Foundation and preclinical data was published describing the activity of befiradol in animal models of Parkinson's disease. In January 2018, the British charity Parkinson's UK announced that it had awarded Neurolixis a grant to advance development of befiradol up to clinical phase in Parkinson's disease patients. In March 2019, Neurolixis announced that the US Food and Drug Administration (FDA) gave a positive response to Neurolixis' Investigational New Drug (IND) application for NLX-112 to be tested in a Phase 2 clinical study in Parkinson's disease

[Severe parkinsonism due to metoclopramide: the importance of early recognition].

In this article, we present 3 women aged 73, 85 and 88 years who developed metoclopramide-induced parkinsonism. Shortly after starting metoclopramide, bradykinesia and rigidity developed in all 3 patients; tremor and postural instability in 2 of them. We discontinued the metoclopramide after 3-6 months; 2 of the patients had fully recovered 4-6 months later. The 3rd patient died from pneumonia, however, 2 months after discontinuation. Metoclopramide, a dopamine D2-antagonist, is a frequently prescribed anti-emetic drug; however, evidence of its efficacy is limited. In many patients, domperidone, another dopamine D2-antagonist, seems to be a better alternative. Movement disorders due to domperidone are uncommon, presumably because it does not cross the blood-brain barrier. It is likely that metoclopramide-induced parkinsonism is not uncommon; however, it is under-recognized. Risk factors are female sex, advanced age, diabetes mellitus and polypharmacy. Follow-up on patients using metoclopramide is advised.

Vildagliptin

Vildagliptin, sold under the brand name Galvus among others, is an oral anti-hyperglycemic agent (anti-diabetic drug) of the dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1 and GIP by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucagon release by the alpha cells of the islets of Langerhans in the pancreas. Vildagliptin has been shown to reduce hyperglycemia in type 2 diabetes mellitus. Combination with metformin The European Medicines Agency has also approved a combination of vildagliptin and metformin, vildagliptin/metformin (Eucreas by Novartis) as an oral treatment for type-2 diabetes. Adverse effects Adverse effects observed in clinical trials include nausea, hypoglycemia, tremor, headache and dizziness. Rare cases of hepatoxicity have been reported.

Drugs inducing or aggravating parkinsonism: a review.

Drug-induced parkinsonism (DIP) is frequent. The list of drugs able to induce parkinsonism is long and probably incomplete, because new drugs, with previously unknown antidopaminergic activity, are constantly being added. Not all the drugs have the same potency for inducing parkinsonism. We classify these drugs in three groups: (1) drugs with obvious antidopaminergic activity which regularly induce parkinsonism; (2) drugs able to induce parkinsonism in particular individuals and (3) drugs which may aggravate Parkinson's disease treated with levodopa. The reports of isolated cases of parkinsonism induced by widely-used drugs (drugs in group 2) may be the result of either an idiosyncratic side effect or a misdiagnosis of parkinsonism. The antidopaminergic activity of the drugs of this group is weak and not sufficiently demonstrated. Maybe, in these cases, the blockage of other neurotransmitters different from dopamine plays a role in the induction of parkinsonism. Probably, the number of patients with DIP is higher than reported or detected, because many patients suffer from weak symptoms that quickly disappear after drug withdrawal. One of the main points of interest is knowing the list, because all these drugs, specially those of group 1, should be avoided or used with caution in the treatment of some common symptomatic problems in patients with Parkinson's disease, such as depression, arterial hypertension, diabetes mellitus and cardiac disorders. The precautions should extent to other populations especially susceptible to suffer from DIP, such as the elderly or patients with other neurodegenerative disorders, such as Alzheimer's disease.

Substantia nigra

Levodopa The substantia nigra is the target of chemical therapeutics for the treatment of Parkinson's disease. Levodopa (commonly referred to as L-DOPA), the dopamine precursor, is the most commonly prescribed medication for Parkinson's disease, despite controversy concerning the neurotoxicity of dopamine and L-DOPA. The drug is especially effective in treating patients in the early stages of Parkinson's, although it does lose its efficacy over time. Levodopa can cross the blood–brain barrier and increases dopamine levels in the substantia nigra, thus alleviating the symptoms of Parkinson's disease. The drawback of levodopa treatment is that it treats the symptoms of Parkinson's (low dopamine levels), rather than the cause (the death of dopaminergic neurons in the substantia nigra). MPTP

[Movement disorders of drug origin].

The involvement of a drug must be suspected in each patient suffering from a movement disorder. Besides classical neuroleptics used as antipsychotics (butyrophénones, phenothiazines or benzamides), many drugs, mainly "hidden" neuroleptics (prescribed as antinausea, antivomiting, antivertigo, antispasmodic or antihypertensive drugs) or agents prescribed in psychiatric (antidepressants, lithium) or neurological (levodopa in Parkinson's disease, antiepileptics) diseases are known to be able to reveal or produce a movement disorder. Other drug prescribed in internal medicine can also be involved. This review discusses the main characteristics of drug-induced movement disorders as well as their pharmacological approach.

Neurolixis

and Drug Administration (FDA) gave a positive response to Neurolixis' Investigational New Drug (IND) application for befiradol to be tested in a Phase 2 clinical study in Parkinson's disease patients with troublesome Levodopa-induced dyskinesia. Studies published in 2020 using non-human primate models of Parkinson's disease, (MPTP-treated marmosets and MPTP-treated macaques), found that befiradol potently reduced Levodopa-induced dyskinesia at oral doses as low as 0.1 to 0.4 mg/kg.

A brief history of levodopa.

This article highlights some landmarks in the history of levodopa, beginning with its isolation in 1910-13 from seedlings of Vicia faba to the demonstration, in 1961, of its "miraculous" effect in patients with Parkinson's disease (PD). Midway between these two time points, in 1938, L: -dopa decarboxylase was discovered, the enzyme that produces dopamine (DA) from levodopa. In 1957, DA was shown to occur in the brain, and in 1959 it was found to be enriched in the basal ganglia. At that time the striatal localization of DA, together with studies done in 1957-58 in naive and reserpine-treated animals regarding DA in the brain and the central effects of levodopa, suggested its possible involvement in "extrapyramidal control" and "reserpine parkinsonism". Following these discoveries, a study of (postmortem) brains of patients with basal ganglia disorders, including PD, was started, demonstrating, in 1960, a severe striatal DA deficit specifically in PD, thus furnishing a rational basis for the concept of "DA replacement therapy" with levodopa. Accordingly, in 1961, the first highly successful clinical trial with i.v. levodopa was carried out. In 1963, the DA deficit in the PD substantia nigra was found, indicative of a nigrostriatal DA pathway in the human brain, subsequently established in animal studies in 1964-65. In 1967, the chronic, high dose oral levodopa regimen was introduced in treatment of PD. Besides the above highlights in the history of levodopa, the article also cites critical opinions of world authorities in brain research of the time, harmful to the cause of DA, levodopa and PD. Today, the concept of DA replacement with levodopa is uncontested, with levodopa being the "gold standard" of modern drug treatment of PD.

Safinamide

Safinamide (INN; brand name Xadago) is a drug used as an add-on treatment for Parkinson's disease with "off" episodes; it has multiple modes of action, including the inhibition of monoamine oxidase B. It was approved in Europe in February 2015, in the United States in March 2017, and in Canada in January 2019. Medical uses Safinamide is used to treat idiopathic Parkinson's disease as add-on for people taking a stable dose of levodopa (L-dopa) alone or in combination with other Parkinson drugs, to help with "off" episodes when levodopa stops working. Contraindications Safinamide is contraindicated in people with severe liver impairment, with albinism, retinitis pigmentosa, severe diabetic neuropathy, uveitis and other disorders of the retina. Combination with other monoamine oxidase (MAO) inhibitors and pethidine is also contraindicated.

Has drug therapy changed the natural history of Parkinson's disease?

This narrative review examines the effects of drug therapy on the natural history of Parkinson's disease. In terms of modifying the underlying disease process, it is possible that immediate therapy, rather than deferred treatment, can have a positive effect on the underlying disease process. However, it is unlikely that drug therapy has changed mortality from the condition and there is no evidence that it can delay the onset of non-motor features such as dementia and falls. The beneficial effects of drug therapy on the motor symptoms of Parkinson's disease are unquestionable, but these are at the expense of short-term dopaminergic side effects, long-term motor complications, and impulse control disorders. Major questions remain regarding which initial therapeutic approach should be taken which may possibly be answered by the ongoing PD MED trial. The beneficial effects of drug therapy on the motor features of Parkinson's disease have had a fundamental impact on the suffering of patients. The mainstay of these therapies continues to be levodopa, although it is now used at lower doses than in the past and in combination with other drug classes.

Levodopa-induced dyskinesia

In the context of Parkinson's disease (PD), dyskinesia is often the result of long-term dopamine therapy. These motor fluctuations occur in up to 80% of PD patients after 5–10 years of l-DOPA treatment, with the percentage of affected patients increasing over time. Based on the relationship with levodopa dosing, dyskinesia most commonly occurs at the time of peak l-DOPA plasma concentrations and is thus referred to as peak-dose dyskinesia (PDD). As patients advance, they may present with symptoms of diphasic dyskinesia (DD), which occurs when the drug concentration rises or falls. If dyskinesia becomes too severe or impairs the patient's quality of life, a reduction in l-Dopa might be necessary, however this may be accompanied by a worsening of motor performance. Therefore, once established, LID is difficult to treat. Amongst pharmacological treatments, N-methyl-D-aspartate (NMDA) antagonist, (a glutamate receptor), amantadine, has been proven to be clinically effective in a small

The history of parkinsonism: descriptions in ancient Indian medical literature.

The clinical syndrome of parkinsonism was identified in ancient India even before the period of Christ and was treated methodically. The earliest reference to bradykinesia dates to 600 bc. Evidences prove that as early as 300 bc, Charaka proposed a coherent picture of parkinsonism by describing tremor, rigidity, bradykinesia, and gait disturbances as its components. The scenario was further developed by Madhava, Vagbhata, and Dalhana all through history. The 15th-century classic "Bhasava rajyam" introduced the term kampavata, which may be regarded as an ayurvedic analogue of parkinsonism. The pathogenesis of kampavata centered on the concept of imbalance in the vata factor, which controls psychomotor activities. The essential element in therapy was the administration of powdered seed of Mucuna pruriens, or atmagupta, which as per reports, contains 4%-6% of levodopa. In addition to proving the existence and identification of parkinsonism in ancient India, the study points to the significance of ancient Indian Sanskrit works in medical history.

Multiple system atrophy

Drug therapy Levodopa (L-Dopa), a drug used in the treatment of Parkinson's disease, improves parkinsonian symptoms in a small percentage of MSA patients. A recent trial reported that only 1.5% of MSA patients experienced any improvement at all when taking levodopa, their improvement was less than 50%, and even that improvement was a transient effect lasting less than one year. Poor response to L-Dopa has been suggested as a possible element in the differential diagnosis of MSA from Parkinson's disease. The drug riluzole is ineffective in treating MSA or PSP. Rehabilitation Management by rehabilitation professionals including physiatrists, physiotherapists, occupational therapists, speech therapists, and others for difficulties with walking/movement, daily tasks, and speech problems is essential.

Juvenile Parkinsonism: clinical and metabolic characteristics.

Twenty one patients with idiopathic Parkinsonism beginning before the age of 40 years were investigated. The mean duration of the disease was 19 years. There was a good and sustained response to levodopa. Only four patients reached stages IV and V (Hoehn and Yahr). Intolerance to levodopa was observed in the more advanced stages of the disease. In the series the familial incidence of Parkinsonism (2 cases) and essential tremor (3 cases) was very low. Thyroid disorder, diabetes mellitus or macrocytic anaemia was not found in any of the cases.

Which drugs cause treatment-related problems? Analysis of 10,672 problems within the outpatient setting.

Treatment-related problems (TRPs) may pose risks for patients if unaddressed. With the increased complexity of health care, it is important to target pharmacists' efforts to patients that are at high risk for TRPs. The present study aimed to identify medications most commonly associated with TRPs. Outpatient departments of five public and teaching hospitals in Jordan. TRPs and drugs most commonly implicated with TRPs were assessed for patients recruited from outpatient clinics in five major hospitals in Jordan using a standardized and validated pharmaceutical care manual. Drugs associated with different types of TRPs. Ultimately, 2,747 patients, with a total of 10,672 TRPs, were included in the study. The medication groups most commonly associated with TRPs were cardiovascular (53.0%), endocrine (18.1%), and gastrointestinal (7.7%) drugs. The most common specific drugs associated with TRPs from any category were atorvastatin (12.5%), metformin (8.5%), simvastatin (6.2%), and enalapril (5.9%). Cardiovascular medications were the most common drugs implicated with multiple subtypes of TRPs - most commonly, allergic reaction or undesirable effect (88.5%), drug product not available (87.3%), safety interaction issues (81.8%), a need for additional or more frequent monitoring (78.0%), and more effective drugs available (77.2%). Hypertension, diabetes mellitus, and dyslipidemia were the most common diseases associated with different subtypes of TRPs. The present study identified high-risk drugs for TRPs, which can be used as identification of targeting approach TRPs. Such an approach would improve care provided to patients and can inform health care policies.

Gout and Levodopa: An unknown adverse effect?

We report the case of a 77-year-old man with Parkinson's disease (PD) who experimented for the first time gout crisis after the initiation of levodopa. Levodopa was withdrawn, and colchicine and allopurinol were initiated to treat the gout crisis. Because of PD progression, levodopa was reintroduced, and the patient presented relapse of gout flare. To further explore the association between gout and levodopa, we extracted and synthetized all Individual Case Safety Reports of gout associated with levodopa in the World Health Organization pharmacovigilance database, VigiBase<sup®</sup , up to April 2021. 43 cases of gout were reported in VigiBase<sup®</sup with drugs from N04BA ATC class. Levodopa was suspected in fifteen cases among which improvement was noticed in six cases (two after levodopa withdrawal, two despite treatment continuation, and two cases lacking details about action taken with levodopa); three cases did not recover; in the remaining six cases, evolution was not known. "Hyperuricemia" was not mentioned in the Summary of Product Characteristics of medicine containing levodopa; however, "abnormality biologics test with uric acid" was mentioned. Despite few cases of recovery after reduced doses of levodopa, the above-described case of positive reintroduction was an argument in favor of the role of levodopa in gout flare. This study highlights a potential association between levodopa and gout through an analysis of the cases reported in the WHO pharmacovigilance database.