Population pharmacokinetics and dosing simulations of amoxicillin in obese adults receiving co-amoxiclav.

BACKGROUND: Pneumonia, skin and soft tissue infections are more frequent in obese patients and are most often treated by co-amoxiclav, using similar dosing regimens to those used for non-obese subjects. No data are available on amoxicillin pharmacokinetics among obese subjects receiving co-amoxiclav. MATERIALS AND METHODS: Prospective, single-centre, open-label, non-randomized, crossover pharmacokinetic trial having enrolled obese otherwise healthy adult subjects. A first dose of co-amoxiclav (amoxicillin/clavulanate 1000/200 mg) was infused IV over 30 min, followed by a second dose (1000/125 mg) administered orally, separated by a washout period of ≥24 h. We assayed concentrations of amoxicillin by a validated ultra HPLC-tandem MS technique. We estimated population pharmacokinetic parameters of amoxicillin by non-linear mixed-effect modelling using the SAEM algorithm developed by Monolix. RESULTS: Twenty-seven subjects were included in the IV study, with 24 included in the oral part of the study. Median body weight and BMI were 109.3 kg and 40.6 kg/m2, respectively. Amoxicillin pharmacokinetics were best described by a two-compartment model with first-order elimination. Mean values for clearance, central volume, intercompartmental clearance and peripheral volume were, respectively, 14.6 L/h, 9.0 L, 4.2 L/h and 6.4 L for amoxicillin. Oral bioavailability of amoxicillin was 79.7%. Amoxicillin Cmax after oral administration significantly reduced with weight (P = 0.013). Dosing simulations for amoxicillin predicted that most of the population will achieve the pharmacodynamic target of fT>MIC ≥40% with the regimen of co-amoxiclav 1000/200 mg (IV) or 1000/125 mg (oral) q8h for MICs titrated up to 0.5 mg/L (IV) and 1 mg/L (oral). CONCLUSIONS: Pharmacokinetic/pharmacodynamic goals for amoxicillin can be obtained in obese subjects.

Emergence of echinocandin-resistant Candida spp. in a hospital setting: a consequence of 10 years of increasing use of antifungal therapy?

Since their introduction in the 2000s, echinocandin drugs have become widely used for the treatment and prophylaxis of invasive fungal infections and, notably, invasive candidiasis. Although cases of breakthrough candidiasis in patients receiving echinocandins have been reported, clinical failure during echinocandin treatment due to the acquisition of resistance by a normally susceptible Candida spp. isolate is considered rare. To date, no publications have been published correlating the use of echinocandins and the emergence of echinocandin resistance among Candida species. So, our goal is to report an initial analysis of echinocandin use in relation to the emergence of resistant Candida isolates. We report here a single-centre experience of the emergence of eight resistant isolates belonging to normally susceptible Candida species in six patients receiving echinocandins. We describe the context and analyse the use of echinocandins over the previous decade. For seven of these isolates, we identified FKS gene mutations involved in decreased susceptibility. Seven isolates were obtained in 2011, on the heels of a ten-fold increase in caspofungin use over the preceding decade. In contrast, in 2012, the use of echinocandins decreased in our institution by 19.5 % and, in that year, only one Candida-resistant isolate was detected, despite the stable global epidemiology of invasive candidaemia. This work underlines the necessity of improving the prescription of antifungal drugs. Improvement in the monitoring of strain susceptibility should also be considered in order to better detect the emergence of resistant or non-susceptible yeast strains.

Non-typhi Salmonella enterica urinary tract infections.

OBJECTIVE: Non-typhi Salmonella enterica urinary tract infections (UTIs) are not frequent and rarely reported in the literature. We aimed to characterize clinical presentations and risk factors for the infection. PATIENTS AND METHODS: We performed a retrospective study of non-typhi Salmonella enterica strains isolated from urine cytobacteriological examinations (UCBE) collected between January 1, 1996 and October 30, 2014 and analyzed by the microbiology laboratories of the university hospitals of the western part of Île-de-France and of Paris, France. RESULTS: Twenty UCBEs positive for non-typhi Salmonella enterica were analyzed. The sex ratio was 0.53 and the average age of patients was 57 years. Clinical presentations were acute pyelonephritis, acute cystitis, and prostatitis. Eight cases of bacteremia were identified. Diarrhea was observed in half of patients, either before the UTI or simultaneously. No patient required to be transferred to the intensive care unit. Immunodeficiency and/or diabetes were observed in eight patients. Three patients presented with a uropathy. Prescribed antibiotics were third generation cephalosporins and fluoroquinolones. The average treatment duration was 20 days. A spondylitis and a purulent pleurisy were observed and deemed related to the UTI. Patient outcome was always favorable following treatment prescription. CONCLUSION: Non-typhi Salmonella enterica UTIs are rare. They are mainly observed in elderly patients presenting with immunodeficiency or an underlying urological disorder.

Adenovirus related lymphohistiocytic hemophagocytosis: Case report and literature review.

INTRODUCTION: Adenoviral infection is a classic cause of lymphohistiocytic hemophagocytosis (LH) in bone marrow transplantation but is rare outside this setting. CASE REPORT: A 31-year-old female, with a history of treated mesencephalic astrocytoma, was hospitalized for fever, pancytopenia, elevated liver enzymes, hyperferritinemia and hypertriglyceridemia. Adenovirus viral load in blood was 7.3×10(9) copies/mL. Bone marrow aspirate examination confirmed LH. The patient recovered without specific LH or adenovirus-directed treatment. CONCLUSION: Adenovirus-related LH, common in bone marrow transplant recipients, should also be considered in patients with chemotherapy in solid tumors.

Chronic gonococcal arthritis with C5 deficiency presenting with brief flare-ups: case study and literature review.

Gonococcal arthritis is typically acute and appears within 3 weeks after initial infection. Chronic gonococcal arthritis is now exceptionally rare, since the advent of the antibiotic era. Numerous host factors are involved in gonococcal dissemination, such as complement deficiency, HIV and gonococcus strain characteristics. Gonococcal arthritis shares the same risk factors. In this instance, our patient was a 16-year-old girl suffering from persistent polyarthralgia with joint swelling presenting with brief flare-ups for a period of 1 year. She disclosed a single episode of unprotected sexual intercourse 1 year ago, i.e. just before developing her first rheumatological symptoms. Therefore, we performed a joint aspiration (arthrocentesis), and synovial fluid was inoculated directly into aerobic and anaerobic blood culture bottles, which tested positive for Neisseria gonorrhoeae within 24 h. Clinical presentation was consistent with previous reports of chronic gonococcal arthritis. Further investigation revealed a C5 complement deficiency, which might explain the chronic Neisseria process. A favourable outcome was reached after a ten-day course of IV ceftriaxone, with no apparent sequelae found during follow-up 6 weeks later. This case demonstrates an unusual gonococcal arthritis with brief flare-ups for the course of a year, followed by a subacute form. N. meningitidis infections, similar to N. gonorrhoeae, are typically acute and may sometimes be involved in chronic processes. However, this characteristic appears to be rare in the case of N. gonorrhoeae. Risk factors for this chronic process will be discussed with a review of the literature.

An overview of acute otitis media in Australian Aboriginal children living in remote communities.

Australian Aboriginal children experience early, persistent and severe middle ear infections. We conducted a review of the medical literature that addressed acute otitis media (AOM) in Australian Aboriginal children. Comparisons were made with the recent guidelines on the diagnosis and management of AOM prepared by the American Academies of Pediatrics and Family Physicians (AAP & AAFP 2004). Otitis media in Aboriginal children living in remote communities begins in the first 3 months of life following early bacterial colonisation. Young children with persistent signs of suppurative disease (bulging of the tympanic membrane or middle ear discharge) are probably most at risk of developing chronic suppurative otitis media.

Molecular characterisation of pneumococcal serotype 16F: Established predominant carriage and otitis media serotype in the 7vPCV era.

Young Australian Aboriginal children in remote communities experience very high rates of pneumococcal carriage and otitis media. Prior to introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV, Prevenar), serotype 16F was an important type found in nasal and ear discharge swabs. Since commencement of pneumococcal immunisation for Aboriginal infants in 2001, 16F has become the predominant established serotype in carriage and otitis media in young Aboriginal children. BOX typing and multi-locus sequence typing revealed a diverse population of serotype 16F strains, and evidence of potential capsule switching from a vaccine serotype 4 to a serotype 16F.

Bats, cats, and rabies in an urban community.

Bats are the primary vectors of rabies in humans in the United States. In the urban environment they generally are found within buildings where they may bite people or be attacked by cats or dogs. Given the high probability that any bat that bites a person may be rabid, antirabies prophylaxis should be administered as soon as possible after the incident. This should not be delayed pending laboratory results on the bat. Children should be taught to avoid contact with moribund bats. Cats are more likely to be involved with rabid bats than dogs, but they are less likely to be vaccinated against rabies. The occasional rabid cat in an urban community may have acquired its infection from a bat. Therefore, it is vital that communities enforce rabies vaccination for cats as well as dogs.