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Background Tobramycin is a critical cystic fibrosis treatment however it causes ototoxicity. This study tested D-methionine protection from tobramycin-induced ototoxicity and potential antimicrobial interference. Methods Auditory brainstem responses (ABR) and outer hair cell (OHC) quantifications measured protection in guinea pigs treated with tobramycin and a range of D-methionine doses. In vitro antimicrobial interference studies tested inhibition and post antibiotic effect assays. In vivo antimicrobial interference studies tested normal and neutropenic E. coli murine survival and intraperitoneal lavage bacterial counts. Results D-methionine conferred significant ABR threshold shift reductions. OHC protection was less robust but significant at 20 kHz in the 420 mg/kg/day group. In vitro studies did not detect D-methionine-induced antimicrobial interference. In vivo studies did not detect D-methionine-induced interference in normal or neutropenic mice. Conclusions D-methionine protects from tobramycin-induced ototoxicity without antimicrobial interference. The study results suggest D-met as a potential otoprotectant from clinical tobramycin use in cystic fibrosis patients.

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Background-The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain.Methods-We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group).Results-In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001).Conclusions-The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.

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Background: The extent of extended spectrum beta lactamase (ESBL) producing clinical isolates is now a global concern. The prevalence of ESBLs varies between species, geographically and with time. Delays in commencing appropriate therapy have been shown to have an impact on morbidity, mortality and hospital associated costs. The availability of current South African data will provide the evidence required to implement appropriate health measures.Methods: A retrospective descriptive study was performed for the period from May 2008 to April 2009. Consecutive clinical specimens were obtained from admitted patients and patients referred from primary health care clinics to Dr. George Mukhari tertiary hospital in Pretoria, South Africa. Isolates from blood, cerebrospinal fluid, urine, sputum, pus and stools were processed using conventional laboratory methods. Isolates were identified and susceptibility testing done on the Microscan® using the CLSI guidelines.Demographic, clinical and laboratory data were evaluated.Results: ESBL production was identified in 454 (18%) of the enterobacteriaceae isolated this period. The clinical source was predominantly non-sterile sites, 386 (83%) compared to 78 (17%) from sterile sites. The majority of isolates were from pus swabs (170) 44%, while 134 (35%) were from urine. Of the isolates identified, 271 (29%) were Klebsiella pneumoniae, 89 (9%) Escherichia coli, 25 (3%) Proteus mirabilis, 25 (5%) Enterobacter cloacae, 12 (1%) Klebsiella oxytoca and the rest Enterobacter aerogenes, Morganella morganii, Proteus vulgaris, Citrobacter freundii and Serratia marcescens. The prevalence of ESBLs in the Klebsiella pneumoniae isolates was found to be 271 (46%) and that for Escherichia coli 89 (12%).Conclusion: At our institution, the overall prevalence of ESBL producing enterobacteriaceae of 18%, reaffirms the global spread of ESBL producing bacteria. The presence of ESBLs in most of the common enterobacteriacea is consistent with the horizontal spread of ESBL genetic material. Due to the significant epidemiological implications; detection and surveillance would benefit health interventions at our institution and the country.

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