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Extended-spectrum-␤-lactamase (ESBL)-producing pathogens are associated with extensive morbidity and mortality and rising health care costs. Scant data exist on the impact of antimicrobial therapy on clinical outcomes in patients with ESBL bloodstream infections (BSI), and no large studies have examined the impact of cefepime therapy. A retrospective 3-year study was performed at the Detroit Medical Center on adult patients with BSI due to ESBL-producing Klebsiella pneumoniae or Escherichia coli. Data were collected from the medical records of study patients at five hospitals between January 2005 and December 2007. Multivariate analysis was performed using logistic regression. One hundred forty-five patients with BSI due to ESBL-producing pathogens, including K. pneumoniae (83%) and E. coli (16.5%), were studied. The mean age of the patients was 66 years. Fifty-one percent of the patients were female, and 79.3% were African-American. Fifty-three patients (37%) died in the hospital, and 92 survived to discharge. In bivariate analysis, the variables associated with mortality (P < 0.05) were presence of a rapidly fatal condition at the time of admission, use of gentamicin as a consolidative therapeutic agent, and presence of one or more of the following prior to culture date: mechanical ventilation, stay in the intensive care unit (ICU), and presence of a central venous catheter. In multivariate analysis, the predictors of in-hospital mortality included stay in the intensive care unit (odds ratio When added to the model, receipt of empirical cefepime alone (n ‫؍‬ 43) was associated with increased mortality, although this association did not reach statistical significance (OR, 1.66; 95% CI, 0.71 to 3.87). The median length of hospital stay was shorter for patients receiving empirical cefepime than for those receiving empirical or consolidated carbapenem therapy. In multivariate analysis, empirical therapy with cefepime for BSI due to an ESBL-producing pathogen was associated with a trend toward an increased mortality risk and empirical carbapenem therapy was associated with a trend toward decreased mortality risk.[

Rapid identification of patients who are colonized with carbapenemase-producing organisms (CPO) is included in multiple national guidelines for containment of these organisms. In a multisite study, we evaluated the performance of the Cepheid Xpert Carba-R assay, a qualitative diagnostic test that was designed for the rapid detection and differentiation of the blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP-1 genes from rectal swab specimens. A double rectal swab set was collected from 383 patients admitted at four institutions (2 in the United States, 1 in the United Kingdom, 1 in Spain). One swab was used for reference culture (MacConkey broth containing 1 mg/liter of meropenem and subcultured to a MacConkey agar plate with a 10-μg meropenem disk) and for sequencing of DNA obtained from carbapenem-nonsusceptible isolates for carbapenemase identification. The other swab was used for the Xpert Carba-R assay. In addition to the clinical rectal swabs, 250 contrived specimens (108 well-characterized CPO and 142 negative controls spiked onto negative rectal swabs) were tested. Overall, 149/633 (23.5%) samples were positive by the Xpert Carba-R assay. In 6 samples, multiple targets were detected (4 VIM/OXA-48, 1 IMP-1/NDM, and 1 NDM/KPC). The Xpert Carba-R assay detected 155 targets (26 IMP-1, 30 VIM, 27 NDM, 33 KPC, 39 OXA-48) within a time range of 32 to 48 min. The sensitivity, specificity, and positive and negative predictive values of the Xpert Carba-R assay compared to those of the reference culture and sequencing results were 96.6% (95% confidence interval [CI], 92.2% to 98.9%), 98.6% (95% CI, 97.1% to 99.4%), 95.3%, and 99.0%, respectively. The Cepheid Xpert Carba-R assay is an accurate and rapid test to identify rectal colonization with CPO, which can guide infection control programs to limit the spread of these organisms.

IntroductionMeningitis is one of the leading causes of death among patients living with HIV in sub-Saharan Africa. There is no widespread tracking of the incidence rates of causative agents among patients living with HIV, yet the aetiologies of meningitis are different than those of the general population.MethodsWe reviewed the scientific literature published in PubMed to determine the incidence rates of meningitis among hospitalized people living with HIV in sub-Saharan Africa and report our findings from seven studies across sub-Saharan Africa.ResultsWe found high rates of cryptococcal meningitis (19–68%). Tuberculous meningitis was lower (1–36%), although some centres included possible cases as “other” meningitis; therefore, this may not be a true representation of the total cases. Pyogenic meningitis ranged from 6 to 30% and “other” meningitis ranged from 7 to 28% of all reported cases of meningitis. Mortality rates ranged from 25 to 68%. This review describes the most common aetiologies and provides practical diagnostic, treatment and prevention considerations as they apply to the individual living with HIV in sub-Saharan Africa.ConclusionsDiagnosis is often limited, and wider availability of accurate and low-cost laboratory diagnostics is desperately needed for prompt diagnosis and initiation of appropriate treatment. Wider acceptance and adoption of available preventative modalities can decrease the incidence of potentially fatal central nervous system infections in African patients living with HIV.

Geotrichum candidum is a saprophytic yeast known to colonize the human skin, respiratory tract and gastrointestinal tract. It can cause local or disseminated disease (geotrichosis), mainly in the immunocompromised host. Trauma, indwelling catheter use, prolonged broad-spectrum antibiotic treatment and critical illness have also been implicated as risk factors. Here we report the first case, to our knowledge, of cutaneous G. candidum infection in a burn patient. The isolate had a high amphotericin B minimum inhibitory concentration (MIC) and the patient experienced concomitant Candida orthopsilosis fungaemia, and so was treated with a combination of voriconazole and micafungin. This case highlights the importance of source control, rapid identification of G. candidum infection and MIC determination to guide antifungal therapy, which typically consists of amphotericin B with or without flucytosine or voriconazole alone. Clinicians should be aware of geotrichosis as a clinical entity in burn patients as well as in the immunocompromised. Antifungal resistance and breakthrough disease are an ongoing concern due to the increasing number of immunocompromised at-risk patients and the use of routine mould prophylaxis.

Antimicrobial susceptibility results from broth microdilution MIC testing of 993 Staphylococcus lugdunensis isolates recovered from patients at a tertiary care medical center from 2008 to 2015 were reviewed. Ninety-two oxacillin-susceptible isolates were selected to assess the accuracy of penicillin MIC testing, the penicillin disk diffusion test, and three ␤-lactamase tests, including the cefoxitin-induced nitrocefin test, penicillin cloverleaf assay, and penicillin disk zone edge test. The results of all phenotypic tests were compared to the results of blaZ PCR. The medical records of 62 patients from whom S. lugdunensis was isolated, including 31 penicillinsusceptible and 31 penicillin-resistant strains, were retrospectively reviewed to evaluate the clinical significance of S. lugdunensis isolation, the antimicrobial agents prescribed, if any, and the clinical outcome. MIC testing revealed that 517/993 (52.1%) isolates were susceptible to penicillin and 946/993 (95.3%) were susceptible to oxacillin. The induced nitrocefin test was 100% sensitive and specific for the detection of ␤-lactamase compared to the blaZ PCR results, whereas the penicillin disk zone edge and cloverleaf tests showed sensitivities of 100% but specificities of only 9.1% and 89.1%, respectively. The penicillin MIC test had 100% categorical agreement with blaZ PCR, while penicillin disk diffusion yielded one major error. Only 3/31 patients with penicillin-susceptible isolates were treated with a penicillin family antimicrobial. The majority of cases were treated with other ␤-lactams, trimethoprimsulfamethoxazole, or vancomycin. These data indicate that nearly all isolates of S. lugdunensis are susceptible to narrow-spectrum antimicrobial agents. Clinical laboratories in areas with resistance levels similar to those described here can help promote the use of these agents versus vancomycin by effectively designing their antimicrobial susceptibility reports to convey this message.KEYWORDS Staphylococcus, antimicrobial resistance, beta-lactams, lugdunensis S taphylococcus spp. are normal skin flora inhabitants and, in some cases, opportunistic human pathogens (1). The coagulase-negative staphylococci (CoNS) are typically less virulent than Staphylococcus aureus in healthy human hosts. One exception is Staphylococcus lugdunensis, which may exhibit increased virulence compared to that of other CoNS (2). Infections associated with S. lugdunensis can include skin and soft tissue infections, native valve endocarditis, urinary tract infections, and prosthetic device infections (2).Isolates of CoNS, in particular Staphylococcus epidermidis, that harbor the mecA gene can have oxacillin MICs in the 0.5-to 2.0-g/ml range, which is much lower than the oxacillin MICs observed in mecA-positive isolates of S. lugdunensis and S. aureus (3-7). As such, the Clinical and Laboratory Standards Institute (CLSI) recommends that

Background: The World Health Organization (WHO) recommends screening patients living with AIDS to detect and treat early cryptococcal infection. Methods: The authors evaluated a cryptococcal antigen (CrAg) screening and treatment program at an HIV/AIDS clinic in Malawi. Eligible patients were of age >18 years, had a CD4 count <100 cells/mL or WHO clinical HIV/AIDS stage III or IV. Results: Of 552 patients who presented for care, 113 were eligible, and all (100%) agreed to CrAg screening. Of them, 2 (1.8%; 95% confidence interval [CI]: 0-4.2%) patients were CrAg positive. Among those with CD4 count <100 cells/mL or WHO stage IV, the CrAg prevalence was 3.5% (95% CI: 0-8.4%) and 5.0% (95% CI: 0-15%), respectively. Conclusion: A CrAg screening program was acceptable to new patients in a Malawian HIV/AIDS clinic. The CrAg prevalence for patients with CD4 count < 100 cells/mL and WHO stage IV was consistent with cost-effectiveness estimates. CrAg screening and treatment programs for patients living with AIDS should be expanded.

A case of cryptogenic brain abscess caused by Gemella morbillorum is reported in a 28-year-old immunocompetent man who presented with seizures and hemiparesis. The patient underwent successful stereotactic drainage of the abscess with complete resolution of symptoms and radiographic evidence of resolution. We report the significant pathogenic potential of a normal commensal rarely identified in neurologic infections.