Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study.

BACKGROUND: Bloodstream infections (BSI) caused by Enterobacteriaceae show increasing frequency of resistance to third-generation cephalosporin (3GC) antibiotics on the African continent but the mortality impact has not been quantified. METHODS: We used historic data from six African hospitals to assess the impact of 3GC resistance on clinical outcomes in Escherichia coli and Klebsiella pneumoniae BSI. We matched each bacteraemic patient to two uninfected patients. We compared outcomes between 3GC-susceptible and 3GC-resistant BSI and their respective uninfected controls using Cox regression models. RESULTS: For 1431 E. coli BSI patients, we matched 1152 (81%) 3GC-susceptible and 279 (19%) 3GC-resistant cases to 2263 and 546 uninfected inpatient controls. For 1368 K. pneumoniae BSI patients, we matched 502 (37%) 3GC-susceptible and 866 (63%) 3GC-resistant cases to 982 and 1656 uninfected inpatient controls. We found that 3GC-resistant E. coli had similar hazard ratios (HRs) for in-hospital mortality over their matched controls as compared to susceptible infections over their controls (ratio of HRs 1.03, 95% CI 0.73-1.46). Similarly, 3GC-resistance in K. pneumoniae BSI was not associated with mortality (ratio of HR 1.10, 95% CI 0.80-1.52). Estimates of mortality impact varied by site without a consistent pattern. CONCLUSIONS: In a retrospective analysis, including the use of matched uninfected patients, there did not appear to be an impact of 3GC-resistance on mortality in E. coli or K. pneumoniae BSI in African hospitals, as compared with susceptible BSI with equivalent species. Better information on the actual use of antibiotics in treating infections in African hospitals would improve these impact estimates.

Erratum to: Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study.

[This corrects the article DOI: 10.1093/jacamr/dlaa130.].

Presentation and outcome of suspected sepsis in a high-HIV burden, high antiretroviral coverage setting.

OBJECTIVE: To define sepsis syndromes in high-HIV burden settings in the antiretroviral therapy (ART) era. METHODS: We characterized a prospective cohort of adults presenting to a tertiary emergency department in Harare, Zimbabwe with suspected community-acquired sepsis using blood and urine cultures, urine tuberculosis lipoarabinomannan (TB LAM), and serum cryptococcal antigen (CrAg) testing. The primary outcome was 30-day all-cause mortality. RESULTS: Of 142 patients enrolled 68% (n=96/142, 95% confidence interval (CI) [60-75%]) were HIV-positive, 41% (n=39/96, 95% CI [31-50%]) of whom were ART-naïve. Among HIV-positive patients, both opportunistic pathogens (TB LAM-positivity, 36%, 95% CI [24-48%]; CrAg-positivity, 15%, 95% CI [7-23%]) and severe non-AIDS infections (S. pneumoniae urine antigen-positivity 12%, 95% CI [4-20%]; bacteraemia 17% (n=16/96, 95% CI [9-24%]), of which 56% (n=9/16, 95% CI [30-80%]) were gram-negative organisms) were common. Klebsiella pneumoniae recovered from blood and urine was uniformly resistant to ceftriaxone, as were most Escherichia coli isolates. Acknowledging the power limitations of our study, we conclude that relative to HIV-negative patients, HIV-positive patients had modestly higher 30-day mortality (adjusted hazard ratio (HR) 1.88, 95% CI [0.78-4.55]; p=0.16, and 3.59, 95% CI [1.27-10.16], p=0.02) among those with and without viral suppression, respectively. CONCLUSION: Rapid point-of-care assays provide substantial clinically actionable information in the setting of suspected sepsis, even in areas with high ART coverage. Antimicrobial resistance to first-line antibiotics in high burden settings is a growing threat.

Effect of handrubbing using locally-manufactured alcohol-based handrubs in paediatric wards in Harare, Zimbabwe.

We assessed bacterial contamination of hands of adults present in paediatric wards in two tertiary-care hospitals in Harare, Zimbabwe and the microbiologic efficacy of locally-manufactured alcohol-based hand rub (ABHR). During unannounced visits, samples were collected using hand-print and hand-rinse methods. Samples were collected from 152 individuals (16 nurses, 10 doctors, 28 students, 86 parents/guardians, 12 others). Contamination of hands with Gram-negative bacteria was found in 91% of adults tested with a mean of 14.6 CFU (hand-rinse method; IQR 3-65), representing a high risk for transmission of pathogens potentially leading to nosocomial infections. A single application of ABHR under controlled conditions achieved an average of 82% (or 0.72 log) reduction in detectable counts. Amongst 49 Enterobacteriaceae isolates from hands, 53% were resistant to gentamicin and 63% were resistant to cefpodoxime. Use of ABHR represents an attractive intervention for reducing nosocomial infections in this setting.

Carriage of antibiotic-resistant Enterobacteriaceae in hospitalised children in tertiary hospitals in Harare, Zimbabwe.

BACKGROUND: Extended-spectrum ß-lactamase-producing and gentamicin resistant Enterobacteriaceae are increasingly recognised as a major cause of infection in low-income countries. We assessed the prevalence of gastrointestinal carriage of these bacteria in hospitalised children in Harare, Zimbabwe. METHODS: We conducted a cohort study in paediatric inpatients at two tertiary-referral hospitals between May and July 2015. Rectal swabs and faecal samples were collected within 24 h of admission and further follow-up samples were collected on alternate days during hospitalization. Disc-based, selective and enrichment methods were used to detect carriage of these two forms of resistance. Standard methods were used to confirm resistance status and determine the susceptibility of resistant isolates to other commonly-used antibiotics. RESULTS: One hundred and sixty four paediatric inpatient admissions (median age = 1.0 year, IQR = 0.2-2.2years) were enrolled, and an average of 1.9 faecal samples per patient were collected. On admission, 68/164 (41%) patients had both ESBL and gentamicin-resistant Enterobacteriaceae detected, 18 (11%) had ESBL only, 17 (10%) had gentamicin resistance only and 61 (37%) had negative screening for both forms of resistance. During hospitalisation, 32/164 (20%) patients were found to have a type of resistant organism which was not present in their admission sample. We found that faecal samples and use of a selective enrichment broth enhanced the detection of resistant organisms. Amongst resistant bacteria isolated, there were high levels of resistance to ciprofloxacin and chloramphenicol, but not ertapenem. CONCLUSIONS: More than half of children had enteric carriage of a clinically-relevant form of antibiotic resistance on admission to public-sector hospitals in urban Zimbabwe. Additionally, a fifth of children acquired a further form of resistance during hospitalisation. Urgent action is needed to tackle the spread of antibiotic resistant enteric bacteria in African hospitals.

Molecular Identification of Mycobacterium Species of Public Health Importance in Cattle in Zimbabwe by 16S rRNA Gene Sequencing.

Mycobacterium species are naturally found in the environment as well as in domestic animals such as cattle. So far, more than 150 species of Mycobacterium, some of which are pathogenic, have been identified. Laboratory isolation, detection and identification of Mycobacterium species are therefore critical if human and animal infections are to be controlled. The objective of this study was to identify Mycobacterium species isolated in cattle in Zimbabwe using 16S ribosomal RNA gene amplification and sequencing. A total of 134 cow dung samples were collected throughout Zimbabwe and mycobacteria were isolated by culture. Only 49 culture isolates that were found to be acid-fast bacilli positive by Ziehl-Neelsen staining. The 16S rRNA gene was successfully amplified by PCR in 41 (84%) of the samples. There was no amplification in 8 (16%) of the samples. Out of the 41 samples that showed amplification, 26 (63%) had strong PCR bands and were selected for DNA sequencing. Analysis of the DNA sequences showed that 7 (27%) belonged to Mycobacterium neoaurum, 6 (23%) belonged to Mycobacterium fortuitum, 3 (12%) to Mycobacterium goodii, 2 (1%) to Mycobacterium arupense, 2 (1%) to Mycobacterium peregrinum or M. septicum and 1 isolate (0.04%) to Mycobacterium elephantis. There were 5 (19%) isolates that were non-mycobacteria and identified as Gordonia terrae, a close relative of Mycobacterium. The study therefore provided a molecular basis for detection and identification of Mycobacterium species in animals and humans.