Burden of bacterial antimicrobial resistance in low-income and middle-income countries avertible by existing interventions: an evidence review and modelling analysis.

National action plans enumerate many interventions as potential strategies to reduce the burden of bacterial antimicrobial resistance (AMR). However, knowledge of the benefits achievable by specific approaches is needed to inform policy making, especially in low-income and middle-income countries (LMICs) with substantial AMR burden and low health-care system capacity. In a modelling analysis, we estimated that improving infection prevention and control programmes in LMIC health-care settings could prevent at least 337 000 (95% CI 250 200-465 200) AMR-associated deaths annually. Ensuring universal access to high-quality water, sanitation, and hygiene services would prevent 247 800 (160 000-337 800) AMR-associated deaths and paediatric vaccines 181 500 (153 400-206 800) AMR-associated deaths, from both direct prevention of resistant infections and reductions in antibiotic consumption. These estimates translate to prevention of 7·8% (5·6-11·0) of all AMR-associated mortality in LMICs by infection prevention and control, 5·7% (3·7-8·0) by water, sanitation, and hygiene, and 4·2% (3·4-5·1) by vaccination interventions. Despite the continuing need for research and innovation to overcome limitations of existing approaches, our findings indicate that reducing global AMR burden by 10% by the year 2030 is achievable with existing interventions. Our results should guide investments in public health interventions with the greatest potential to reduce AMR burden.

Innovation for infection prevention and control-revisiting Pasteur's vision.

Louis Pasteur has long been heralded as one of the fathers of microbiology and immunology. Less known is Pasteur's vision on infection prevention and control (IPC) that drove current infection control, public health, and much of modern medicine and surgery. In this Review, we revisited Pasteur's pioneering works to assess progress and challenges in the process and technological innovation of IPC. We focused on Pasteur's far-sighted conceptualisation of the hospital as a reservoir of microorganisms and amplifier of transmission, aseptic technique in surgery, public health education, interdisciplinary working, and the protection of health services and patients. Examples from across the globe help inform future thinking for IPC innovation, adoption, scale up and sustained use.

Characterisation of Staphylococci species from neonatal blood cultures in low- and middle-income countries.

BACKGROUND: In low- and middle-income countries (LMIC) Staphylococcus aureus is regarded as one of the leading bacterial causes of neonatal sepsis, however there is limited knowledge on the species diversity and antimicrobial resistance caused by Gram-positive bacteria (GPB). METHODS: We characterised GPB isolates from neonatal blood cultures from LMICs in Africa (Ethiopia, Nigeria, Rwanda, and South Africa) and South-Asia (Bangladesh and Pakistan) between 2015-2017. We determined minimum inhibitory concentrations and performed whole genome sequencing (WGS) on Staphylococci isolates recovered and clinical data collected related to the onset of sepsis and the outcome of the neonate up to 60 days of age. RESULTS: From the isolates recovered from blood cultures, Staphylococci species were most frequently identified. Out of 100 S. aureus isolates sequenced, 18 different sequence types (ST) were found which unveiled two small epidemiological clusters caused by methicillin resistant S. aureus (MRSA) in Pakistan (ST8) and South Africa (ST5), both with high mortality (n = 6/17). One-third of S. aureus was MRSA, with methicillin resistance also detected in Staphylococcus epidermidis, Staphylococcus haemolyticus and Mammaliicoccus sciuri. Through additional WGS analysis we report a cluster of M. sciuri in Pakistan identified between July-November 2017. CONCLUSIONS: In total we identified 14 different GPB bacterial species, however Staphylococci was dominant. These findings highlight the need of a prospective genomic epidemiology study to comprehensively assess the true burden of GPB neonatal sepsis focusing specifically on mechanisms of resistance and virulence across species and in relation to neonatal outcome.

Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications.

BACKGROUND: Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). METHODS: We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. RESULTS: Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. CONCLUSIONS: In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.

Antibiotic use in pregnancy: knowledge, attitudes and practices among pregnant women in Cape Town, South Africa.

OBJECTIVES: To establish the knowledge, attitudes and practices (KAP) regarding antibiotic use and self-medication among pregnant women. METHODS: We conducted a KAP survey of 301 pregnant women hospitalized at a tertiary hospital obstetric service in Cape Town, South Africa in November and December 2017, using an interviewer-administered 12 item questionnaire. We stratified analysis of attitudes and practices by participants' mean knowledge score (K-score) group (<6 versus ≥6 out of 7 questions). Multivariate models were built to identify independent predictors of antibiotic self-medication and K-score. RESULTS: The mean age of pregnant women was 29 (SD 6.1) years, 44/247 (17.8%) were nulliparous, 69/247 (27.9%) were HIV-infected, 228/247 (92.3%) had completed secondary school and 78/247 (31.6%) reported a monthly household income in the lowest category of ≤50-100 US dollars (USD). The mean K-score was 6.1 (SD 1.02) out of 7 questions. Sixteen percent of the cohort reported antibiotic self-medication, with higher rates among pregnant women with K-score <6 [18/48 (37.5%) versus 32/253 (12.6%); P<0.001]. The monthly household income category of >500 USD (the highest category) was the only predictor of antibiotic self-medication behaviour [adjusted OR=6.4 (95% CI 1.2-35.2), P=0.03]. CONCLUSIONS: Higher antibiotic knowledge scores are associated with lower rates of antibiotic self-medication, whereas higher household income is correlated with increasing self-medication behaviours. Education of pregnant women regarding the potential dangers of antibiotic self-medication and stricter enforcement of existing South African antibiotic prescribing and dispensing regulations are needed.

Prevalence, Predictors, and Successful Treatment Outcomes of Xpert MTB/RIF-identified Rifampicin-resistant Tuberculosis in Post-conflict Eastern Democratic Republic of the Congo, 2012-2017: A Retrospective Province-Wide Cohort Study.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. METHODS: of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan-Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. RESULTS: Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63-3.59), retreatment of TB (aOR 4.92, 95% CI 2.31-10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01-3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3-60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2-6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88-9.71). CONCLUSIONS: Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes.

Education and management of antimicrobials amongst nurses in Africa-a situation analysis: an Infection Control Africa Network (ICAN)/BSAC online survey.

Objectives: To assess the current involvement of nurses in the use and management of antimicrobials and their training in antimicrobial stewardship (AMS) across Africa. Methods: After a pilot study, an online questionnaire (SurveyMonkey) in both French and English was circulated via the Infection Control Africa Network (ICAN) mailing list to both members and non-members in Africa. The study was conducted from 26 May to 19 August 2016. Data were summarized in proportions and bar charts; proportions were compared using the χ2 test. A multivariate logistic regression model was built to identify independent factors associated with the practice of AMS. Results: While 96% of the 173 respondents were aware of the term 'AMS', 88.5% (146/165) undertook AMS tasks as part of their job; 91.9% (158/172) wanted to be more involved in AMS but 44.9% (71/158) reported there were barriers in doing so. AMS training was delivered to 36.7% (62/169) and 53.6% (90/168), respectively, during their undergraduate and postgraduate education. AMS training for healthcare workers in their institutions was reported by 50.3% (86/171), including training aimed at doctors (56.9%), pharmacists (76.7%), microbiologists (31.4%) and nurses (95.3%). However, 95.4% (164/172) of respondents asked for further education on AMS and the majority preferred AMS training to be part of the infection prevention curriculum (IPC) education. Three-quarters of institutions had an AMS initiative, but only ∼41% reported having seen a national AMS guideline. Conclusions: For Africa, we recommend AMS education at undergraduate level, AMS policies at institution and national levels and incorporating AMS training into the IPC for nurses.

Prevalence and risk factors of metabolic syndrome in HIV-infected adults at three urban clinics in a post-conflict setting, eastern Democratic Republic of the Congo.

OBJECTIVE: To determine the prevalence of and risk factors for metabolic syndrome (MS) in HIV-infected adults at three urban clinics in Bukavu, Democratic Republic of the Congo. DESIGN: Cross-sectional study. METHODS: From July to September 2016, baseline socio-demographics, risk factors and clinical characteristics were collected using a structured questionnaire or extracted from medical records. Fasting blood sugar and lipids were measured. MS was defined per the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and the International Diabetes Federation (IDF) criteria. Adjusted odds ratio (OR) was generated through multivariate logistic regression models. RESULTS: Of 495 participants, 356 (72%) were women and 474 (95.8%) were receiving antiretroviral therapy (ART). The median age (years) [interquartile range (IQR)] was 43 [36-51]. The overall prevalence of MS per NECP/ATP III and IDF criteria was 27% [95% CI: 20-35%] or 30% [95% CI: 23-38%], respectively. In a multivariate logistic regression, low physical activity (OR 2.47, 95% CI: 1.40-4.36); daily exposure to biomass fuel smoke (BMF) for more than 2 h (OR 2.18, 95% CI: 1.01-4.68); protease inhibitor containing ART (OR: 2.96, 95% CI: 1.07-8.18); and stavudine-containing ART regimen (OR: 2.57, 95% CI: 1.11-5.93) were independently associated with MS. CONCLUSIONS: MS was highly prevalent in this hospital-based study population. Beside known traditional risk factors and contribution of specific ART regimens to MS, daily exposure to BMF is new and of specific concern, necessitating targeted urgent prevention and management interventions.

Seroprevalence and associated risk factors of hepatitis C infection among diabetic patients in South-Kivu, Eastern Democratic Republic of the Congo: A cross-sectional study.

Background and Aims: Hepatitis C virus (HCV) infection and diabetes mellitus (DM) are two frequent diseases in the Democratic Republic of the Congo (DRC) and several studies seem to show a link between the two diseases worldwide. However, no study has evaluated this link in our country. The present study aimed at determining the seroprevalence of HCV in diabetic patients as well as associated risk factors. Methodology: A multicenter cross-sectional study allowed us to sample diabetic patients in two diabetic healthcare centers of Bukavu city in the eastern part of the DRC, from December 2020 to December 2022. A questionnaire was submitted to the diabetic patients to collect sociodemographic data, anamnestic data on risk factors for HCV infection, and clinical data on DM. These factors were analyzed based on anti-HCV serological results. Results: Among the 180 selected patients, 19 (10.6%) were tested positive for anti-HCV antibodies. After multivariate analysis, the identified factors influencing these outcomes were male sex (adjusted odds ratio [aOR]: 3.5, p = 0.027), dental extraction (aOR: 7.6, p = 0.001), and living in a privileged environment (aOR: 0.29, p = 0.03). The factors related to DM such as the type, the disease duration, or the usual type of treatment did not influence the serological results. Conclusion: This study shows that HCV seroprevalence in diabetic patients is very high compared with the general population. This suggests combined screening and management policies in this population.

Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study.

BACKGROUND: Neonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs. METHODS: The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Data for sepsis-associated factors in the four domains of health care, maternal, birth and neonatal, and living environment were collected for all mothers and neonates enrolled. Primary outcomes were clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality in neonates during the first 60 days of life. Incidence proportion of livebirths for clinically suspected sepsis and laboratory-confirmed sepsis and incidence rate per 1000 neonate-days for all-cause mortality were calculated. Modified Poisson regression was used to investigate factors associated with neonatal sepsis and parametric survival models for factors associated with all-cause mortality. FINDINGS: Between Nov 12, 2015 and Feb 1, 2018, 29 483 mothers and 30 557 neonates were enrolled. The incidence of clinically suspected sepsis was 166·0 (95% CI 97·69-234·24) per 1000 livebirths, laboratory-confirmed sepsis was 46·9 (19·04-74·79) per 1000 livebirths, and all-cause mortality was 0·83 (0·37-2·00) per 1000 neonate-days. Maternal hypertension, previous maternal hospitalisation within 12 months, average or higher monthly household income, ward size (>11 beds), ward type (neonatal), living in a rural environment, preterm birth, perinatal asphyxia, and multiple births were associated with an increased risk of clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality. The majority (881 [72·5%] of 1215) of laboratory-confirmed sepsis cases occurred within the first 3 days of life. INTERPRETATION: Findings from this study highlight the substantial proportion of neonates who develop neonatal sepsis, and the high mortality rates among neonates with sepsis in LMICs. More efficient and effective identification of neonatal sepsis is needed to target interventions to reduce its incidence and subsequent mortality in LMICs. FUNDING: Bill & Melinda Gates Foundation.

Laboratory-confirmed bloodstream infections in two large neonatal units in sub-Saharan Africa.

BACKGROUND: Epidemiological data on neonatal bloodstream infections (BSI) in sub-Saharan Africa are extremely limited. METHODS: A comparative analysis of laboratory-confirmed neonatal BSI episodes was conducted retrospectively in two large neonatal units in Botswana and South Africa (January 1 to December 31, 2017). Routine laboratory and ward register data were used to determine BSI rates, the pathogen spectrum, and BSI outcomes. RESULTS: In 2017, the Princess Marina Hospital (PMH) and Tygerberg Hospital (TBH) neonatal units admitted 1187 and 2826 neonates, respectively. The BSI incidence rate was 12.1/1000 patient-days (95% confidence interval (CI) 10.2-14.3) at PMH and 3.5/1000 patient-days (95% CI 2.9-4.1) at TBH (p < 0.0001). Most BSI episodes were hospital-acquired (260/284; 91.6%). The blood culture contamination rate was substantially higher at PMH than TBH (152/1116 (13.6%) vs 122/2559 (4.8%); p < 0.001). The crude mortality rate in neonates with BSI was 21.2% (53/250) and significantly higher at TBH than PMH (38/128 (29.7%) vs 15/122 (12.3%), p = 0.001). Factors independently associated with death were birth weight <1500 g (adjusted odds ratio (aOR) 2.8, 95% CI 1.3-6.4; p = 0.02) and male sex (aOR 2.1, 95% CI 1.1-3.7; p = 0.01). Klebsiella pneumoniae was the dominant BSI pathogen in both units, accounting for two-thirds of BSI, and was associated with a large infection outbreak at PMH. Antibiotic resistance rates were substantial in both neonatal units, particularly for K. pneumoniae (98/122 (80.3%), extended-spectrum beta-lactamase (ESBL)-producers) and Staphylococcus aureus (22/33 (66.7%), methicillin-resistant). CONCLUSIONS: BSI rates and associated mortality were substantial in these two neonatal units in sub-Saharan Africa. ESBL-producing K. pneumoniae remains a leading BSI and outbreak pathogen.

Global Tuberculosis Report 2020 - Reflections on the Global TB burden, treatment and prevention efforts.

The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods.

Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries.

Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause and burden of antimicrobial resistance in neonatal sepsis for seven LMICs in Africa and South Asia. A total of 36,285 neonates were enrolled in the BARNARDS study between November 2015 and December 2017, of whom 2,483 were diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) was the main cause of neonatal sepsis, with Serratia marcescens (n = 151), Klebsiella michiganensis (n = 117), Escherichia coli (n = 75) and Enterobacter cloacae complex (n = 57) also detected. We present whole-genome sequencing, antimicrobial susceptibility and clinical data for 916 out of 1,038 neonatal sepsis isolates (97 isolates were not recovered from initial isolation at local sites). Enterobacterales (K. pneumoniae, E. coli and E. cloacae) harboured multiple cephalosporin and carbapenem resistance genes. All isolated pathogens were resistant to multiple antibiotic classes, including those used to treat neonatal sepsis. Intraspecies diversity of K. pneumoniae and E. coli indicated that multiple antibiotic-resistant lineages cause neonatal sepsis. Our results will underpin research towards better treatments for neonatal sepsis in LMICs.

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS).

BACKGROUND: Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin-gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. METHODS: In BARNARDS, consenting mother-neonates aged 0-60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic-pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. FINDINGS: Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin-gentamicin, ceftazidime-amikacin, piperacillin-tazobactam-amikacin, and amoxicillin clavulanate-amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime-amikacin than for neonates treated with ampicillin-gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14-0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin-gentamicin; 286 (73·3%) to amoxicillin clavulanate-amikacin; 301 (77·2%) to ceftazidime-amikacin; and 312 (80·0%) to piperacillin-tazobactam-amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin-gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate-amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime-amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin-tazobactam-amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis. INTERPRETATION: Our data raise questions about the empirical use of combined ampicillin-gentamicin for neonatal sepsis in LMICs because of its high resistance and high rates of frequency of resistance and low probability of target attainment. Accessibility and affordability need to be considered when advocating antibiotic treatments with variance in economic health structures across LMICs. FUNDING: The Bill & Melinda Gates Foundation.

Maternal colonization or infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae in Africa: A systematic review and meta-analysis.

OBJECTIVE: To summarize published studies on the prevalence of and risk factors for maternal bacterial colonization and/or infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in pregnant and/or post-partum women in Africa. METHODS: A systematic review was conducted using the PubMed, Scopus, and Google Scholar databases. Bibliographies of included eligible studies were manually searched to identify additional relevant articles. No language restriction was applied. The timeframe of the search included all records from electronic database inception to July 15, 2017. A random-effects meta-analysis was performed to summarize the prevalence and the 95% confidence intervals (CI) of ESBL-E colonization or infection in pregnant or post-partum women in Africa. The meta-analysis was conducted using STATA IC 13.1 software and the metaprop function/plugin. RESULTS: Ten studies (seven on pregnant women and three on post-partum women) were included, documenting a 17% prevalence of maternal colonization with ESBL-E in Africa (95% CI 10-23%). The prevalence of ESBL-E in community isolates exceeded that in isolates from the hospital setting (22% vs. 14%). The most frequently reported ESBL-encoding gene was CTX-M (cefotaxime hydrolyzing capabilities). Data on risk factors for maternal ESBL-E colonization and infection are very limited. CONCLUSIONS: The prevalence of colonization and/or infection with ESBL-E in pregnant and post-partum women in Africa exceeds that reported from high- and middle-income settings, representing a risk for subsequent neonatal colonization and/or infection with ESBL-E.

Deliberate exposure of humans to chlorine-the aftermath of Ebola in West Africa.

BACKGROUND: During the recent Ebola outbreak, spraying of the environment and humans, including healthcare workers, with chlorine was wide spread in affected African countries; adverse clinical effects are reported here. METHODS: A cross sectional survey by interview of 1550 volunteers consisting of 500 healthcare workers (HCW), 550 Ebola survivors (EVD) and 500 quarantined asymptomatic Ebola contacts (NEVD) was conducted. Demographics, frequency of exposure to chlorine, clinical condition after chlorine exposure particularly eye, respiratory and skin conditions were noted. The length of time HCWs worked in Ebola Treatment Units (ETU), and use of personal protective equipment was recorded. Verbal consent was obtained from all participants and all responses remained anonymous. Permission and assistance from the guardian or parent was sought for those below 18 years of age. RESULTS: 493/500 HCW, 550/550 EVD and 477/500 NEVD were sprayed at least once with 0 · 5 % chlorine. Following even a single exposure, an increase in the number of eye (all three groups) and respiratory symptoms (in HCW & EVD) was reported (p < 0 · 001); after multiple exposure, respiratory and skin symptoms increased. In HCW, multiple vs single exposure was associated with an increase in respiratory (OR = 32 (95 % CI 22 -49) p < 0.001), eyes (OR = 30 (95 % CI 21 -43) p < 0.001) and skin conditions (OR = 22 (95 % CI 15-32) p < 0.001). The available personal protective equipment neither reduced nor prevented the adverse effects of chlorine. CONCLUSION: Reported exposure to chlorine has usually been accidental. Despite the lack of evidence as a recognised outbreak control measure, deliberate exposure of humans to chlorine spray was wide spread in Africa during the Ebola epidemic resulting in serious detrimental health effects on humans. We strongly recommend that this practice be banned and that alternative safer methods be used.