Colonisation of hospital surfaces from low- and middle-income countries by extended spectrum ß-lactamase- and carbapenemase-producing bacteria.

Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum ß-lactamases (blaCTX-M-15) and carbapenemases (blaNDM, blaOXA-48-like and blaKPC), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates. We determine presence of consistently dominant clones and their relatedness to strains causing neonatal sepsis. Higher prevalence of carbapenemases is observed in Pakistan, Bangladesh, and Ethiopia, compared to other countries, and are mostly found in surfaces near the sink drain. Klebsiella pneumoniae, Enterobacter hormaechei, Acinetobacter baumannii, Serratia marcescens and Leclercia adecarboxylata are dominant; ST15 K. pneumoniae is identified from the same ward on multiple occasions suggesting clonal persistence within the same environment, and is found to be identical to isolates causing neonatal sepsis in Pakistan over similar time periods. Our data suggests persistence of dominant clones across multiple time points, highlighting the need for assessment of Infection Prevention and Control guidelines.

Mortality associated with third-generation cephalosporin resistance in Enterobacterales bloodstream infections at eight sub-Saharan African hospitals (MBIRA): a prospective cohort study.

BACKGROUND: Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa. METHODS: We conducted a prospective, matched, parallel cohort study at eight hospitals across sub-Saharan Africa. We recruited consecutive patients of all age groups with laboratory-confirmed Enterobacterales bloodstream infection and matched them to at least one patient without bloodstream infection on the basis of age group, hospital ward, and admission date. Date of infection onset (and enrolment) was defined as the day of blood sample collection for culturing. Patients infected with bacteria with a cefotaxime minimum inhibitory concentration of 1 mg/L or lower were included in the third-generation cephalosporin-susceptible (3GC-S) cohort, and the remainder were included in the third-generation cephalosporin-resistant (3GC-R) cohort. The primary outcomes were in-hospital death and death within 30 days of enrolment. We used adjusted multivariable regression models to first compare patients with bloodstream infection against matched patients within the 3GC-S and 3GC-R cohorts, then compared estimates between cohorts. FINDINGS: Between Nov 1, 2020, and Jan 31, 2022, we recruited 878 patients with Enterobacterales bloodstream infection (221 [25·2%] to the 3GC-S cohort and 657 [74·8%] to the 3GC-R cohort) and 1634 matched patients (420 [25·7%] and 1214 [74·3%], respectively). 502 (57·2%) bloodstream infections occurred in neonates and infants (age 0-364 days). Klebsiella pneumoniae (393 [44·8%] infections) and Escherichia coli (224 [25·5%] infections) were the most common Enterobacterales species identified. The proportion of patients who died in hospital was higher in patients with bloodstream infection than in matched controls in the 3GC-S cohort (62 [28·1%] of 221 vs 22 [5·2%] of 420; cause-specific hazard ratio 6·79 [95% CI 4·06-11·37] from Cox model) and the 3GC-R cohort (244 [37·1%] of 657 vs 115 [9·5%] of 1214; 5·01 [3·96-6·32]). The ratio of these cause-specific hazard ratios showed no significant difference in risk of in-hospital death in the 3GC-R cohort versus the 3GC-S cohort (0·74 [0·42-1·30]). The ratio of relative risk of death within 30 days (0·82 [95% CI 0·53-1·27]) also indicated no difference between the cohorts. INTERPRETATION: Patients with bloodstream infections with Enterobacterales bacteria either resistant or susceptible to third-generation cephalosporins had increased mortality compared with uninfected matched patients, with no differential effect related to third-generation cephalosporin-resistance status. However, this finding does not account for time to appropriate antibiotic treatment, which remains clinically important to optimise. Measures to prevent transmission of Enterobacterales could reduce bloodstream infection-associated mortality from both drug-resistant and drug-susceptible bacterial strains in Africa. FUNDING: Bill & Melinda Gates Foundation.

Circumstances for treatment and control of invasive Enterobacterales infections in eight hospitals across sub-Saharan Africa: a cross-sectional study.

Background: Bloodstream infections caused by Enterobacterales show high frequency of antimicrobial resistance (AMR) in many Low- and Middle-Income Countries. We aimed to describe the variation in circumstances for management of such resistant infections in a group of African public-sector hospitals participating in a major research study. Methods: We gathered data from eight hospitals across sub-Saharan Africa to describe hospital services, infection prevention and antibiotic stewardship activities, using two WHO-generated tools. We collected monthly cross-sectional data on availability of antibiotics in the hospital pharmacies for bloodstream infections caused by Enterobacterales. We compared the availability of these antibiotics to actual patient-level use of antibiotics in confirmed Enterobacterales bloodstream infections (BSI). Results: Hospital circumstances for institutional management of resistant BSI varied markedly. This included self-evaluated infection prevention level (WHO-IPCAF score: median 428, range 155 to 687.5) and antibiotic stewardship activities (WHO stewardship toolkit questions: median 14.5, range 2 to 23). These results did not correlate with national income levels. Across all sites, ceftriaxone and ciprofloxacin were the most consistently available antibiotic agents, followed by amoxicillin, co-amoxiclav, gentamicin and co-trimoxazole. There was substantial variation in the availability of some antibiotics, especially carbapenems, amikacin and piperacillin-tazobactam with degree of access linked to national income level. Investigators described out-of-pocket payments for access to additional antibiotics at 7/8 sites. The in-pharmacy availability of antibiotics correlated well with actual use of antibiotics for treating BSI patients. Conclusions: There was wide variation between these African hospitals for a range of important circumstances relating to treatment and control of severe bacterial infections, though these did not all correspond to national income level. For most antibiotics, patient-level use reflected in-hospital drug availability, suggesting external antibiotics supply was infrequent. Antimicrobial resistant bacterial infections could plausibly show different clinical impacts across sub-Saharan Africa due to this contextual variation.

Early-Onset Neonatal Sepsis in Low- and Middle-Income Countries: Current Challenges and Future Opportunities.

Neonatal sepsis is defined as a systemic infection within the first 28 days of life, with early-onset sepsis (EOS) occurring within the first 72h, although the definition of EOS varies in literature. Whilst the global incidence has dramatically reduced over the last decade, neonatal sepsis remains an important cause of neonatal mortality, highest in low- and middle-income countries (LMICs). Symptoms at the onset of neonatal sepsis can be subtle, and therefore EOS is often difficult to diagnose from clinical presentation and laboratory testing and blood cultures are not always conclusive or accessible, especially in resource limited countries. Although the World Health Organisation (WHO) currently advocates a ß-lactam, and gentamicin for first line treatment, availability and cost influence the empirical antibiotic therapy administered. Antibiotic treatment of neonatal sepsis in LMICs is highly variable, partially caused by factors such as cost of antibiotics (and who pays for them) and access to certain antibiotics. Antimicrobial resistance (AMR) has increased considerably over the past decade and this review discusses current microbiology data available in the context of the diagnosis, and treatment for EOS. Importantly, this review highlights a large variability in data availability, methodology, availability of diagnostics, and aetiology of sepsis pathogens.

A mini- national surveillance study of resistance profiles of Staphylococcus Aureus isolated from clinical specimens across hospitals in Nigeria.

BACKGROUND: Infections with Staphylococcus aureus cause significant morbidity and mortality worldwide. Resistant strains of S. aureus to commonly used antibiotics are being increasingly encountered in clinical practice, necessitating the need to determine the resistance pattern in Nigeria. METHODS: Antibiotic susceptibility testing was performed on 360 S. aureus isolates from clinical specimen from seven hospitals across the six geo-political regions of Nigeria using Kirby Bauer disc diffusion technique, and E-test for vancomycin. Cefoxitin 30 µg disc was used to determine methicillin resistance, and D-test for inducible clindamycin resistance. RESULTS: Methicillin-resistant S. aureus was confirmed in 176 (48.9%) of the isolates, 346 (96%) for penicillin G and 311 (86.4%) for trimethoprim. 175 (99.4%) of the 176 resistant to methicillin were susceptible to vancomycin. Linezolid, tigecycline, chloramphenicol and clindamycin had susceptibilities of 341 (94.7%), 332 (92.2%), 298 (82.8%) and 290 (80.6%) respectively. Inducible clindamycin resistance was elucidated in 25 (29.1%) of the 86 isolates. Generally, MRSA isolates were more resistant than methicillin-sensitive S. aureus (MSSA) to all antibiotics tested. CONCLUSION: Staphylococcus aureus rates of resistance are high and call for urgent action such as antibiotic stewardship programmes and periodic surveillance to enhance clinical outcomes. While targeted therapy is preferred, options for empiric treatment include chloramphenicol, clindamycin, linezolid or vancomycin.

The efficacy of intermittent preventive therapy in the eradication of peripheral and placental parasitemia in a malaria-endemic environment, as seen in a tertiary hospital in Abuja, Nigeria.

OBJECTIVE: To determine whether intermittent preventive therapy in pregnancy (IPTp) eradicates peripheral and placental malaria and improves birth weight. METHOD: A cross-sectional study was conducted of 426 pregnant mothers on IPTp with sulphadoxine-pyrimethamine against malaria who presented in labor, at National Hospital Abuja, Nigeria between January and June 2017. The hospital is within the malaria-endemic zone of West Africa. Consenting pregnant women with uncomplicated singleton term pregnancy who had antenatal care in the hospital and lived in the study area for at least 6 months were consecutively recruited. Peripheral and placental blood were collected and examined for malaria parasite by microscopy. Babies were weighed at birth. RESULTS: The prevalence of peripheral malaria parasitemia and placental parasitization were 12.9% (95% confidence interval [CI] 10.0-16.6) and 9.4% (95% CI 7.0-12.7), respectively. Parasite density in both peripheral parasitemia and placental parasitization was low among the women that took IPTp, decreasing with increasing doses, with no parasitemia or parasitization in women that took up to three doses. Birth weight was lower in babies of mothers with plasmodium infestation than in those without infestation (P<0.001, P=0.024). CONCLUSION: IPTp reduces both peripheral parasitemia and placental parasitization, with the capacity to eliminate or prevent them. IPTp also reduces low birth weight.

Profiles of acute bacterial meningitis isolates in children in National Hospital, Abuja.

BACKGROUND: Acute bacterial meningitis (ABM) is an important cause of morbidity and mortality throughout the world. It is an acute medical emergency that requires urgent rational antibiotic therapy, especially in neonates and young infants. Determining the pattern and susceptibility of isolates of ABM among children for prompt treatment of this important cause of mortality and morbidity is very important. This study determined the types and the antimicrobial susceptibility pattern of ABM isolates among children at the National Hospital, Abuja. MATERIALS AND METHODS: This is a retrospective study carried out at the National Hospital Abuja (NHA), Nigeria. Laboratory data for a period of 3 years, January 2010-December 2013 were reviewed, and all bacterial isolates and their antibiotics sensitivity testing results for children aged 0-15 years, and other relevant information extracted and analyzed. Study center was the NHA. RESULTS: Twenty-eight bacterial pathogens were isolated from a total of 542 cerebrospinal specimens over the study period, giving a yield of 5.2%. The four most common pathogens isolated were Staphylococcus aureus (32.2%), Klebsiella pneumoniae (21.5%), Streptococcus pneumoniae (17.6%), and Escherichia coli (14.3%). Whereas, 28.6% of all the infections occurred in neonates alone, children 2 years and below had 85.7% of all the infections, with male preponderance. Isolates of S. aureus and S. pneumonia tested were both 100% susceptible to amoxicillin-clavulanic acid and Cefuroxime; S. pneumoniae was equally sensitive to Ceftriaxone. K. pneumoniae was 100% sensitive to Imipenem, but 83% to ceftriaxone. 75% of the isolated E. coli strains were sensitive to ceftriaxone, amoxicillin-clavulanic acid, and amikacin, 100% sensitive to imipenem. CONCLUSION: Meningitis in children as seen in the National hospital is almost equally caused by both Gram-positive and Gram-negative organisms, predominantly by S. aureus, S. pneumoniae, K. pneumoniae, and E. coli. Available drugs remain active against these organisms.

Dual Path Platform HIV 1/2 assay: evaluation of a novel rapid test using oral fluids for HIV screening at the National Hospital in Abuja, Nigeria.

HIV/AIDS disease is endemic in Nigeria and associated with stigmatization. Availability of a reliable rapid testing kit and procedure will increase uptake of services. The study aimed to determine the correlation between detection of HIV antibodies in blood to that in oral fluid and to determine the sensitivity and specificity of the Dual Path Platform (DPP) testing kit using oral fluid samples. HIV antibodies detected in oral mucosa transudate and whole capillary blood from HIV-positive, high-risk and low-risk participants were compared with results obtained with whole venous blood from the same participants tested with Determine and Western blot (for discordant cases). Oral fluid test has sensitivity and specificity of 100% relative to Determine rapid assay, while whole capillary blood test has sensitivity of 100% and specificity of 99.5%. DPP oral fluid test is a reliable point-of-care test and may be deployed in large-scale screening exercises.

Bacteriological profile of neonatal septicaemia in a tertiary hospital in Nigeria.

BACKGROUND: Neonatal septicaemia is an important cause of morbidity and mortality. Knowledge of the bacteriological profile of the aetiologic agents is very important and helps to reduce the associated mortality in neonatal septicaemia. OBJECTIVE: To determine the bacteriological profile of common aetiologic agents of neonatal septicaemia and their antibiotics sensitivity pattern. METHOD: This study was a retrospective review of all the 390 neonatal blood cultures carried out in the Department of Clinical Microbiology and Parasitology of the National Hospital Abuja, Nigeria over three years (Jan 2002-Dec 2004). RESULT: The 390 neonatal samples constituted 25% of all blood samples received in the laboratory during the period under review. Twenty-two percent were positive for bacterial growth, yielding gram-negative bacilli (GNB) and gram- positive cocci (GPC) in almost equal proportion, predominantly Klebsiella pneumoniae (86% of GNB) and Staphylococcus aureus (81% of GPC). Although the Klebsiella pneumoniae were multiply-resistant and showed resistance pattern suggestive of Extended-Spectrum Beta Lactamase (ELBS) production they were 100% sensitive to imipenem. The sensitivity of the Staphylococcus aureus isolates to amoxicillin-clavulanic acid, cefuroxime, ciprofloxacin, chloramphenicol and erythromycin were 89%, 85%, 75%, 71% and 64% respectively. CONCLUSION: A sustainable antibiotic susceptibility surveillance programme coupled with good infection control practices and rational antibiotics use will reduce infection rate, ensure better therapeutic success and prolong the efficacy of available antimicrobials.