Household cockroaches carry CTX-M-15-, OXA-48- and NDM-1-producing enterobacteria, and share beta-lactam resistance determinants with humans.

BACKGROUND: This study was designed to investigate whether household cockroaches harbor cephalosporin-resistant enterobacteria that share resistance determinants with human inhabitants. From February through July 2016, whole cockroach homogenates and human fecal samples from 100 households were cultured for cephalosporin-resistant enterobacteria (CRe). The CRe were examined for plasmid-mediated AmpC, ESBL, and carbapenemase genes; antibiotic susceptibility patterns; and conjugative transfer of antibiotic resistance mechanisms. Clonal associations between CRe were determined by multi-locus sequence typing (MLST). RESULTS: Twenty CRe were recovered from whole cockroach homogenates from 15 households. The prevalence of households with cockroaches that harbored CRe, AmpC- (based on phenotype, with no identifiable blaAmpC genes), ESBL-, and carbapenemase-producers were 15, 4, 5%(2 blaCTX-M-15/TEM-1; 1 blaCTX-M-15/TEM-4; 1 blaTEM-24; 1 blaSHV-4) and 3%(2 blaNDM-1 genes and 1 blaOXA-48 gene), respectively. Overall, 20 CRe were recovered from 61 fecal samples of inhabitants from all 15 households that had cockroach samples positive for CRe. Of these, 5CRe (1 per household) were positive for ESBLs (blaTEM-24, blaTEM-14, blaCTX-M-15/TEM-4, blaSHV-3, blaCTX-M-15/TEM-1) and none carried AmpCs or carbapenemases. From 4% of households, the pair of cockroach and human CRe shared the same sequence type (ST), clonal complex (CC), antibiogram, and conjugable bla gene sequence (house 34, E. coli ST9/CC20-blaTEM-4; house 37, E. coli ST44/CC10-blaCTX-15/TEM-4; house 41, E. coli ST443/CC205-blaCTX-15/TEM-1; house 49, K. pneumoniae ST231/CC131-blaSHV-13). CONCLUSION: The findings provide evidence that household cockroaches may carry CTX-M-15-, OXA-48- and NDM-1-producers, and share clonal relationship and beta-lactam resistance determinants with humans.

Antibiotic use in surgical units of selected hospitals in Ghana: a multi-centre point prevalence survey.

BACKGROUND: Improper use of antibiotics leads to the emergence of resistant microorganisms as well as drug toxicity, increased healthcare costs, morbidity and mortality. Globally, an estimated 25-68% of hospitalized patients receive suboptimal antibiotic regimes. Information on the extent of this problem in Ghana is currently limited, particularly in surgical units. To strategize for interventions, we estimated the antibiotic use prevalence in surgical departments in a country-wide point prevalence survey (PPS) in Ghana. METHODS: Between October 2016 and December 2016, we conducted a cross-sectional multi-center country-wide PPS. This involved an audit of in-patients' records from all units/departments of ten systematically selected hospitals in Ghana. Data were collected with a standardized questionnaire, adopted from the European Centre for Disease Prevention and Control. In this report, we present data on antibiotic use from the surgical units. RESULTS: Of 2107 eligible patients included in the PPS, 540 patients were identified in surgical units, of which 70.7% (382/540) received antibiotic therapy. A total of 636 antibiotic prescriptions were issued to these surgical patients; 224 (58.6%) for treatment, including 50 for treatment of hospital-acquired infections, and 144 (37.7%) for prophylaxis (medical and surgical). Median duration of antibiotic therapy prior to the survey was 5 days (interquartile range (IQR): 3-8 days). Surgical prophylaxis was administered for longer than the recommended one day in 107 of 144 (88.4%) patients. The choice of antibiotics was largely similar for community- and hospital-acquired infections as well as for prophylaxis. Only 3.7% of patients had microbiological analysis done on clinical samples. CONCLUSION: We found a high prevalence of antibiotic use, with the choice of antibiotics, in some cases, inconsistent with the country's treatment guidelines. Antibiotics were administered for long duration including antibiotics for prophylactic purposes and the majority was started without supporting microbiological analysis. Prescription practices that encourage rational use of antibiotics guided by microbiology and enforcement of antibiotic policy guidelines should be the target for future interventions.

Trichomonas vaginalis infection and the diagnostic significance of detection tests among Ghanaian outpatients.

BACKGROUND: There is little data on Trichomonas vaginalis infection in Ghana. This study evaluated the prevalence of trichomoniasis using different diagnostic methods and determined the risk factors for infection in patients. METHODS: A structured questionnaire was administered. Vaginal swabs, urethral swabs and urine specimens were obtained from consenting patients; and the samples processed following standard protocols. The presence of T. vaginalis was determined using wet mount microscopy and polymerase chain reaction (PCR) as gold standard. We also assessed the diagnostic performance the JD's Trichomonas V® rapid antigen test to inform clinical practice. RESULTS: The PCR assay detected T. vaginalis positivity in 64 of 150 patients (42.6, 95%CI:35.0, 50.6) including all positive samples of wet mount microscopy and JD's Trichomonas V® test. Wet mount microscopy showed low sensitivity (31.6%), high specificity (100%), moderate positive predictive value (75.0%), moderate positive likelihood ratio (3.0), and weak agreement (Cohen's kappa, 0.283) with PCR assay. The JD's Trichomonas V® test displayed lower sensitivity (25.0%), specificity (83.3%), and weaker measure of agreement (Cohen's kappa, 0.233) with PCR. In multivariate analysis, the strongest independent predictor for T. vaginalis was female gender [adjusted odds ratio (AOR), 24.89; 95% confidence interval (CI): 10.58, 51.21; P-value< 0.001]. Knowledge of STI showed a protective effect against infection with the parasite (AOR, 0.13; 95%CI: 0.07, 0.29; P-value< 0.017). CONCLUSION: The sensitivity of wet mount microscopy was low for T. vaginalis screening in our region. The JD's Trichomonas V® test should not be considered as an alternative test. We recommend mandatory PCR assay for confirmation of negative wet mount results.

Antibiotic prescribing in paediatric inpatients in Ghana: a multi-centre point prevalence survey.

BACKGROUND: Excessive and inappropriate use of antibiotics in hospitalised patients contributes to the development and spread of antibiotic resistance. Implementing a stewardship programme to curb the problem requires information on antibiotic use. This study describes a multicentre point prevalence of antibiotic use among paediatric inpatients in Ghana. METHODS: Data were extracted from a multicentre point prevalence survey of hospital acquired infections in Ghana. Data were collected between September 2016 and December 2016 from ten hospitals through inpatient folder and chart reviews using European Centre for Disease Control (ECDC) adapted data collection instrument. From each site, data were collected within a 12-h period (8 am to 8 pm) by a primary team of research investigators and a select group of health professionals from each participating hospital. RESULTS: Among 716 paediatric inpatients, 506 (70.6%; 95% confidence interval (CI): 67.2 to 74.0%) were on antibiotics. A significant proportion of antibiotics (82.9%) was prescribed for infants compared to neonates (63.9%) and adolescents (60.0%). The majority of patients (n = 251, 49.6%) were prescribed two antibiotics at the time of the survey. The top five classes of antibiotics prescribed were third generation cephalosporins (n = 154, 18.5%) aminoglycosides (n = 149, 17.9%), second generation cephalosporins (n = 103,12.4%), beta lactam resistant penicillins (n = 83, 10.0%) and nitroimidazoles (n = 82, 9.9%). The majority of antibiotics (n = 508, 61.0%) were prescribed for community acquired infections. The top three agents for managing community acquired infections were ceftriaxone (n = 97, 19.1%), gentamicin (n = 85, 16.7%) and cefuroxime (n = 73, 14.4%). CONCLUSION: This study points to high use of antibiotics among paediatric inpatients in Ghana. Cephalosporin use may offer an important target for reduction through antibiotic stewardship programmes.

Physicians' knowledge, attitudes, and perceptions concerning antibiotic resistance: a survey in a Ghanaian tertiary care hospital.

BACKGROUND: Understanding the knowledge, attitudes and practices of physicians towards antibiotic resistance is key to developing interventions aimed at behavior change. The survey aimed to investigate physicians' knowledge and attitudes towards antibiotic resistance in a tertiary-care hospital setting in Ghana. METHODS: We conducted a cross-sectional respondent-driven survey using a 40-item, anonymous, voluntary, traditional paper-and-pencil self-administered questionnaire among 159 physicians at Korle-Bu Teaching Hospital. Single and multi-factor analysis were conducted to assess the study objectives. RESULTS: The survey was completed by 159 of 200 physicians (response rate of 79.5%). Of physicians, 30.1% (47/156) perceived antibiotic resistance as very important global problem, 18.5% (29/157) perceived it as very important national problem and only 8.9% (14/157) thought it as a very important problem in their hospital. Methicillin resistant Staphylococcus aureus was the most known about antibiotic resistant bacteria of public health importance followed by extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem resistant Enterobacteriaceae (CRE) and vancomycin resistant enterococci (VRE). In multiple logistic regression analysis, senior physicians were nearly 3 times more likely to know about CRE than junior physicians. The odds of knowing about VRE increased over 4.5 times from being a junior to becoming senior physician. Among junior physicians, age had no associated effect on their knowledge of VRE or CRE. CONCLUSIONS: Physicians in this survey showed variable knowledge and perceptions on antibiotic resistance. Introducing educational programs on antibiotic resistance would be a useful intervention and should focus on junior physicians.

Trichomoniasis and associated co-infections of the genital tract among pregnant women presenting at two hospitals in Ghana.

BACKGROUND: Trichomonas vaginalis (TV) infection is the most prevalent non-viral sexually transmitted pathogen worldwide. Among pregnant women, the infection may cause adverse birth outcomes such as premature rupture of membranes and premature labour. In view of the paucity of information relating to TV among Ghanaian pregnant women, this study investigated its prevalence and associated co-infections among pregnant women. METHODS: High vaginal swabs were obtained from 99 pregnant women using sterile cotton swab sticks. Wet preparation, Grams staining, culturing, coagulase and sensitivity testing were carried out to determine the presence of TV and associated microorganisms. RESULTS: The prevalence of TV among the pregnant women was found to be 20.2% (n = 20). Concurring with Trichomoniasis, 75% (n = 15) of participants had other infections such as Candida with prevalence of 53% (n = 8), Proteus infection - 20% (n = 3), Streptococcus infection - 13% (n = 2) and other GNRs and Gonococci having 7% each (n = 1). Moreover, there was 86.9% (n = 86) prevalence of Staphylococcus spp. among study participants. There was statistically significant correlation between TV and Gonococci infection at a correlation co-efficient of 0.107 (P < 0.05) as well as significant correlation between TV and Proteus spp. at a correlation co-efficient of 0.189 (P < 0.05). TV infection was high (60%) among the most sexually active age group (19 to 29 yrs). CONCLUSION: There was 20.2% prevalence of TV among the pregnant women presenting at the hospitals, with Gonococci and Proteus infections being statistically significant associated infections.

Neonatal bloodstream infections in a Ghanaian Tertiary Hospital: Are the current antibiotic recommendations adequate?

BACKGROUND: Diagnosis of bloodstream infections (BSI) in neonates is usually difficult due to minimal symptoms at presentation; thus early empirical therapy guided by local antibiotic susceptibility profile is necessary to improve therapeutic outcomes. METHODS: A review of neonatal blood cultures submitted to the microbiology department of the Korle-Bu Teaching Hospital was conducted from January 2010 through December 2013. We assessed the prevalence of bacteria and fungi involved in BSI and the susceptibility coverage of recommended empiric antibiotics by Ghana Standard Treatment guidelines and the WHO recommendations for managing neonatal sepsis. The national and WHO treatment guidelines recommend either ampicillin plus gentamicin or ampicillin plus cefotaxime for empiric treatment of neonatal BSI. The WHO recommendations also include cloxacillin plus gentamicin. We described the resistance profile over a 28-day neonatal period using multivariable logistic regression analysis with linear or restricted cubic splines. RESULTS: A total of 8,025 neonatal blood culture reports were reviewed over the four-year period. Total blood culture positivity was 21.9 %. Gram positive organisms accounted for most positive cultures, with coagulase negative staphylococci (CoNS) being the most frequently isolated pathogen in early onset infections (EOS) (59.1 %) and late onset infections (LOS) (52.8 %). Susceptibility coverage of early onset bacterial isolates were 20.7 % to ampicillin plus cefotaxime, 32.2 % to the combination of ampicillin and gentamicin, and 71.7 % to cloxacillin plus gentamicin. For LOS, coverage was 24.6 % to ampicillin plus cefotaxime, 36.2 % to the combination ampicillin and gentamicin and 63.6 % to cloxacillin plus gentamicin. Cloxacillin plus gentamicin remained the most active regimen for EOS and LOS after exclusion of BSI caused by CoNS. For this regimen, the adjusted odds of resistance decreased between 12-34 % per day from birth to day 3 followed by the slowest rate of resistance increase, compared to the other antibiotic regimen, thereafter until day 28. The trend in resistance remained generally unchanged after excluding data from CoNS. Multidrug resistant isolates were significantly (p-value <0.001) higher in LOS (62.4 %, n = 555/886) than in EOS (37.3 %, n = 331/886). CONCLUSIONS: There is low antibiotic susceptibility coverage for organisms causing neonatal bloodstream infections in Korle-Bu Teaching Hospital when the current national and WHO recommended empiric antibiotics were assessed. A continuous surveillance of neonatal BSI is required to guide hospital and national antibiotic treatment guidelines for neonatal sepsis.

Trends in paediatric and adult bloodstream infections at a Ghanaian referral hospital: a retrospective study.

BACKGROUND: Bloodstream infections (BSI) are life-threatening emergencies. Identification of the common pathogens and their susceptibility patterns is necessary for timely empirical intervention. METHODS: We conducted a 4-year retrospective analysis of blood cultures from all patients excluding neonates at the Korle-Bu Teaching hospital, Ghana, from January 2010 through December 2013. Laboratory report data were used to determine BSI, blood culture contamination, pathogen profile, and antimicrobial resistance patterns. RESULTS: Overall, 3633 (23.16 %) out of 15,683 blood cultures were positive for various organisms. Pathogen-positive cultures accounted for 1451 (9.3 %, 95 % CI 8.5-9.8 %). Infants recorded the highest true blood culture positivity (20.9 %, n = 226/1083), followed by the elderly (13.3 %, n = 80/601), children (8.9 %, n = 708/8000) and adults (7.2 %, n = 437/6000) (p = 0.001 for Marascuilo's post hoc). Overall occurrence of BSI declined with increasing age-group (p = 0.001) but the type of isolates did not vary with age except for Citrobacter, Escherichia coli, Klebsiella, Salmonella, and Enterococcus species. Gram negative bacteria predominated in our study (59.8 %, n = 867/1451), but the commonest bacterial isolate was Staphylococcus aureus (21.9 %, n = 318/1451)-and this trend run through the various age-groups. From 2010 to 2013, we observed a significant trend of yearly increase in the frequency of BSI caused by cephalosporin-resistant enterobacteria (Chi square for trend, p = 0.001). Meropenem maintained high susceptibility among all Gram-negative organisms ranging from 96 to 100 %. Among Staphylococcus aureus, susceptibility to cloxacillin was 76.6 %. CONCLUSION: Our study shows a significantly high blood culture positivity in infants as compared to children, adults and the elderly. There was a preponderance of S. aureus and Gram-negative bacteria across all age-groups. Meropenem was the most active antibiotic for Gram-negative bacteria. Cloxacillin remains a very useful anti-staphylococcal agent.

Genetic characterization of TEM-type ESBL-associated antibacterial resistance in Enterobacteriaceae in a tertiary hospital in Ghana.

BACKGROUND: Antibiotic resistance due to the presence of extended-spectrum beta-lactamases (ESBLs) among Enterobacteriaceae is a worldwide problem. Data from Ghana regarding this resistance mechanism is limited. This study was designed to investigate the presence of TEM-type ESBL genes, their locations and their conjugabilities in clinical isolates of enterobacteria collected from the Korle-Bu Teaching Hospital in Ghana. METHODS: Study isolates were characterized with respect to ESBL phenotype, TEM-type ESBL gene detection, location of the ESBL gene(s) and conjugability of the ESBL phenotype using nalidixic acid-resistant Escherichia coli K-12 as recipient. Phenotyping was by Kirby Bauer disk diffusion using cefpodoxime, ceftazidime, cefotaxime and their combinations with clavulanate. Gene detections were by PCR using blaTEM primers. RESULTS: Overall, 37.96 % of 137 clinical isolates showed ESBL phenotype. The ESBLs occurred mostly in Klebsiella spp. (42.3 %) and then Escherichia coli (34.6 %). The TEM gene was detected in 48.1 % of ESBL-positive isolates and was determined to be plasmid-borne in 24 of 25 blaTEM detections. Overall, 62.7 % of TEM-producing isolates transferred the ESBL phenotype by conjugation. CONCLUSIONS: The results highlight the presence of TEM-type ESBLs in the Korle-Bu Teaching Hospital and show considerable risk of environmental contamination through the urine of infected persons. An inhibition zone chart was generated which indicates the possible presence of complex beta-lactamase types. The data points to the fact that the ESBL-producing bacteria may disseminate this resistance mechanism via conjugation.

Salmonella blood stream infections in a tertiary care setting in Ghana.

BACKGROUND: Despite the clinical significance of Salmonella infections, surveillance data worldwide remains limited and is more so exemplified by the lack of reports from Africa especially in eastern, central and western Africa. This study reports on Salmonella serotypes as significant causes of blood stream infections (BSI) and multidrug antibiotic resistance at Korle-Bu Teaching Hospital in Accra, Ghana. METHODS: Antibiogram patterns, seasonal variations in disease incidence and predisposing factors for infection with Salmonella serotypes were analyzed retrospectively over a 4-year period from January 2010 to December 2013. Blood cultures were processed with BACTEC 9240 blood culture system. Speciation was done with BBL Crystal Enteric/Nonfermenter identification system®, and with slide agglutination using specific antisera. Antimicrobial susceptibility testing was carried out by the Kirby-Bauer disc diffusion method according to Clinical and Laboratory Standard Institute guidelines. RESULTS: We report a 6.5% (n = 181/2768) prevalence of Salmonella bacteraemia at the Korle-Bu Teaching Hospital; with a preponderance of non-typhoidal salmonellae (NTS) over typhoidal salmonella (TS) (n = 115/181, 63.5% versus n = 66/181, 36.5%; P-value <0.002). Children under 5 years bore the brunt of the disease (n = 93/174, 53.4%). Resistance to ciprofloxacin (n = 1/127, 0.7%), amikacin (n = 3/81, 3.7%), and cefotaxime (n = 6/99, 6.1%) remained low, despite high levels of multidrug resistant Salmonella phenotypes (n = 81/181, 44.2%). In multivariate analysis, and among patients with Salmonella BSI, those < 1 year old had reduced risk of non-typhoidal infections [Odds ratio, 0.51; 95% confidence interval (95% CI), 0.16-0.92, P-value 0.021]. Similarly, patients with cefuroxime resistant strans were at increased risk of having multidrug resistant Salmonella BSI (OR, 8.97; 95% CI, 3.62-24.15; P-value, 0.001). CONCLUSIONS: Salmonellae, predominantly NTS, account for a reasonable low proportion of positive blood cultures in our tertiary care setting; but with significant multidrug resistant phenotypes and low ciprofloxacin and cefotaxime resistance.

Extended-spectrum beta-lactamases in clinical isolates of Escherichia coli and Klebsiella pneumoniae recovered from patients at the Tamale Teaching Hospital, Ghana.

INTRODUCTION: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae are pathogens of significant public health interest for which new antibiotics are urgently needed. AIM: To determine the prevalence of ESBLs in E. coli and K. pneumoniae isolates from patients attending the Tamale Teaching Hospital (TTH) in Ghana. METHODOLOGY: The study was a cross-sectional study involving convenience sampling of E. coli and K. pneumoniae isolates from consenting patients' clinical specimens, between April and June 2015. Antimicrobial susceptibility test was performed, and ESBL-producer phenotypes were further screened for BlaTEM, BlaSHV, and BlaCTX-M genes. Patients' clinical data were additionally collected using a structured questionnaire. RESULTS: Of the 150 non-duplicate E. coli and K. pneumoniae isolates identified, 140 were confirmed as E. coli (84%, n = 117) and K. pneumoniae (16%, n = 23). Of these, sixty-two (44%) [E. coli (84%; n = 52); K. pneumoniae (16%; n = 10)] phenotypically expressed ESBLs. The proportion of ESBL-producing isolates was higher in adults (15-65 years) than in neonates (< 28 days) (p = 0.14). Most of the isolates showed a high percentage resistance to ampicillin (96%) and tetracycline (89%), but a relatively lower resistance to amikacin (36%). No isolate was resistant to meropenem. More ESBL producers were multidrug resistant compared to non-ESBL-producers [23% (14/62) versus 18% (14/78); p = 0.573]. Overall, 74% (n = 46) of the ESBL genotypes expressed BlaCTX-M-1 genes, followed by 63% (n = 39) BlaTEM, and 16% (n = 10) BlaSHV. The study showed a high prevalence of ESBL-positive E. coli and K. pneumoniae, mostly CTX-M-1 producers at TTH. CONCLUSION: Routine laboratory ESBL screening is warranted to inform patient management.

Antibiotic consumption trends in Ghana: analysis of six-years pharmacy issue data from a secondary healthcare facility.

Background: Surveillance of hospital antibiotic consumption provides data to inform corrective action and for monitoring antimicrobial stewardship activities. This study described antibiotic consumption patterns from 2016 through 2021 at a secondary healthcare facility in Ghana. Methods: Using the WHO methodology for surveillance of antimicrobial consumption in hospitals, we analysed a 6-year pharmacy issue data at the Eastern Regional Hospital. We report on the defined daily dose (DDD) per 100 patients, types of antibiotics consumed according to Anatomic Therapeutic Classification (ATC), WHO AWaRe classification; trends in antibiotic consumption and expenditure per DDD of antibiotics consumed. Results: Over the period, the mean (±standard deviation) antibiotic consumption rate was 256.7 ±â€Š33 DDD/100 patients per year. A linear regression model showed an insignificant decreasing trend in antibiotic consumption (coefficient for time -0.561; P = 0.247). The top three consumed antibiotics in DDD/100 patients at ATC level 5 were amoxicillin-clavulanate (n = 372.6), cefuroxime (n = 287.4) and sulfamethoxazole-trimethoprim (n = 145.8). The yearly Access-to-Watch ratio decreased from 2.4 in 2016 to 1.2 in 2021. The mean yearly cost of antibiotics was $394 206 ±â€Š57 618 US dollars. The top three antibiotics consumed in terms of cost were clindamycin $718 366.3, amoxicillin-clavulanate $650 928.3 and ceftriaxone $283 648.5. Conclusion: This study showed a sturdy rate of antibiotic consumption over the 6-year period with a year-on-year decrease in the Access-to-Watch antibiotic ratio. Data from pharmacy drug issues offer an opportunity to conduct antibiotic consumption surveillance at the hospital and national level in Ghana.

High level of colonization with third-generation cephalosporin-resistant Enterobacterales in African community settings, Ghana.

A cross-sectional survey was conducted in eight Ghanaian communities to investigate the extent of intestinal colonization with 3rd-generation cephalosporin-resistant Enterobacterales. The study collected faecal samples and corresponding lifestyle data from 736 healthy residents to assess the occurrence of cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae, with a focus on genotypes of plasmid-mediated ESBLs, AmpCs, and carbapenemases. The results showed that 371 participants (50.4%) carried 3rd-generation cephalosporin-resistant E. coli (n=362) and K. pneumoniae (n=9). Most of these were ESBL-producing E. coli (n=352, 94.9%), carrying CTX-M genes (96.0%, n=338/352), mostly for CTX-M-15 (98.9%, n=334/338). Nine participants (1.2%) carried AmpC-producing E. coli that harboured blaDHA-1 or blaCMY-2 genes, and two participants (0.3%) each carried a carbapenem-resistant E. coli that harboured both blaNDM-1 and blaCMY-2. Quinolone-resistant O25b: ST131 E. coli were recovered from six participants (0.8%) and were all CTX-M-15 ESBL-producers. Having a household toilet facility was significantly associated with a reduced risk of intestinal colonization (adjusted odds ratio, 0.71; 95% CI, 0.48-0.99; P-value=0.0095) in multivariate analysis. These findings raise serious public health concerns, and effective control of the spread of antibiotic-resistant bacteria is possible by providing better sanitary conditions for communities.

Role of CTX-M-15 gene in spread of extended-spectrum beta-lactamases among immunocompetent patients in Ghana.

Background: Patients with faecal carriage of extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales serve as reservoirs and sources of dissemination and infection. Objective: This report examined immunocompetent patients for faecal carriage of ESBL-producing Enterobacterales in a district care hospital setting in Ghana. Methods: Between March 2019 and May 2020, cross-sectional sampling was performed to enrol patients and conduct questionnaire-structured interviews for factors that predispose patients to ESBL faecal carriage. Faecal samples from study patients were quantified for ESBL-producing Enterobacterales. The ESBL genes were characterised by polymerase chain reaction and sequencing. Results: The overall proportion of ESBL faecal carriage was 35.5% (n = 38/107). The blaCTX-M gene, mostly CTX-M-15, was detected in 89.5% (n = 34/38) of the ESBL-producing isolates. The other ESBL types included blaSHV (n = 3) and blaOXA (n = 1). The CTX-M-15-positive isolates, when present in a faecal sample compared to the non-ESBL-CTX-M-15 isolates, constituted the predominant faecal Enterobacterales, with significantly higher colony counts than all other enterobacteria in that sample. In multivariate regression, independent risk factors for faecal carriage of ESBL-producing Enterobacterales were hospitalisation in the past year, infections since admission, use of antibiotics in the past 6 weeks, and admission from another hospital. Conclusion: The study found that CTX-M-15-producing isolates were the predominant faecal Enterobacterales, and that further investigations are needed to determine the reasons behind this dominance. What this study adds: The CTX-M-15-producing isolates dominance in this study shows the misuse and abuse of antibiotics in an African medical facility and indicates the potential role of immunity in controlling ESBL spread, which is to be investigated further.

Occurrence of Carbapenemases, Extended-Spectrum Beta-Lactamases and AmpCs among Beta-Lactamase-Producing Gram-Negative Bacteria from Clinical Sources in Accra, Ghana.

Beta-lactamase (ß-lactamase)-producing Gram-negative bacteria (GNB) are of public health concern due to their resistance to routine antimicrobials. We investigated the antimicrobial resistance and occurrence of carbapenemases, extended-spectrum ß-lactamases (ESBLs) and AmpCs among GNB from clinical sources. GNB were identified using matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDITOF-MS). Antimicrobial susceptibility testing was performed via Kirby-Bauer disk diffusion and a microscan autoSCAN system. ß-lactamase genes were determined via multiplex polymerase chain reactions. Of the 181 archived GNB analyzed, Escherichia coli and Klebsiella pneumoniae constituted 46% (n = 83) and 17% (n = 30), respectively. Resistance to ampicillin (51%), third-generation cephalosporins (21%), and ertapenem (21%) was observed among the isolates, with 44% being multi-drug resistant (MDR). ß-lactamase genes such as AmpCs ((blaFOX-M (64%) and blaDHA-M and blaEDC-M (27%)), ESBLs ((blaCTX-M (81%), other ß-lactamase genes blaTEM (73%) and blaSHV (27%)) and carbapenemase ((blaOXA-48 (60%) and blaNDM and blaKPC (40%)) were also detected. One K. pneumoniae co-harbored AmpC (blaFOX-M and blaEBC-M) and carbapenemase (blaKPC and blaOXA-48) genes. blaOXA-48 gene was detected in one carbapenem-resistant Acinetobacter baumannii. Overall, isolates were resistant to a wide range of antimicrobials including last-line treatment options. This underpins the need for continuous surveillance for effective management of infections caused by these pathogens in our settings.

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.

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.

Occurrence and significance of fluoroquinolone-resistant and ESBL-producing Escherichia coli and Klebsiella pneumoniae complex of the rectal flora in Ghanaian patients undergoing prostate biopsy.

Background: Reports suggest that fluoroquinolone (FQ)-resistant and ESBL-producing rectal flora are associated with infectious complications in men undergoing transrectal ultrasound-guided prostate needle biopsy (TRUS-B). Objectives: We investigated the relationship between carriage of FQ-resistant and ESBL-producing Escherichia coli and Klebsiella pneumoniae complex of the rectal flora, and the 30 day incidence rate of post-TRUS-B infectious complications. Methods: From 1 January 2018 to 30 April 2019, rectal swabs of 361 patients were cultured pre-TRUS-B for FQ-resistant and ESBL-producing flora. Patients were followed up for 30 days for infectious complications post-biopsy. Multivariable logistic regression analyses were used to identify risk factors. Results: Overall, 86.4% (n = 312/361) and 62.6% (n = 226/361) of patients carried FQ-resistant and ESBL-producing E. coli and K. pneumoniae complex, respectively. Approximately 60% (n = 289/483) of the FQ-resistant and 66.0% (n = 202/306) of the ESBL-positive isolates exhibited in vitro resistance to the pre-biopsy prophylactic antibiotic regimen of levofloxacin and gentamicin. Amikacin and meropenem were the most effective antibiotics against the MDR rectal E. coli and K. pneumoniae complex (78.7% and 84.3%, respectively). The 30 day incidence rate for post-biopsy infections was 3.1% (n = 11/361), with an overall high probability (96.9%) of staying free of infections within the 30 day period post-TRUS-B. Antibiotic use in the previous 3 months was a risk factor for rectal carriage of FQ-resistant and ESBL-positive isolates. Rectal colonization by ESBL-positive E. coli and K. pneumoniae complex comprised an independent risk factor for post-biopsy infectious complications. Conclusions: The findings suggest that a change in prophylactic antibiotics to a more targeted regimen may be warranted in our institution.

The financial impact of puerperal infections on patients, carers and public hospitals in two regions in Ghana.

BACKGROUND: Puerperal infection (PI) is a known maternal health problem globally. However, there is limited information on its economic impact on patients, carers, and public hospitals in lower-middle-income countries, such as Ghana. METHODS: A prospective case-control study was undertaken in two regional hospitals to analyze the cost of PI. A total of 667 and 559 participants were enrolled in the study at the Greater Accra Regional Hospital (GARH) and the Eastern Regional Hospital (ERH), respectively. Total, average and marginal costs were analyzed between patients with and without PI. RESULTS: Within the study period, the prevalence of PI was 9.1% at ERH and 14.9% at GARH. Overall, patients with PI reported excess length of hospital stay (LOS), corresponding to 46.8% and 33.5% increases in average direct cost at ERH and GARH, respectively, compared with their control groups. In almost all cases, the attributable indirect cost was consistent with productivity loss. CONCLUSION: In both hospitals, patients with PI reported excess LOS and increased direct and indirect costs. The total cost of PI to society, which is the sum of the direct cost, productivity loss, and hospital cost, was higher in Greater Accra than in the Eastern region.

Antimicrobial use in hospitalized patients: a multicentre point prevalence survey across seven hospitals in Ghana.

BACKGROUND: Antimicrobial resistance (AMR) is a public health crisis of global proportions. Data is required to understand the local drivers of antimicrobial resistance and support decision-making processes including implementation of appropriate antimicrobial stewardship strategies. OBJECTIVES: To measure antimicrobial usage in hospitals in Ghana. METHODS: Using the Global Point Prevalence instruments and processes, we conducted point prevalence surveys across AMR surveillance sentinel hospitals in Ghana, between September and December 2019. Hospital records of all inpatients on admission at 0800 hours on a specific day were reviewed for antimicrobial use at the time of the survey. Data on antibiotic use, including indication for use and quality of prescribing were recorded. RESULTS: Overall prevalence of antibiotic use across the sentinel sites was 54.9% (n = 1591/2897), ranging between 48.4% (n = 266/550) and 67.2% (n = 82/122). The highest prevalence of antibiotic use 89.3% (n = 25/28) was observed in adult ICUs. The average number of antibiotics prescribed per patient was 1.7 (n = 1562/2620), with the majority (66%, n = 728/2620) administered via the parenteral route. The five most-commonly used antibiotics were metronidazole (20.6%, n = 541/2620), cefuroxime (12.9%, n = 338/2620), ceftriaxone (11.8%, n = 310/2620), amoxicillin/clavulanic acid (8.8%, n = 231/2620) and ciprofloxacin (7.8%, n = 204/2620). The majority (52.2%; n = 1367/2620) of antibiotics were prescribed to treat an infection, whilst surgical prophylaxis accounted for 26.1% (n = 684/2620). CONCLUSIONS: We observed a high use of antibiotics including metronidazole and cephalosporins at the participating hospitals. Most antibiotics were empirically prescribed, with low use of microbiological cultures. High usage of third-generation cephalosporins especially for community-acquired infections offers an opportunity for antibiotic stewardship interventions.