Outbreak of Multidrug-resistant Acinetobacter baumannii in a Tertiary Health Center from Northwestern Nigeria.

Background: In spite of its global notoriety and WHO alarm, Acinetobacter baumannii is still an understudied critical-priority pathobiont in Nigeria. We characterized its antimicrobial susceptibility profile and resistance genes during an outbreak. Materials and Methods: This cross-sectional study involved collection of patients' urine samples and swabs from unit staff's hands and ward environments for the identification of A. baumannii strains using standard morphologic and biochemical methods. The disk diffusion method was used to assess the antimicrobial susceptibility profile of the isolates with the production of extended-spectrum beta-lactamases (ESBLs) confirmed by the combined disk test screening method. Characterization of the resistance genes of the ESBL producers was carried out using polymerase chain reaction polymerase chain reaction technique. Results: A.total of eight (six clinical and two nonclinical) A. baumannii isolates were identified. The overall isolate susceptibility and resistance rates to all the antimicrobial agents was 56.3% (27/48) and 35.4% (17/48), respectively. Similarly, all (8/8; 100.00%) isolates were susceptible to meropenem and 75.0% (6/8) to ampicillin-sulbactam while 62.5% (5/8) were resistant to trimethoprim-sulfamethoxazole and 50.0% (4/8) to each of ciprofloxacin and ceftazidime. In addition, 37.5% (3/8) of the isolates were multidrug resistant (MDR) with nonclinical isolates exhibiting more antimicrobial resistance than their clinical counterparts (9/12%-75.0% vs. 8/36%-22.2%). Phenotypic detection and molecular characterization revealed three ESBL-producing isolates that each harbored blaSHV and blaTEM genes with blaCTX-M gene being absent. Conclusion: MDR strains of A. baumannii harboring blaSHV and blaTEM genes were recovered from clinical and environmental sources during the outbreak, which was contained with preventive measures recommended.

Résumé En dépit des alertes faites par l'organisation mondiale de la Santé (OMS), Acinetobacter baumannii demeure un pathobiont sous-étudié et très peu priorisé au Nigeria. Nous avons procedé à sa caractérisation phénotypique et génotypique en dressant son profil de sensibilité aux antimicrobiens et ainsi que les gènes de résistance impliqués au cours d'une épidémie. Matériel et méthodes: Cette étude transversale a consisté à collecter des échantillons d'urine de patients et des écouvillons des mains du personnel des soins et de l'environnement hospitalier. L'identification des souches d' A. baumannii était faite par des méthodes bactériologiques standard. le profil de sensibilité aux antimicrobiens des isolats a été faite par la méthode de diffusion de disque , les bêta-lactamases à spectre étendu (BLSE) étaient recherchée par la méthode de dépistage combinée de disque ainsi que leur caractérisation moléculaire par la mise en évidence des gènes de résistance BLSE à l'aide d'une PCR (réaction en chaîne par polymérase). Résultats: Au total, huit isolats d'A. baumannii (6 cliniques et 2 de l'environnement) ont été identifiés. Les taux globaux de sensibilité et de résistance des isolats à tous les agents antimicrobiens étaient respectivement de 56,3 % (27/48) et de 35,4 % (17/48). De même, tous les isolats (8/8 ; 100,00 %) étaient sensibles au méropénème et 75,0 % (6/8) à l'ampicilline-sulbactam, tandis que 62,5 % (5/8) étaient résistants au triméthoprime-sulfaméthoxazole et 50,0 % (4/8) à la ciprofloxacine et à la ceftazidime. En outre, 37,5 % (3/8) des isolats étaient multirésistants (MDR), les isolats non cliniques présentant une plus grande résistance aux antimicrobiens que leurs homologues cliniques (9/12 %-75,0 % contre 8/36 %-22,2 %). La détection phénotypique et la caractérisation moléculaire ont révélé trois isolats producteurs de BLSE qui hébergeaient chacun les gènes blaSHV et blaTEM, le gène blaCTX-M étant absent. Conclusion: Des souches multirésistantes d'A. baumannii portant les gènes blaSHV et blaTEM ont été identifiées sur des prélevements cliniques et environnementaux au cours de l'épidémie, qui a été gerée grâce aux mesures préventives recommandées. Mots-clés: Surveillance de la résistance aux antimicrobiens, blaSHV carbapénème, pathogène ESKAPE, infections associées aux soins de santé, pratiques de prévention et de contrôle des infections, one health, uropathogènes.

Genomic features of an isolate of Empedobacter falsenii harbouring a novel variant of metallo-ß-lactamase, blaEBR-4 gene.

Empedobacter falsenii is an emerging opportunistic pathogen that has been occasionally implicated in various human infections. In this study, we described the genomic features of a multidrug resistant E. falsenii Q1655 obtained from a patient attending a public hospital in Sokoto, northwest Nigeria. The isolate, E. falsenii Q1655, was isolated from the stool sample of a patient in Sokoto, Nigeria. The identity of the isolate was confirmed by MALDITOF-MS. The disc diffusion test and modified Carba-NP test were used for phenotypic antibiotic susceptibility test and carbapenemase enzyme production test, respectively. The whole genome of the strain was sequenced using the Illumina MiSeq technique. Resistome analysis was done by annotation of the WGS against the ARG-ANNOT database. The isolate was resistant to all ß-lactam antibiotics with the exception of cefepime. The MICs of imipenem and ertapenem as determined by E-test were 12 µg/ml and 2 µg/ml, respectively. Modified Carba NP test showed that the strain was carbapenemase producing. Resistome analysis revealed the presence of a novel metallo-ß-lactamase, a chromosomal blaEBR-4, which exhibited 94.92% and 97.02% nucleotide and protein sequence identities respectively with blaEBR-3 gene of E. falsenii 174,820. Seven and eight amino-acid substitutions were observed with the blaEBR-1 and blaEBR-2, respectively. We reported the first isolation and genomic description of an extensively drug resistant isolate of Empedobacter falsenii in Nigeria. This report broadens our knowledge of carbapenem resistance in E. falsenii and it will serve as a useful guide in the development of antibiotic use policy.

Molecular Characterization of Clinical Carbapenem-Resistant Enterobacteriaceae Isolates from Sétif, Algeria.

This study aimed to determine the incidence and the molecular mechanisms of carbapenem-resistant Enterobacteriaceae in patients from the Sétif University Hospital, Algeria. Nonduplicate clinical bacterial isolates recovered from patients attending the University Hospital of Sétif were collected between April and October 2018. Species identification was performed by MALDI-TOF/MS (matrix-assisted laser desorption ionization-time of flight mass spectrometry) method. The susceptibility of the isolates to carbapenems was determined using the disc diffusion method. The carbapenem resistant isolates were screened for the presence of common carbapenemase genes (blaKPC, blaOXA-48, blaVIM, blaIMP, and blaNDM) and extended-spectrum ß-lactamase (blaCTX, blaTEM, and blaSHV) using PCR and sequencing technique. A total of 123 nonrepetitive Enterobacteriaceae isolates were obtained. Klebsiella pneumoniae (n = 52/42.28%), Escherichia coli (n = 24/19.51%), and Enterobacter cloacae (n = 19/15.45%) were the most prevalent species. The Carba-NP test showed that 6 out of 123 isolates carried carbapenemase enzymes. OXA-48 was found in five isolates (four K. pneumoniae and one E. coli) and NDM-5 in one E. cloacae isolate. We reported for the first time in Algeria the presence of NDM-5 carbapenemase enzyme in a clinical E. cloacae isolate.

Bhargavaea massiliensis sp. nov. and Dietzia massiliensis sp. nov., Novel Bacteria Species Isolated from Human Urine Samples in Nigeria.

Two novel bacteria species designated Marseille-Q1000T and Marseille-Q0999T were isolated from urine samples of patients in Sokoto, Northwest-Nigeria. They were Gram-positive bacteria and belong to two different genera, Bhargavaea and Dietzia. The genome size and G + C content of Marseille-Q1000T and Marseille-Q0999T were 3.07 and 3.51 Mbp with 53.8 and 71.0 mol% G + C content, respectively. The strains exhibited unique phenotypic and genomic features that are substantially different from previously known bacterial species with standing in nomenclature. On the basis of the phenotypic, phylogenetic and genomic characteristics, strains Marseille-Q0999T (= CSURQ0999 = DSM 112394) and Marseille-Q1000T (= CSURQ1000 = DSM 112384) were proposed as the type strains of Bhargavaea massiliensis sp. nov., and Dietzia massiliensis sp. nov., respectively.

Repurposing of antibiotics for clinical management of COVID-19: a narrative review.

BACKGROUND: Drug repurposing otherwise known as drug repositioning or drug re-profiling is a time-tested approach in drug discovery through which new medical uses are being established for already known drugs. Antibiotics are among the pharmacological agents being investigated for potential anti-SARS-COV-2 activities. The antibiotics are used either to resolve bacterial infections co-existing with COVID-19 infections or exploitation of their potential antiviral activities. Herein, we aimed to review the various antibiotics that have been repositioned for the management of COVID-19. METHODS: This literature review was conducted from a methodical search on PubMed and Web of Science regarding antibiotics used in patients with COVID-19 up to July 5, 2020. RESULTS: Macrolide and specifically azithromycin is the most common antibiotic used in the clinical management of COVID-19. The other antibiotics used in COVID-19 includes teicoplanin, clarithromycin, doxycycline, tetracyclines, levofloxacin, moxifloxacin, ciprofloxacin, and cefuroxime. In patients with COVID-19, antibiotics are used for their immune-modulating, anti-inflammatory, and antiviral properties. The precise antiviral mechanism of most of these antibiotics has not been determined. Moreover, the use of some of these antibiotics against SARS-CoV-2 infection remains highly controversial and not widely accepted. CONCLUSION: The heavy use of antibiotics during the COVID-19 pandemic would likely worsen antibiotic resistance crisis. Consequently, antibiotic stewardship should be strengthened in order to prevent the impacts of COVID-19 on the antibiotic resistance crisis.

First whole genome sequence of Paenalcaligenes suwonensis bearing blaVIM-5 Metallo-ß-lactamase: A clinical isolate responsible for acute gastroenteritis.

Carbapenemase-producing Alcaligenes species has been described in only few studies, with none so far from the African continent. Here, we report the whole genome sequence of Peanalcaligenes suwonensis bearing blaVIM-5 metallo-ß-lactamase and first detection of carbapenemase producing Alcaligenes faecalis isolated from patients attending tertiary healthcare facilities in Nigeria. The isolates were identified by MALDI-TOF Mass Spectrometry. Antibiotic susceptibility assay, modified Carba NP test and genomic investigation revealed that two isolates of Alcaligenes faecalis and an isolate of Paenalcaligenes suwonensis harboured blaVIM-5 gene. The genome sequence analysis of the P. suwonensis 191B isolate, responsible for acute gastroenteritis, reveal the presence of 18 antibiotic resistance genes coding for resistance to five different classes of antibiotics. Three of the genes (blaOXA-368, blaCARB-4 and blaVIM-5) codes for resistance to ß-lactam antibiotics. To our best knowledge, we describe here the first genome sequence of P. suwonensis species and the first detection of class B carbapenemase blaVIM-5 in a clinical isolate of P. suwonensis species and Alcaligenes faecalis in Nigeria. The finding of this study is of concern, as lateral dissemination of the genes into clinically important Gram-negative pathogens is highly likely.

Chemical Composition and Antibacterial Activity of Essential Oils from the Algerian Endemic Origanum glandulosum Desf. against Multidrug-Resistant Uropathogenic E. coli Isolates.

Antibiotics are becoming ineffective against resistant bacteria. The use of essential oils (EOs) may constitute an alternative solution to fight against multidrug-resistant bacteria. This study aims to determine the chemical composition of EOs from five populations of the endemic Algerian Origanum glandulosum Desf. and to investigate their potential antibacterial activity against multidrug-resistant uropathogenic E. coli strains. The EOs were obtained by hydrodistillation and their composition was investigated by gas chromatography/mass spectrometry (GC/MS). The antibacterial activity was evaluated by the disc diffusion method against eight E. coli strains (six uropathogenic resistant and two referenced susceptible strains). Minimum inhibitory and bactericidal concentrations (MIC/MBC) were obtained by the broth microdilution method. The main EO components were thymol (15.2-56.4%), carvacrol (2.8-59.6%), γ-terpinene (9.9-21.8%) and p-cymene (8.5-13.9%). The antibacterial tests showed that all the EOs were active against all the strains, including the multidrug-resistant strains. The EO from the Bordj location, which contained the highest amount of carvacrol (59.6%), showed the highest antibacterial activity (inhibition diameters from 12 to 24.5 mm at a dilution of 1/10). To our knowledge, this is the first description of the activity of O. glandulosum EOs against resistant uropathogenic strains. Our study suggests that O. glandulosum EO could be used in some clinical situations to treat or prevent infections (e.g., urinary tract infections) with multidrug-resistant strains.

High prevalence of multidrug-resistant Gram-negative bacterial infections in Northwest Nigeria.

INTRODUCTION: There is limited data on the prevalence and antibiotic susceptibility profile of Gram-negative bacteria in northwest Nigeria. This study thus aimed to investigate the prevalence of multidrug resistant Gram-negative bacterial infections among patients in two healthcare facilities in Sokoto, northwest Nigeria. METHODS: A total of 735 non-duplicate clinical bacterial isolates were collected between January and July 2019, from among specimens processed by the diagnostic microbiological laboratory of the two hospitals. The isolates were identified using MALDI-TOF mass spectrometry and tested against a panel of sixteen (16) antibiotics using the current EUCAST guidelines. RESULTS: Of the 735 randomly selected bacterial isolates, 397 (54.0%) yielded Gram-negative bacteria. In the two hospitals, E. coli 104 (26.2%) and Klebsiella spp. 58 (14.6%) were the most common Gram-negative pathogens implicated in all infections. Overall, the isolates exhibited moderate to high resistance to all tested antibiotics, the lowest was observed against amikacin (7.1%). The phenotypic test for ESBL and carbapenemase enzymes showed that 48 (24.6%) and 15 (32.6%) of the isolates were positive, with 88.9% of the isolates being multidrug resistant. CONCLUSIONS: The study documents prevalent high multidrug resistant Gram-negative bacterial infections, predominantly caused by E. coli and K. pneumoniae in Sokoto, northwest Nigeria. The isolates were mostly MDR and exhibited ESBL and carbapenemase activities. The findings of this study call for urgent implementation of infection control measures and antibiotic stewardship in our hospitals so as to limit the spread of antibiotic-resistant bacteria in our healthcare facilities.

Molecular mechanisms of colistin resistance in Africa: A systematic review of literature.

INTRODUCTION: Updated and comprehensive data on the mechanism underlying colistin resistance is lacking in Africa. LITERATURE SEARCH: Herein, we aimed to review available literature on the molecular mechanisms of colistin resistance in Africa. PubMed, Google Scholar, and African Journal online databases were searched on the 15th of January 2020 for original research articles that reported mechanisms of colistin resistance in any of the 54 African countries. REVIEW: Of the 1473 studies identified through initial database search, 36 met the inclusion criteria. Colistin resistance was mostly observed in Escherichia coli isolated from human clinical samples. Plasmid-mediated colistin resistance mechanism (26; 72.2%) was the most frequently reported resistance mechanism. About three-quarters (27; 75.0%) of the 36 studies were done in North Africa. In this zone, the mobilized colistin resistance (mcr) genes were mostly detected in E. coli harboring three plasmid types, IncHI2, IncI2, and IncX4, from animal samples (n=9; 42.8%). Of the six studies performed in Southern Africa, four reported mcr-1 mostly detected from human samples (n=2; 50.0%) in E. coli isolates carrying IncHI2, IncI2, and IncX4 with diverse range of STs. One hitherto unknown mutation, the mutation in the I527N gene was detected in colistin resistant isolates in this region, which was absent in colistin susceptible isolates. In West and Central Africa, two and one studies, respectively, reported mcr-1 gene exclusively in Escherichia coli isolates. CONCLUSIONS: Transferable plasmid mediated colistin resistance is rapidly emerging in Africa with mcr-1 as the predominant genetic variant in human, animals, and environmental samples.

Global trends and current status in colistin resistance research: a bibliometric analysis (1973-2019).

Background: Colistin resistance is a major breach in our last line of defense and without urgent action, we are heading for a post-antibiotic era, in which common infections and minor injuries can once again kill. To the best of our knowledge, the use of the bibliometric analytical technique for examining colistin resistance-related research does not exist in the literature. Methods: Here, we analyze and present bibliometric indicators of the global literature in colistin resistance research. The Scopus database was searched for articles on colistin resistance. The articles retrieved were analyzed using the bibliometrix R-package. Results: A total of 1105 publications were retrieved. There was a noticeable increase in the number of publications on colistin resistance research in the past decade. Six journals made up the core zone in colistin research and produced 35.83% of the published articles. The analysis across time-intervals revealed several keywords that had increased or decreased in usage when comparing the interval between 1973-2009 and 2010-2019. Authors' keywords "Acinetobacter baumanii", and " Pseudomonas aeruginosa" were the most frequent encountered during the period of 1973-2009, while " mcr-1", " Enterobacteriaceae", " Escherichia coli", and " Klebsiella pneumoniae" emerged in the past decade. Conclusions: There has been a significant growth in publications on colistin resistance in the past decade, suggesting an urgent need for action by different stakeholders to contain this threat of colistin resistance. Keyword analysis revealed temporal changes in the types of keywords used across time-intervals. These findings summarize a general vision on colistin resistance research and will serve as baseline data for future comparative purposes.

Epidemiology of surgical site infections in Nigeria: A systematic review and meta-analysis.

INTRODUCTION: Surgical site infection (SSI) is a major patient safety concern in hospitals. Unlike most developed countries, Nigeria does not yet have an established national system to monitor the occurrence of this infection. This meta-analysis was thus designed to determine the pooled cumulative incidence of SSIs and various determinants of its occurrence in Nigeria. METHODS: The electronic databases were systematically searched for articles reporting the occurrence and risk factors associated with SSIs in Nigeria from January 2000 to December 2018. The eligible articles were evaluated using a set of pre-defined criteria. The extracted data were analysed using the comprehensive meta-analysis software. The Begg and Egger's regression tests were used to assess the risk of bias of the included publications. RESULTS: Thirty-two articles emanating from the six geopolitical regions of Nigeria were included in this meta-analysis. The pooled cumulative incidence of SSIs was 14.5% (95% confidence interval [CI]: 0.113-0.184) with the highest incidence reported in the north-eastern region (27.3%, 95% CI: 0.132-0.481) of the country. It was also found to occur more predominantly following colorectal and abdominal surgeries, among elderly patients and in patients with co-morbid conditions. The most frequently reported was the superficial incisional SSIs occurring in 62.5% (95% CI: 0.333-0.848). Higher preponderance was also observed among patients with dirty wounds (52.7%, 95% CI: 0.367-0.682). CONCLUSION: This meta-analysis documents for the first time the national burden of SSIs in Nigeria. Control measures geared towards its reduction should be strengthened and a national policy on SSI surveillance, prevention and control developed.

Surgical antimicrobial prophylaxis and its dose appropriateness among paediatric patients in a Nigerian teaching hospital.

Surgical antimicrobial prophylaxis (SAP) prevents incision site infection. We assessed SAP compliance with existing international guidelines, evaluated the appropriateness of the antimicrobial doses, and determined the risk factors for antimicrobial under-dosing. A retrospective chart review was performed for patients who under-went surgery and administered antimicrobial prophylaxis. Compliance with SAP guidelines was evaluated. Antimicrobial doses were categorized as under-, normal-, or over-dose. Of the 303 surgical patients, 97.7% received SAP and complete compliance was achieved in 5.6%. Of the 550 antimicrobial prescriptions, metronidazole (42.7%) and cefuroxime (34.7%) were the most prescribed. Over- (31.5%), under- (44.5%), and normal- dosing (24.0%) were recorded, respectively. None of the factors evaluated predicted the risk of antimicrobial under-dosing. Full compliance with international SAP guidelines was poor in our study. Correct timing, re-dosing, and duration of antimicrobial use were the most violated. Most antimicrobials were under-dosed, suggesting a need for national and institutional SAP guidelines.

Occurrence of Surgical Site Infections at a Tertiary Healthcare Facility in Abuja, Nigeria: A Prospective Observational Study.

Surgical site infection (SSI) is one of the most frequent complications of surgical interventions. Several factors have been identified as major determinants of occurrence of SSIs. The present study determined the occurrence and possible risk factors associated with SSIs at a tertiary healthcare facility in Abuja, Nigeria. All patients scheduled for operation in the hospital during the study period and who consented to participate willingly in the study were observed prospectively for the occurrence of SSI based on criteria stipulated by the United States Centre for Disease Control and Prevention (CDC). Data on sociodemographic characteristics, lifestyle, surgical procedure and co-morbidity were collected into a pre-tested data collection tool and analysed using IBM SPSS Statistics software v.24. Predictors of SSIs were identified using multivariate logistic regression model and p-value less than 0.05 was considered statistically significant. Of the 127 surgical patients that met the inclusion criteria comprising 65 (51.2%) females and 62 (48.8%) males between 1 and 83 years with mean age of 25.64 ± 1.66 years, 35 (27.56%; 95% Confidence Interval (CI): 0.205⁻0.360) developed SSIs. Prolonged post-operative hospital stays (p < 0.05), class of wound (p < 0.0001) and some comorbid conditions were found to be significantly associated with higher SSI rate. The SSI rate was highest among patients that had Kirschner-wire insertion (75.0%), followed by an unexpectedly high infection rate among patients that had mastectomy (42.9%), while lower percentages (33.3%) were recorded among patients that had exploratory laparotomy and appendicectomy. The overall magnitude of SSIs in this facility is high (27.6%; 95% CI: 0.205⁻0.360). Several factors were found to be independent predictors of occurrence of SSI. The findings thus highlight the need for improved surveillance of SSIs and review of infection control policies of the hospital.

Molecular characterisation of extended-spectrum ß-lactamase-producing Gram-negative bacterial isolates from surgical wounds of patients at a hospital in North Central Nigeria.

OBJECTIVES: This study aimed to characterise extended-spectrum ß-lactamase (ESBL)-producing Gram-negative bacterial isolates from patients with surgical site infections (SSIs) at a tertiary healthcare facility in Abuja, Nigeria. METHODS: Consecutive, non-duplicate wound swabs were collected over a 3-month period from wounds of patients with SSI and were cultured appropriately. Bacterial isolates were identified using rapid identification kits. The modified agar disk diffusion method was used for antimicrobial susceptibility testing, and phenotypic ESBL activity of the isolates was determined using the double-disk synergy test (DDST). PCR was thereafter used for molecular characterisation of the isolates. RESULTS: A total of 57.1% (20/35) of the bacterial isolates were Gram-negative, with Pseudomonas aeruginosa (7/20; 35.0%) being the most prevalent. The isolates exhibited varying degree of antimicrobial resistance, with resistance as high as 100% for ampicillin and amoxicillin. Phenotypic ESBL production was observed in 65.0% (13/20) of the Gram-negative bacterial isolates. DNA analysis revealed that 61.5%, 53.8% and 38.5% of the isolates harboured blaSHV, blaCTX-M and blaTEM genes, respectively, with 30.8% of the isolates co-harbouring blaSHV and blaCTX-M. Similarly, 23.1% of the isolates harboured blaSHV and blaTEM, whilst 15.4% harboured blaCTX-M and blaTEM. However, none of the investigated isolates harboured a blaOXA gene. CONCLUSION: The prevalence of ESBL genes among Gram-negative SSI pathogens is high. This calls for an urgent need to review infection control policies and antimicrobial prescription patterns as well as increased surveillance of ESBLs as the possibility of an epidemic outbreak of multidrug-resistant pathogens in the hospital is high.