Prevalence of carbapenem resistance in Acinetobacter baumannii and Pseudomonas aeruginosa in sub-Saharan Africa: A systematic review and meta-analysis

Margaret Toluwalayo Arowolo; Oluwatosin Qawiyy Orababa; Morufat Oluwatosin Olaitan; Bisola Victoria Osibeluwo; Utibeima Udo Essiet; Olajumoke Hanah Batholomew; Oluwaseyi Gbotoluwa Ogunrinde; Oluwaseyi Aminat Lagoke; Jeffrey Difiye Soriwei; Olanrewaju David Ishola; Onyinye Maryann Ezeani; Aminat Oyeronke Onishile; Elizabeth Olumodeji

doi:10.1371/journal.pone.0287762

. 2023 Nov 28;18(11):e0287762. doi: 10.1371/journal.pone.0287762

Prevalence of carbapenem resistance in Acinetobacter baumannii and Pseudomonas aeruginosa in sub-Saharan Africa: A systematic review and meta-analysis

Margaret Toluwalayo Arowolo ^1,^*,^#, Oluwatosin Qawiyy Orababa ^2,^#, Morufat Oluwatosin Olaitan ³, Bisola Victoria Osibeluwo ¹, Utibeima Udo Essiet ¹, Olajumoke Hanah Batholomew ⁴, Oluwaseyi Gbotoluwa Ogunrinde ¹, Oluwaseyi Aminat Lagoke ¹, Jeffrey Difiye Soriwei ⁵, Olanrewaju David Ishola ⁶, Onyinye Maryann Ezeani ¹, Aminat Oyeronke Onishile ⁷, Elizabeth Olumodeji ⁸

Editor: Atef Oreiby⁹

PMCID: PMC10684001 PMID: 38015906

Abstract

Carbapenems are effective drugs against bacterial pathogens and resistance to them is considered a great public health threat, especially in notorious nosocomial pathogens like Acinetobacter baumannii and Pseudomonas aeruginosa. In this study, we aimed to determine the prevalence of carbapenem resistance in A. baumannii and P. aeruginosa infections in Sub-Saharan Africa. Databases (PubMed, Scopus, Web of Science, and African Journal Online) were systematically searched following the Preferred Reporting Items for Systematic review and meta-analysis protocols (PRISMA-P) 2020 statements for articles reporting carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) prevalence between 2012 and 2022. Pooled prevalence was determined with the random effect model and funnel plots were used to determine heterogeneity in R. A total of 47 articles were scanned for eligibility, among which 25 (14 for carbapenem-resistant A. baumannii and 11 for carbapenem-resistant P. aeruginosa) were included in the study after fulfilling the eligibility criteria. The pooled prevalence of CRPA in the present study was estimated at 8% (95% CI; 0.02–0.17; I² = 98%; P <0.01). There was high heterogeneity (Q = 591.71, I² = 98.9%; P<0.0001). In addition, this study’s pooled prevalence of CRAB was estimated at 20% (95% CI; 0.04–0.43; I² = 99%; P <0.01). There was high heterogeneity (Q = 1452.57, I² = 99%; P<0.0001). Also, a funnel plot analysis of the studies showed high degree of heterogeneity. The carbapenemase genes commonly isolated from A. baumannii in this study include bla_OXA23, bla_OXA48, bla_GES., bla_NDM, bla_VIM, bla_OXA24, bla_OXA58, bla_OXA51, bla_SIM-1, bla_OXA40, bla_OXA66, bla_OXA69, bla_OXA91, with bla_OXA23 and bla_VIM being the most common. On the other hand, bla_NDM, bla_VIM, bla_IMP, bla_OXA48, bla_OXA51, bla_SIM-1, bla_OXA181, bla_KPC, bla_OXA23, bla_OXA50 were the commonly isolated carbapenemase genes in P. aeruginosa, among which bla_VIM and bla_NDM genes were the most frequently isolated. Surveillance of drug-resistant pathogens in Sub-Saharan Africa is essential in reducing the region’s disease burden. This study has shown that the region has significantly high multidrug-resistant pathogen prevalence. This is a wake-up call for policymakers to put in place measures to reduce the spread of these critical priority pathogens.

Introduction

Antimicrobial resistance (AMR) is a leading public health threat globally, considerably escalating morbidity, mortality and treatment failure of microbial infections, as well as economic losses to individuals and nations [1]. According to the 2016 Review on Antimicrobial Resistance, AMR would be responsible for 10 million deaths yearly by 2050 with a large amount of these deaths occurring in Sub-Saharan Africa [2]. However, a recent report of almost 5 million deaths linked with AMR in 2019 alone has shown that we will be reaching the 10 million AMR-associated deaths sooner than earlier predicted [3].

Carbapenems are beta-lactam antibiotics with broad-spectrum bactericidal activities against both Gram-positive and negative pathogens [4]. They are often used as last-line drugs against bacterial infections [5]. Unfortunately, bacterial pathogens have developed resistance to this last-resort group of antibiotics through various genetic modifications and production of carbapenem-hydrolysing enzymes [6]. Treatment of infections have become more difficult and expensive, especially against the notorious Gram-negative bacteria, due to resistance to last-line antibiotics.

Acinetobacter baumannii and Pseudomonas aeruginosa are Gram-negative pathogens that belong to the ESKAPE group (an acronym for the group of bacteria, encompassing both Gram-positive and Gram-negative species, made up of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species [7]. These are bacterial pathogens that are notorious for their resistance to clinically relevant antimicrobials. Furthermore, carbapenem-resistant A. baumannii (CRAB) and P. aeruginosa (CRPA) have both been grouped as critical priority pathogens for which there is a need to develop new and effective antimicrobials. These have made the surveillance of these two pathogens a necessity, especially in low-middle-income countries where surveillance is poor. A recent report shows that CRAB and CRPA have mortality rates of 30.5% and 24.5% within 90 days of a positive culture [8]. Moreover, CRAB and CRPA were reported to be responsible for 57,700 and 38,100 deaths globally in 2019 respectively [3].

Sub-Saharan Africa (SSA) is known for having a high burden of infectious diseases which might be linked to the poverty level and poor water, sanitation, and hygiene (WASH) practices in the region [9,10]. The [3] report also showed that Sub-Saharan Africa suffers the highest prevalence of AMR-associated death globally. The scarcity of AMR data from SSA has made it difficult to determine the true risk and burden of AMR infections in the region. Also, a recent study predicting the global prevalence of carbapenemase-producing P. aeruginosa could not include majority of Sub-Saharan African countries in the analysis due to scarcity of data. This further emphasizes the need to surveillance of AMR pathogens in Africa, especially in Sub-Saharan Africa. To the best of our knowledge, there is currently no up-to-date systematic review and meta-analysis that reports the pooled prevalence of carbapenem-resistant P. aeruginosa and A. baumannii in Sub-Saharan Africa. This systematic review is an extensive analysis of the prevalence of carbapenem-resistant A. baumannii with the aim to describe the epidemiology within Sub-Saharan Africa. This study also investigated the prevalence of carbapenemase genes in the region. This would provide insight on the public health risks posed by these priority pathogens and the development of sustainable prevention and control interventions in this region.

Method

Search strategy

This study was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines [11]. Electronic databases (PubMed, Scopus, Web of Science, and African Journal Online) were searched for articles published on carbapenem-resistant A. baumannii and/or P. aeruginosa in sub-Saharan Africa. The last search was on the 31st of July 2022.

Eligibility criteria

This study only included studies published in Sub-Saharan Africa between January 2012 and July 2022. Only studies that reported A. baumannii and/or P. aeruginosa prevalence in humans were considered for the analysis. Studies that reported A. baumannii and/or P. aeruginosa prevalence from countries outside Sub-Saharan Africa were excluded from the analysis. Also, only studies that reported at least one case of carbapenem resistance in A. baumannii and/or P. aeruginosa were included. Only studies published in English or with English translations available were included in the final analysis. Lastly, cross-sectional studies, retrospective, and longitudinal analyses were considered in this analysis. Literature and systematic reviews were excluded from this analysis.

Screening strategy

Articles were first screened based on their titles and abstracts by two independent researchers. Two other researchers then screened eligible articles by reading through their full text, ineligible articles were excluded and the reasons for their exclusion were stated (Fig 1). All disagreements were resolved through discussions. A third researcher confirmed the eligibility of the included studies before including them in the analysis. During extraction, for studies that reported different percentages for imipenem or meropenem, preference was given to meropenem since it has better activity against Gram-negative bacteria [12].

Data extraction and quality appraisal

A data extraction table was created by one reviewer and two other reviewers extracted the following data from the eligible articles; first author, study design, study country, study aim, sample size, sample source, organism prevalence, carbapenem-resistance prevalence, Antimicrobial Susceptibility Testing (AST) method, carbapenem used. All disagreements were resolved through discussions and a fourth reviewer confirmed the extracted data. This step was performed for each of the organisms.

Data analysis

The data extracted was cleaned for any eligibility criterion error, and the meta-analysis was performed using RStudio version 4.2.0. The Carbapenem-resistant A. baumannii (CRAB) and P. aeruginosa (CRPA) pooled prevalence of the present study was analyzed using the random-effect model while subgroup prevalence was considered based on the source of the reported studies. Cochran Q statistics and the I² (inverse variance index) were used to analyze the heterogeneity (low, 0–0.25; fair, 0.25–0.5; moderate, 0.5–0.75; and high, above 0.75). A p-value of <0.01 was considered significant. Publication bias and degree of heterogeneity was examined visually with the use of the funnel plot.

Result

A total of 25 articles (CRAB, 14; CRPA 11) (Fig 2) were included in the final analysis after screening 458 articles from different electronic databases. These articles were from different countries and sub-regions of sub-Saharan Africa. Of the 14 articles analysed for the CRAB, South Africa had 4(28.6%), Sudan and Uganda had 2(14.3%) each, while Ethiopia, Senegal Malawi, Kenya, Nigeria, and Sierra Leone had one each. For the CRPA analysis, Nigeria, Ethiopia, Uganda, and Sudan each had 2 eligible articles included in the final analysis while Malawi, Ghana, and Kenya each had just one eligible article (Tables 1 and 2).

Table 1. Data extraction table for carbapenem-resistant A. baumannii (CRAB) studies.

First author	Year	Study design	Study country	Study aim	Sample size	Sample source	A. baumannii prevalence	Carbapenem-resistant A. baumannii prevalence (%)	AST method	Carbapenem use
[13]	2021	cross-sectional study	Sudan	To assess the phenotypic and genotypic patterns of antimicrobial resistant strains of Acinetobacter baumannii at hospital settings, Khartoum, Sudan	36	Human	36	17 (47%)	Disc diffusion	Imipenem
[14]	2013	cross-sectional	South Africa	To evaluate and optimise multiplex polymerase chain reaction (M-PCR) assays for the rapid differentiation of the four subgroups of the OXA genes and the subgroups of the MBL genes of A. baumannii.	97	Human	97	61 (62.8%)	Vitek 2	Meropenem and Imipenem
[15]	2021	Longitudinal	Ethiopia	To detect and phenotypically characterize carbapenem-resistant Gram negative bacilli from Ethiopian public health institute	1337	Human	36	4 (0.3%)	Simplified carbapenem inactivation method	Meropenem
[16]	2016	cross sectional study	Uganda	To determine the prevalence of carbapenem-resistant P. aeruginosa and A. baumannii at Mulago Hospital in Kampala Uganda, and to establish whether the hospital environment harbours carbapenem-resistant Gram-negative rods	869	Human	29	9 (1.04%)	Disc diffusion	Imipenem
[17]	2015	cross-sectional study	South Africa	To determine the prevalence of β-lactamase genes in multidrug-resistant (MDR) clinical A. baumannii isolates using Multiplex-PCR (M-PCR) assays.	94	Human	94	80 (85.1%)	Vitek 2	Meropenem and Imipenem
[18]	2019	cross sectional study	South Africa	To investigated the 28 genetic determinants of multi-drug resistant A. baumannii (MDRAB) at a teaching hospital in 29 Pretoria, South Africa.	100	Human	100	95 (95%)	Vitek 2	Imipenem and Meropenem
[19]	2012	longitudinal prospective study	Senegal	To identify the presence of A. baumannii carbapenem-resistant encoding genes in natural reservoirs in Senegal, where antibiotic pressure is believed to be low	717	Human	78	6 (0.8%)	Disc diffusion	Imipenem
[20]	2019	cross-sectional	Sudan	To characterize the genotypes and phenotypes associated with carbapenem-resistance in Gram-negative bacilli from patients in Sudan	367	Human	not stated	1 (0.3%)	Disc diffusion	Meropenem
[21]	2022	cross-sectional study	Malawi	To ascertain the antimicrobial resistance in clinical bacterial pathogens from in-patient adults in a tertiary hospital in Malawi	694	Human	26	4 (0.58%)	Disc diffusion	Meropenem
[22]	2021	cross sectional study	Kenya	To understand the antibiotic resistance profiles, genes, sequence types, and distribution of carbapenem-resistant gram from patients in six hospitals across five Kenyan counties.	48	Human	27	27 (56%)	Disc diffusion	Meropenem
[23]	2013	cross sectional study	Nigeria	To report the presence of carbapenem-encoding genes in imipenem-resistant A. baumannii among multidrug-resistant clinical isolates collected from the University College Hospital, Ibadan, south-western Nigeria.	5	Human	3	3 (60%)	Combined disc diffusion test (CDDT)	Imipenem
[24]	2017	cross-sectional	Uganda	To determine the intra-species genotypic diversity among P. aeruginosa and Acinetobacter baumannii isolated from hospitalized patients and the environment at Mulago Hospital	736	Human	7	1 (0.14%)	Disc diffusion	Meropenem
[25]	2020	cross-sectional	Sierra Leone	To assess antibiotic resistance rates from isolates in the urine and sputum samples of patients with clinical features of healthcare-associated infections HAIs.	164	Human	16	2(1.2%)	Vitek 2	Meropenem and Imipenem
[26]	2018	retrospective descriptive study	South Africa	To determine prevalence of culture confirmed sepsis due to A. baumannii, antimicrobial susceptibility and case fatality rates (CFR) due to this organism	93527	Human	399	11 (0.01%)	Disc diffusion	Meropenem and Imipenem

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CRAB = Carbapenem-resistant Acinetobacter baumannii.

AST = Antimicrobial Susceptibility Testing.

*The percentage in the bracket is a fraction of the sample size.

Table 2. Data extraction table for carbapenem-resistant P. aeruginosa (CRPA) studies.

First author	Year	Study design	Study country	Study aim	Sample size	Sample source	P. aeruginosa prevalence	Carbapenem-resistant P. aeruginosa prevalence (%)	AST method	Carbapenem used
[21]	2022	cross sectional	Malawi	To ascertain antimicrobial resistance (AMR) in clinical bacterial pathogens from in-hospital adult patients at a tertiary hospital in Malawi	694	Human	29	18 (2.5%)	Disc diffusion	Meropenem
[15]	2021	cross sectional	Ethiopia	To detect and phenotypically characterise carbapenemase no-susceptible Gram-negative bacilli at the Ethopian Public health institute	1337	Human	36	4(0.2%)	Disc diffusion	Meropenem
[16]	2016	cross sectional	Uganda	To determine the prevalence of carbapenem-resistant P. aeruginosa and A. baumannii at Mulago Hospital in Kampala Uganda, and to establish whether the hospital environment harbours carbapenem-resistant Gram-negative rods	869	Human	42	9 (1.15%)	Disc diffusion	Imipenem
[27]	2019	cross sectional	Nigeria	To investigate the occurrence of MBL-producing bacteria in a healthcare facility in Nigeria.	110	Human	Not reported	13(11.8%)	Combined disc method
[20]	2019	cross sectional	Sudan	To characterise the phenotypes and genotypes associated with carbapenems-resistant in gram-negative bacilli isolated	367	Human	Not reported	14(3.8%)	Disc diffusion	Meropenem
[28]	2019	cross sectional	Ghana	To apply phenotypic and genotypic methods to identify and characterise carbapenem-resistant (CR) Gram-negative bacteria from the hospital environment in Ghana.	111	Human	Not reported	51(45.9%)	Disc synergy	Edoripenem (75%), imipenem (66.7%) and meropenem (58%)
[22]	2021	Cross-sectional	Kenya	To understand the antibiotic resistance profiles, genes, sequence types, and distribution of carbapenem-resistant Gram negative bacteria from patients in six hospitals across five Kenyan counties by bacterial culture, antibiotic susceptibility testing and whole genome sequence analysis. Culture, antibiotic susceptibility testing, and whole-genome sequence analysis.	48	Human	14	14(29.2%)		Meropenem
[29]	2021	cross sectional	Nigeria	To determine the incidence and Molecular Characterization of Carbapenemase Genes in Association with Multidrug-Resistant Clinical Isolates of Pseudomonas aeruginosa from Tertiary Healthcare Facilities in Southwest Nigeria	430	Human	430	71(16.5%)	Disc diffusion	Meropenem and doripenem
[24]	2017	cross sectional	Uganda	To report the intra-species genotypic diversity among P. aeruginosa and A. baumannii isolated from hospitalized patients and the environment at Mulago Hospital, using repetitive elements-based PCR (Rep-PCR) genotyping.	736	Human	9	3(0.4%)		Meropenem
[29]	2018	Cross sectional	Sudan	To detect (blaVIM, blaIMP and blaNDM) Metallo-β-lactamase genes in Khartoum state	200	Human	54	33(16.5%)	Disc diffusion	Meropenem and/ or imipenem.
[30]	2019	Cross sectional	Ethopia	To identify and determine multi-drug resistant, extended spectrum β-lactamase and carbapenemase producing bacterial isolates among blood culture specimens from pediatric patients less than five years of age from Tikur Anbessa Specialized Hospital using an automated BacT/Alert instrument.	340	Human	Not reported	4(1.1%)	Disc diffusion	Meropenem

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CRPA = Carbapenem-resistant Pseudomonas aeruginosa.

AST = Antimicrobial Susceptibility Testing.

*The percentage in the bracket is a fraction of the sample size.

Meta-analysis of Carbapenem-resistant A. baumannii

The pooled prevalence of CRAB in the present study was estimated at 20% (95% Confidence Interval [CI]; 0.04–0.43; I² = 99%; P <0.01) (Fig 3). The funnel plot (Fig 4) and Q statistics show high heterogeneity (Q = 1452.57, I² = 99%; P<0.0001) (S1 Fig) between the CRAB studies.

Meta-analysis of carbapenem-resistant P. aeruginosa

The pooled prevalence of CRPA in the present study was estimated at 8% (95% CI; 0.02–0.17; I² = 98%; P <0.01) (Fig 5). Similarly, there was high heterogeneity between CRPA studies analysed as shown by the Q statistics (Q = 591.71, I² = 98.9%; P<0.0001) and the funnel plot (Figs 6 and S2).

Prevalence of carbapenem-resistant genes in A. baumannii and P. aeruginosa in Sub-Saharan Africa

The carbapenemase genes isolated from A. baumannii reported in the articles analysed include bla_OXA23, bla_OXA48, bla_GES, bla_NDM, bla_VIM, bla_OXA24, bla_OXA58, bla_OXA51, bla_SIM-1, bla_OXA40, bla_OXA66, bla_OXA69, bla_OXA91. The most common carbapenemase gene in the studies analysed are the bla_OXA23 and bla_VIM. On the other hand, the carbapenemase genes reported in P. aeruginosa from studies in Sub-Saharan Africa included in this analysis are bla_NDM, bla_VIM, bla_IMP, bla_OXA48, bla_OXA51, bla_SIM-1, bla_OXA181, bla_KPC, bla_OXA23, bla_OXA50. The most frequent among them are the bla_VIM and bla_NDM genes.

Discussion

Carbapenems are important broad-spectrum antimicrobials of last-resort; hence, resistance to them signifies increased infection mortality, hospital stay duration, and cost of treatment [31]. This challenge is mostly common to infections associated with notorious clinical pathogens such as A. baumannii and P. aeruginosa [32]. These two Gram-negative pathogens have been linked to varieties of hospital-acquired infections and multidrug resistance.

Carbapenemase-resistant A. baumannii in Sub-Saharan Africa in this study was estimated at 20% (95% CI; 0.04–0.43; I² = 99%; P <0.01). [33] in their study on the occurrence and frequency of hospital-acquired (carbapenem-resistant) A. baumannii in Europe (EUR), Eastern Mediterranean (EMR) and Africa (AFR) stated similar results with a pooled incidence of Hospital Acquired-CRAB of 21.4 (95% CI 11.0–41.3) cases per 1,000 patients in the EUR, EMR and AFR WHO regions. On the other hand, our study revealed the pooled prevalence of CRPA in Sub-Saharan Africa to be 8% (95% CI; 0.02–0.17; I² = 98%; P <0.01). This value is relatively low compared to the prevalence of carbapenem resistance reported in Indonesia, India, Italy, China, Germany, and Spain [34]. An additional study from Asia recounted a prevalence of 18.9% CRPA in the Asia-Pacific region. The unexpectedly lower prevalence reported in this study might be due to the absence data from many of the Sub-Saharan African countries. The high heterogeneity observed in this study is most likely not due to publication bias but a result of the different prevalence rates reported in the different studies analysed from different parts of Sub-Saharan Africa and the low number of eligible articles analysed in this study (Figs 5 and 6).

The most common carbapenem-resistant genes in P. aeruginosa in the compared studies in this analysis are the NDM and VIM genes. In the reports of [34] the bla_VIM and bla_IMP were the most prevalent carbapenemase genes in P. aeruginosa in Italy and Indonesia. The dominance of OXA-23 genes in CRAB isolates in many of the studies is not surprising as this gene has been associated with carbapenem resistance in this organism since the 1980s [35]. Furthermore, an earlier study indicated that the existence of plasmid encoding OXA-23 alone in A. baumannii is sufficient to confer resistance to carbapenem in A. baumannii [36]. Even though some of the studies analysed reported carbapenemase genes, many of them did not report the molecular basis of carbapenem resistance in their study. This might be a result of low resources for molecular techniques in many Sub-Saharan African labs.

The pooled prevalence during 2012–2022 should maximally reflect the current status of antibiotic resistance (Tables 1 and 2). Thus, we believe that the current prevalence of antibiotic resistance in A. baumannii infection is similar in the Sub-Saharan countries where these studies were carried out, most of which are facing the same degree of severity of antibiotic resistance. Most published studies have concentrated on the hospital epidemiology of these organisms and animal healthcare settings making it difficult to demonstrate the extra-hospital origin of A. baumannii. Thus, although antibiotic resistance has long been considered as a modern phenomenon, it predates the concept of selective antibiotic pressure due to clinical antibiotic usage [37].

Over the last few decades, the intensive use of antibiotics in humans and as growth-promoting and as prophylactic agents in livestock have resulted in serious environmental and public health problems since this enhances antimicrobial selective pressure [38]. According to a study by [39], it was discovered that A. baumannii isolated from various environmental locations has been linked to nosocomial spread. The resistant bacteria from the extra-hospital environments may be transmitted to humans, to whom they cause diseases that are difficult to treat with conventional antibiotics.

A major strength of our study is that we included studies comprising both in-patients and out-patients and from a range of different samples, which ensured the representativeness of our estimates for these institutions. However, our study has some limitations. Firstly, the country representativeness of the individual studies is unclear in most cases, limiting our findings’ external validity. Secondly, studies are not evenly distributed across the Sub-Saharan regions. Some countries have more studies included in the analysis while there were no studies from others. Consequently, possible differences in CRAB and CRPA incidence and prevalence between the countries may be masked by geographical proximity. Thirdly, due to the relatively low number of hospital-wide studies, our hospital-wide estimates of hospital-acquired A. baumannii infections are unlikely to be generalizable.

Conclusion

Acinetobacter baumannii and Pseudomonas aeruginosa are two important public health pathogens due to their increasingly multidrug-resistant nature. The prevalence of CRAB and CRPA reported in Sub-Saharan Africa indicates a serious threat to the Sub-Saharan African populace. Sensitization on the dangers of self-medication and poor antibiotics stewardship should be intensified as well as advocacy for the reduction in the use of antibiotics for growth promotion and prophylactics in animals. There is a need for urgent and comprehensive surveillance studies including both hospital environments and communities to determine the true prevalence of these drug-resistant pathogens in sub-Saharan Africa. Moreover, finally, infection control policies promoting personal and environmental hygiene, and appropriate administration of antibiotics by clinicians and veterinarians should be made and enforced to facilitate the reduction of CRAB in the region.

Supporting information

S1 Fig. Analysis summary for CRAB.

(PDF)

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S2 Fig. Analysis summary for CRPA.

(PDF)

Click here for additional data file.^{(114.7KB, pdf)}

S1 File

(DOCX)

Click here for additional data file.^{(21.9KB, docx)}

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The authors received no specific funding for this work.

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PLoS One. doi: 10.1371/journal.pone.0287762.r001

Decision Letter 0

Adriano Gianmaria Duse

Transfer Alert

This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present.

12 Dec 2022

PONE-D-22-27050

Prevalence of carbapenem resistance in Acinetobacter baumannii and Pseudomonas aeruginosa in sub-Saharan Africa: a systematic review and meta-analysis

PLOS ONE

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Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: General comments:

1. Absence of page numbers and line numbers.

2. Genus and species are not consistently italicised in the main text.

3. Figures should not be included in the text according to journal recommendations.

4. Spelling errors : ''Acinetobacter baumanii'' for Acinetobacter baumannii'', Discussion - ''tecnics'' for ''techniques'',

table 1 and 2: ''disc'' instead of ''disk''.

5. Word in full prior to using abbreviations: e.g. AST for antimicrobial susceptibility testing.

Abstract:

1. Extra comma after blaimp under results section.

2. Add the funnel plot analysis to the methods.

3. This sentence is not mentioned/explained in the main text ''Carbapenem-resistant A. baumannii prevalence based on

sample source gave estimates of 24% (95% CI; 6 – 49; I2=99%; P<0.01). ''

Introduction:

1. It would be beneficial to mention the global statistics with regards to the prevalence of carbapenem resistant

Acinetobacter baumannii and Pseudomonas aeruginosa here.

2. Prevalence of the common carbapenemase genes worldwide amongst CRAB and CRPA should be highlighted here.

3. Please reword this sentence: ''This has made infection therapy more difficult and expensive, especially against the

notorious Gram-negative bacteria''

4. Define ''ESKAPE group.''

Methods:

1. Need to define the study period accurately and include the months in 2012 and 2022 as the start and end dates.

2. Were all studies that meet the eligibility criteria, irrespective of language, included?

Results:

1. For the carbapenem resistant Pseudomonas aeruginosa (CRPA), a total of 11 articles reviewed, however, only 9 articles

mentioned (1st paragraph).

2. Figure 2, spelling error, ''Ghan'' for ''Ghana''. Only 10 articles instead of 11 mentioned for the CRPA.

3. Please recheck the Table 1: Nogbou et al, study aim - grammatical error.

Olaitan et al, study aim - spelling error (carbapenemase-encoding genes)

Table 2: Abdeta et al, study aim - spelling error ( non-susceptible)

Codejoe et al, eligibility criteria for article selection includes only human isolates of

carbapenem resistant Acinetobacter baumannii (CRAB) and CRPA. This study, however,

reflects the bacterial isolates from the hospital environment. Please recheck for eligibility.

4. Please use a key for wording AST below tables 1 and 2.

5. Please realign the wording in tables 1 and 2 for similarity.

6. Table 1 and table 2, please check and recalculate the % prevalence for the CRAB and CRPA as many are incorrect,

e.g. table 1, CRAB prevalence for Musila et al is written as 56% despite all (27) isolates of Acinetobacter baumannii

being CRAB.

7. Table 2, Pseudomonas aeruginosa prevalence is missing in a few studies.

8. Figure 3 is not clear, very hazy.

9. The interpretation of the funnel plots are not described.

10. Please rewrite this sentence as it is ambiguous: ''Of the 14 articles analysed for the CRAB, (28.6%) were from South

Africa, Sudan and Uganda had 2(14.3%) each, while Ethiopia, Senegal Malawi, Kenya, Nigeria, and Sierra Leone had

one each''.

Discussion:

1. Please combine these sentences: ''Carbapenems are important broad-spectrum antimicrobials of last-resort, hence,

resistance to them signifies increased infection mortality, hospital stay duration, and cost of treatment (Friedman et al.,

2016). More importantly, when the infection is associated with notorious clinical pathogens such as A. baumanii and P.

aeruginosa.''

2.These sentences are redundant, please remove ''The true prevalence of these pathogens in sub-Saharan Africa is not well

known, especially the carbapenem-resistant strains. This study was carried out to determine the prevalence of the

carbapenem-resistant strains of A. baumanii and P. aeruginosa.''

3.This sentence does not make sense, please reword ''Thus, we believe that the current prevalence of antibiotic resistance

in A.baumannii infection is similar to the Sub-Saharan countries where these studies were carried out, most of which are

facing the same degree of severity of antibiotic resistance"'.

4. This sentence is confusing, advise rephrasing: A major strength of our study is that we included studies comprising of

non-disease-specific patients from patients, which ensured the representativeness of our estimates for these

institutions."

Conclusion:

1. Sentence very lengthy, please rewrite/reword: ''Urgent epidemiological studies through comprehensive

surveillance of the pathogen at both hospital and community-based that will showcase the

prevalence of CRAB in the environment, animal/animal products, and the hospital is advocated

to be conducted with the inclusion of sub-Saharan African countries currently lacking this data.''

References:

1. References appear inconsistent. Was a reference manager used?

2. Advise vancouver style of intext referencing preferred by the journal.

Reviewer #2: Dear editor,

Thank you for inviting me to review this manuscript that analyses AMR for these two important organisms.

Comments and suggestions

Abstract

Background:

Introduction

In reference to Global burden of AMR, it would be advisable to mention attributable deaths to bacterial AMR.

Eligibility criteria, enhancement by recent publications.

There are some additional studies on ACIBA in the latest few months should be beneficial to mention, example: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271355;

Results

Heading:

Prevalence of Carbapenem-resistant genes in A. baumanii and P. aeruginosa in sub-

Saharan Africa

Authors listed genes but no numbers or percentages from AST data reported, it would add value to the report.

It is interesting that authors haven’t quoted GLASS surveillance that have ACIBA aggregate data. It would add value to the discussion.

Please pay attention on typos.

END of COMMENTS

**********

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Reviewer #1: No

Reviewer #2: Yes: Olga Perovic

**********

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PLoS One. 2023 Nov 28;18(11):e0287762. doi: 10.1371/journal.pone.0287762.r002

Author response to Decision Letter 0

25 Jan 2023

January 25, 2023

Adriano Gianmaria Duse, MD

Academic Editor

PLOS ONE

Dear Professor Adriano Gianmaria Duse,

Thank you for your reply regarding our manuscript PONE-D-22-27050 titled ‘Prevalence of carbapenem resistance in Acinetobacter baumannii and Pseudomonas aeruginosa in sub-Saharan Africa: a systematic review and meta-analysis.’

We are grateful for you and the reviewers’ comments, and the positive evaluation of our work. We have revised and modified the manuscript to meet PLOS ONE’s style requirements, including those for file naming. We have reconstructed the minor overlapping text with the publication stated in the PLOS ONE decision letter and cited all sources used in this article.

Sincerely,

Margaret Toluwalayo Arowolo

Department of Microbiology

Faculty of Science

University of Lagos

Akoka-Yaba, Lagos

Nigeria

Journal Requirements: All the requirements stated have been revised and have been added to the manuscript.

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

- https://www.tandfonline.com/doi/full/10.1080/22221751.2019.1698273

-https://www.thefreelibrary.com/Prevalence+and+molecular+analysis+of+multidrug-resistant...-a0618470261

We will update your Data Availability statement to reflect the information you provide in your cover letter.

4. Please ensure that you refer to Figures 5, 6 and 7 in your text as, if accepted, production will need this reference to link the reader to the figure.

We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission:

a. You may seek permission from the original copyright holder of Figure 2 to publish the content specifically under the CC BY 4.0 license.

We recommend that you contact the original copyright holder with the Content Permission Form (http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text:

Please upload the completed Content Permission Form or other proof of granted permissions as an "Other" file with your submission.

The following resources for replacing copyrighted map figures may be helpful:

USGS National Map Viewer (public domain): http://viewer.nationalmap.gov/viewer/

The Gateway to Astronaut Photography of Earth (public domain): http://eol.jsc.nasa.gov/sseop/clickmap/

Maps at the CIA (public domain): https://www.cia.gov/library/publications/the-world-factbook/index.html and https://www.cia.gov/library/publications/cia-maps-publications/index.html

NASA Earth Observatory (public domain): http://earthobservatory.nasa.gov/

Landsat: http://landsat.visibleearth.nasa.gov/

USGS EROS (Earth Resources Observatory and Science (EROS) Center) (public domain): http://eros.usgs.gov/#

Natural Earth (public domain): http://www.naturalearthdata.com/

Detailed response: we have addressed your editorial comments and responded to the comments by the reviewers as follows:

Response to Editor only (not for reviewers)

Reviewer #1: General comments:

1. Absence of page numbers and line numbers.- Page numbers and line numbers have been added to the revised manuscript.

2. Genus and species are not consistently italicised in the main text.- This has been corrected

3. Figures should not be included in the text according to journal recommendations.- This has been corrected

4. Spelling errors : ''Acinetobacter baumanii'' for Acinetobacter baumannii'', Discussion - ''tecnics'' for ''techniques'' table 1 and 2: ''disc'' instead of ''disk''.- This has been corrected

5. Word in full prior to using abbreviations: e.g. AST for antimicrobial susceptibility testing.- This has been effected

Abstract:

1. Extra comma after blaimp under results section.- The extra comma has been removed

2. Add the funnel plot analysis to the methods.- This has been added

3. This sentence is not mentioned/explained in the main text ''Carbapenem-resistant A. baumannii prevalence based on

sample source gave estimates of 24% (95% CI; 6 – 49; I2=99%; P<0.01). ''- This has been explained.

Introduction:- These points have been observed and corrected in the revised manuscript

1. It would be beneficial to mention the global statistics with regards to the prevalence of carbapenem resistant

Acinetobacter baumannii and Pseudomonas aeruginosa here.

2. Prevalence of the common carbapenemase genes worldwide amongst CRAB and CRPA should be highlighted here.

3. Please reword this sentence: ''This has made infection therapy more difficult and expensive, especially against the

notorious Gram-negative bacteria''

4. Define ''ESKAPE group.''

Methods: These points have been observed and corrected in the revised manuscript

1. Need to define the study period accurately and include the months in 2012 and 2022 as the start and end dates.

2. Were all studies that meet the eligibility criteria, irrespective of language, included?

Results: These points have been observed and corrected in the revised manuscript

1. For the carbapenem resistant Pseudomonas aeruginosa (CRPA), a total of 11 articles reviewed, however, only 9 articles

mentioned (1st paragraph).

2. Figure 2, spelling error, ''Ghan'' for ''Ghana''. Only 10 articles instead of 11 mentioned for the CRPA.

3. Please recheck the Table 1: Nogbou et al, study aim - grammatical error.

Olaitan et al, study aim - spelling error (carbapenemase-encoding genes)

Table 2: Abdeta et al, study aim - spelling error ( non-susceptible)

Codejoe et al, eligibility criteria for article selection includes only human isolates of

carbapenem resistant Acinetobacter baumannii (CRAB) and CRPA. This study, however,

reflects the bacterial isolates from the hospital environment. Please recheck for eligibility.

4. Please use a key for wording AST below tables 1 and 2.

5. Please realign the wording in tables 1 and 2 for similarity.

6. Table 1 and table 2, please check and recalculate the % prevalence for the CRAB and CRPA as many are incorrect,

e.g. table 1, CRAB prevalence for Musila et al is written as 56% despite all (27) isolates of Acinetobacter baumannii

being CRAB. – The % prevalence of CRAB and CRPA were calculated as a ratio of of the drug-resistant strains to the total sample size x 100.

7. Table 2, Pseudomonas aeruginosa prevalence is missing in a few studies.

8. Figure 3 is not clear, very hazy.

9. The interpretation of the funnel plots are not described.

10. Please rewrite this sentence as it is ambiguous: ''Of the 14 articles analysed for the CRAB, (28.6%) were from South

Africa, Sudan and Uganda had 2(14.3%) each, while Ethiopia, Senegal Malawi, Kenya, Nigeria, and Sierra Leone had

one each''.

Discussion: These points have been observed and corrected in the revised manuscript