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 Table of Contents  
Year : 2021  |  Volume : 24  |  Issue : 1  |  Page : 1-9

Carbapenem-resistant Enterobacteriaceae infections among patients admitted to intensive care units in Kano, Nigeria

1 Department of Medical Microbiology and Parasitology, Bayero University/Aminu Kano Teaching Hospital, Kano, Nigeria
2 Department of Community Medicine, Bayero University/Aminu Kano Teaching Hospital, Kano, Nigeria
3 Department of Medical Microbiology, Usmanu Danfodio University/Teaching Hospital, Sokoto, Nigeria
4 Department of Global Health, Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, Cape Town, South Africa
5 Department of Medical Microbiology, Ahmadu Bello University, Zaria, Nigeria
6 Multi-drug Resistant Tuberculosis Unit, Infectious Diseases Hospital, Kano, Nigeria
7 Department of Medical Microbiology, Aminu Kano Teaching Hospital, Kano, Nigeria
8 Department of Anaesthesiology and Intensive Care, Bayero University/Aminu Kano Teaching Hospital, Kano, Nigeria
9 Department of Medical Microbiology, University of Maiduguri/University of Maiduguri Teaching Hospital, Maiduguri, Borno State, Nigeria

Date of Submission03-Mar-2020
Date of Decision10-May-2020
Date of Acceptance27-May-2020
Date of Web Publication31-Mar-2021

Correspondence Address:
Dr. Rabiu Ibrahim Jalo
Department of Community Medicine, Bayero University/Aminu Kano Teaching Hospital, Kano
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DOI: 10.4103/smj.smj_14_20

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Background: Globally, intensive care units (ICUs) are encountering emergence and spread of antibiotic-resistant pathogens, and for some pathogens, there are few therapeutic options available. Objectives: The study assessed prevalence, susceptibility pattern, and risk factors of carbapenem-resistant Enterobacteriaceae (CRE) infections among ICU patients in Kano, Nigeria. Materials and Methods: A descriptive cross-sectional study was used to study 190 patients admitted to the ICUs of two tertiary hospitals in Kano. Antibiotic susceptibility of isolated organisms was determined by disc diffusion technique. Suspected carbapenemase producers were further subjected to the modified Hodge test (MHT) method for confirmation. Results: A total of 76 out of the 190 samples yielded clinical isolates of Enterobacteriaceae as follows: 34 (44.7%) Escherichia coli, 19 (25%) Klebsiella pneumoniae, 3 (3.9%) Proteus mirabilis, 4 (5.3%) Enterobacter aerogenes, 3 (3.9%) Proteus vulgaris, 2 (2.6%) Citrobacter freundii, 2 (2.6%) Klebsiella ozaenae, 2 (2.6%) Klebsiella oxytoca, 2 (2.6%) Salmonella subsp. 3b, 2 (2.6%) Enterobacter agglomerans, 2 (2.6%) Enterobacter cloacae, and 1 (1.3%) Serratia odorifera. Screening the Enterobacteriaceae-positive samples for carbapenem resistance using ertapenem disc (10 μg) showed 8 samples (10.5%) as resistant while MHT gave a carbapenem resistance prevalence of 7.9% (6 out of 76). Based on multiplex polymerase chain reaction; the distributions of genotypes of the carbapenemase producers were as follows: Verona Integron Metallo-beta-lactamase (VIM) genes only (4 [50%]) New Delhi Metallo-beta-lactamase (NDM) genes only (2 [25%]), and 1 (12.5%) had Klebsiella pneumoniae carbapenemase (KPC) and VIM gene coexisting. Surgical procedure (P = 0.009) and history of recent admission (P = 0.001) were found to be risk factors for CRE. Conclusion: The study provided evidence of the presence of CRE infections among patients admitted to ICUs in the study centers. This underscores the need for effective infection prevention and control measures to avoid the spread of CRE in hospital setting.

Keywords: Carbapenem, Enterobacteriaceae, intensive care unit, Kano, resistance

How to cite this article:
Aminu A, Daneji IM, Yusuf MA, Jalo RI, Tsiga-Ahmed FI, Yahaya M, Adamu AA, Yaqub Y, Dayyab FM, Edwin CP, Garba S, Gadzama GB. Carbapenem-resistant Enterobacteriaceae infections among patients admitted to intensive care units in Kano, Nigeria. Sahel Med J 2021;24:1-9

How to cite this URL:
Aminu A, Daneji IM, Yusuf MA, Jalo RI, Tsiga-Ahmed FI, Yahaya M, Adamu AA, Yaqub Y, Dayyab FM, Edwin CP, Garba S, Gadzama GB. Carbapenem-resistant Enterobacteriaceae infections among patients admitted to intensive care units in Kano, Nigeria. Sahel Med J [serial online] 2021 [cited 2021 Jun 19];24:1-9. Available from: https://www.smjonline.org/text.asp?2021/24/1/1/312735

  Introduction Top

Antibiotics are antimicrobial agents that are widely used to treat bacterial diseases or for prophylaxis in clinical setting. However, in recent times, there has been a growing global concern about the rate at which microorganisms are becoming resistant to existing antibiotics. The World Health Organization now regards antibiotic resistance as one of the biggest threats to global health.[1] Globally, about 700,000 deaths are attributed to drug-resistant infections yearly, and this is estimated to reach 10 million by 2050.[2] In a review of antimicrobial resistance in Africa, it was reported that resistance to commonly used antibiotics such as fluoroquinolones, tetracyclines, and penicillins among others was already widespread.[3] In addition, carbapenem resistance in Acinetobacter spp. and Pseudomonas aeruginosa was found, although there was a paucity of publications on carbapenem resistance in Enterobacteriaceae.[3]

Carbapenem-resistant Enterobacteriaceae (CRE) are Enterobacteriaceae that are resistant to one or all of the following carbapenems: ertapenem, meropenem, imipenem, or doripenem and resistant to all of the following third-generation cephalosporins: ceftriaxone, cefotaxime, and ceftazidime.[4] CRE are associated with high mortality and morbidity, and death rates of up to 40%–50% have been reported.[4] CRE also carry genes that confer high levels of resistance to many other antimicrobials, which limits therapeutic options. [4],[5] Some of the risk factors for acquiring these CRE include organ or stem cell transplantation, intensive care unit (ICU) admission, poor nutritional status, severe illness, mechanical ventilation, prolonged hospitalization, and previous surgery. [6],[7]

Carbapenems are usually considered the agents of last resort in the treatment of severe infections caused by resistant Gram-negative bacteria, especially those that are resistant to other beta-lactam antibiotics.[8] Resistance to carbapenems is, therefore, a major threat for the treatment of these infections, and production of carbapenemases is the most important molecular mechanism, both epidemiologically and clinically.[8] Carbapenemases in Enterobacteriaceae are represented by three molecular classes of beta-lactamases: A, B, and D.[8],[9],[10] Infections caused by these organisms are increasing in health-care settings, and this poses a serious challenge to clinicians who decide on treatment options and infection prevention specialists in implementing effective infection control interventions.[8]

The burden of CRE in health-care systems varies substantially from country to country. [11],[12] In the United States, 0.08% of Enterobacteriaceae reported from 300 laboratories participating in the Surveillance Network (USA) database were identified as CRE.[9] In another study in India, the CRE prevalence rate was as high as 12.26% and majority of the isolates were detected in urine samples 465 (46%).[4] However, in a general hospital in Egypt out of 54 suspected Enterobacteriaceae isolates, only 0.74% were found to produce carbapenemase.[10] Yet, in another study conducted in northeastern Nigeria, 12.4% of the 225 clinical isolates of Enterobacteriaceae were found to be carbapenemase producers.[6] These variations may be attributable to differences in the environment, standard of personal hygiene, and hospital antibiotic policy and standard treatment guidelines.

Single polymerase chain reaction (PCR) and multiplex PCR are commercially available molecular method tests with high sensitivity and specificity. When followed by sequencing (if necessary), these methods represent the gold standard for specification and identification of carbapenemase gene.[13] Tigecycline, colistin, polymyxins, and intravenous fosfomycin are the treatment options for CRE, but unfortunately, these are not available in most African countries including Nigeria.[14]

CRE compromise effective therapy, and a common problem in endemic settings or during outbreaks is that therapeutic options become limited and are not always optimal.[8],[10],[11],[15] Consequently, the appropriate selection of the initial antibiotic therapy before susceptibility tests are available is difficult. [11],[15] Thus, patients under these conditions have poorer clinical outcomes, the death rates associated with Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria are higher than 50%, while rates associated with metallo-beta-lactamase producers range from 18% to 67%.[11]

The emergence of carbapenemase-resistant bacteria is a global health threat, implicating an extremely high cost for patients and hospitals. [11],[12] This cost is associated with prolonged hospital stays, higher health-care expenses, and increased morbidity, particularly when a second antibiotic is needed for better treatment. [8],[11] The actual cost of controlling infection has been associated with several factors, such as new antimicrobial development (estimated at U$ 1 billion per drug), the need for increased surveillance within each hospital to determine problematic pathogens, and enforced isolation procedures to control spread.[11] Another challenge is inadequate clinical laboratory facilities to give accurate laboratory data for informed choice of therapy. [11],[16] Fast and accurate detection of carbapenem resistance is crucial for guiding the treatment of individual patients as well as for instituting proper infection control measures to limit the spread of the organism.[13] Infection due to CRE is more likely to result in the death of a patient compared with infection due to carbapenem susceptible Enterobacteriaceae.[5] Infections caused by carbapenemase-producing Enterobacteriaceae are increasing worldwide, especially in ICUs, and have been associated with high mortality rates. [17],[18] Carbapenem-resistant organisms are common in German ICUs, and the relatively large proportions of ICU-acquired infections emphasize their potential to cause outbreaks.[19]

Over the past decade, CRE have become one of the most challenging pathogens in infectious diseases. However, the extent to which the burden of carbapenemase-producing Enterobacteriaceae has been described in Nigeria is limited. In this study, we aimed to contribute to this knowledge gap by examining the prevalence of carbapenemase-producing Enterobacteriaceae in ICU patients of selected hospitals in Kano, Nigeria, including their susceptibility pattern and risk factors. The evidence from this study will be useful for clinicians, infection control experts as well as hospital ward managers involved in planning antibiotic stewardship programs.

  Materials and Methods Top

Study design

The study was descriptive cross sectional in design.

Study setting

The study was conducted in Kano State, Nigeria. The state is located in the northwestern zone of Nigeria and is a cosmopolitan city with a population of 13,377,462 million people (projected from 2006 national census (9,401,288), using the estimated growth rate of 2.8%). The inhabitants are of varying occupations and include civil servants, farmers, petty traders, students, and artisans. There are many health facilities in the state, and two of these hospitals – Aminu Kano Teaching Hospital and Muhammad Abdullahi Wase Specialist Hospital – have designated ICUs. Each of these ICUs is four bedded and is used for both adults and children.

Study population

The study population comprised all patients admitted to the ICUs of the selected tertiary hospitals with invasive bacterial diseases (bloodstream infections, catheter-related infections, ventilator-associated infections, etc.) irrespective of age, sex, and clinical condition. Data were collected between January and December 2018.

Exclusion criterion

Patients or caregivers/relatives who refused to give consent to participate in the study were excluded from the study.

Sample size determination

Sample size was calculated using Fisher's formula[20] for determining minimum sample size for descriptive studies (n = Z2pq/d2), based on standard normal (Z) deviate of 1.96 at 95% confidence interval and prevalence rate of 12.8% reported from previous similar study.[21] Possible nonresponse of 10% was factored into the estimated sample size.[22] Hence, an estimated sample size of 191 was obtained.

Ethical considerations

The protocol for this study was submitted to the Health Research Ethics Committee of Aminu Kano Teaching Hospital, Kano, Nigeria, for review and approval before the commencement of data collection. Ethical approval with reference number (NHREC/21/08/12A/P-3/1877) was obtained. Information about the study was provided to the participants or their caregivers/relatives in plain language. After explaining, they were requested to ask questions on any aspect of the study that was not clear to them. They were informed that their participation was voluntary, and they could leave the study at any time they so wished or decline to respond to any question or provide any specimen. Informed written consent was obtained from all the patients who participated in the study.

Sampling method and data collection

All eligible patients admitted to the ICUs of the selected tertiary hospitals were included until the required sample size was attained.

The information was obtained from both the patients and their caregivers/relatives (where appropriate). The following specimens were collected from patients as appropriate: blood, urine, sputum, tracheal aspirate, and swabs. All specimens collected were transported according to standard methods.[6]

Antibiotic susceptibility testing by disc diffusion methods

All identified Enterobacteriaceae were subjected to in vitro susceptibility testing using Kirby–Bauer techniques, as described in Clinical and Laboratory Standards Institute (CLSI) guidelines, and outcome was subsequently interpreted accordingly. The antibiotics tested were ampicillin (10 μg), ceftriaxone (30 μg), aztreonam (30 μg), gentamicin (10 μg), ciprofloxacin (5 μg), and chloramphenicol (30 μg) by disc diffusion method (using commercially available Oxoid, Basingstoke, England).  Escherichia More Details coli ATCC 25922 was used as control strains for the study. [6],[23]

Carbapenem-resistant Enterobacteriaceae screening test

All the bacterial isolates were screened for carbapenemases according to the CLSI guidelines. Ertapenem and meropenem discs (10 μg, Oxoid, Basingstoke, England) were used. The antibiotic discs were placed on the surface of inoculated Mueller-Hinton agar plates using sterile forceps. The discs were placed about 30 mm apart, and the plates were incubated for 24 h at 37°C after which zones of inhibitions were read. Isolates with zone of inhibition ≤21 mm in diameter for meropenem and/or ertapenem were considered as suspected carbapenemase producers. E. coli ATCC 25922 was used as a quality control strain. All Enterobacteriaceae isolates found resistant to meropenem (10 μg) disc and/or ertapenem (10 μg) disc were subjected to confirmatory testing using the modified Hodge test (MHT).

Modified Hodge test

All Enterobacteriaceae isolates resistant to meropenem (10 μg) disc and/or ertapenem (10 μg) disc were subjected to confirmatory testing using the MHT. A 0.5 McFarland standard of E. coli ATCC® 25922 was inoculated in saline and diluted to 1:10 in saline. This suspension was then evenly inoculated with a sterile cotton swab on surface of Mueller-Hinton agar plate. A disc of ertapenem (10 μg, Oxoid, Basingstoke, England) was placed on the surface of Mueller-Hinton agar plate at the center. Thereafter, by means of a sterilized wire loop, the test organism was streaked together with the two quality control organisms (K. pneumoniae ATCC® BAA-1705—MHT positive and K. pneumoniae ATCC® BAA-1706—MHT negative) in a straight line out from the edge of the ertapenem disc. The inoculated plates were then incubated at 37°C for 24 h. Positivity for carbapenem was inferred when there was the appearance of a cloverleaf-type indentation or flattening at the intersection of the test organism and E. coli ATCC 25922 within the zone of inhibition of the carbapenem susceptibility disc as described by Anderson and recommended by CLSI.[6]

Multiplex polymerase chain reaction for detecting Klebsiella pneumoniae carbapenemase, NDM, and VIM genes

All Enterobacteriaceae that tested positive by MHT were subjected to molecular analysis. K. pneumoniae ATCC BAA-1705 and K. pneumoniae ATCC BAA-1706 were used as positive and negative controls, respectively.

DNA extraction kit (Bioneer, Daejeon, South Korea) that uses the solid-phase enzymatic principle was used to extract DNA from bacterial cells using a solid-phase enzymatic method. A loopful of the organism was harvested from fresh colony of the bacterial species grown on MacConkey agar. DNA extraction was done according to manufacturer's instructions. Twenty microliters of proteinase K was added to a clean 1.5-ml tube, and a loopful of bacterial colonies was added to the tube containing proteinase K, followed by 200 μl of binding buffer, mixed immediately by vortex mixer, then incubated at 60°C for one hour. . Two hundred microliters of GB buffer was added and mixed well by vortex mixer. Four hundred microliters of absolute methanol was added and mixed well by pipetting. The lysate was then carefully transferred into the upper reservoir of the binding column tube. The tube was then closed and centrifuged at 8000 rpm for 1 min. The tube was then opened and the binding column was then transferred to a new 2-ml tube for filtration. Five hundred microliters of washing buffer 1 (W1) was added. The tube was then closed and centrifuged at 8000 rpm for 1 min. The tube was then opened and the solution from the 2-ml tube was poured into the disposal bottle. Five hundred microliters of washing buffer 2 (W2) was carefully added to the tube and centrifuged at 8000 rpm for 1 min. The solution from the collection tube was discarded, and the collection tube was reused. It was centrifuged once more at 13,000 rpm for 1 min to completely remove ethanol. The binding column tube was transferred to a new 1.5-ml tube for elution, and 200 μl of elution buffer was added onto a binding column tube and waited for 1 min. The solution was then centrifuged at 8000 rpm for 1 min to elute. The eluted DNA is stable and was used directly for further PCR.[6]

Primer sequence

Primers were obtained from Bioneer Corporation, Daejeon, South Korea. The resistance genes blaKPC, blaNDM, and blaVIM were amplified by PCR using previously published prime [Table 1].[6]
Table 1: Adopted reverse and forward primers for target genes[6]

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DNA amplification

The prepared PCR reagents with master mixture were placed in the Eppendorf thermal cycler. Amplification was carried out according to the following thermal and cycling condition: for KPC, NDM-1, and VIM genes, initial denaturation at 94°C for 10 min, denaturation at 94°C for 30 s and then 36 cycles of annealing at 52°C for 40 s, extension at 72°C for 30 s, and final extension at 72°C for 5 min.

Data analysis

Data collected were checked, cleaned, and entered into a Microsoft Excel spreadsheet. Data analysis was done using the Statistical Product for the Service Solutions version 20.0 (SPSS, Michigan, USA). The Median and range of the respondent's age were calculated. Age was further categorized into pediatric (0–17 years) and adult (≥18 years) groups, and the frequency and percentage for each was calculated. Furthermore, the frequencies and percentages for other variables such as gender, tribe, occupation, and type of education were calculated. The susceptibility pattern of identified bacteria by various types of antibiotics was summarized using frequencies and percentages. Chi-square test or Fisher's exact test (where appropriate) was used to test the association between categorical variables. Statistical significance was set at P < 0.05.

  Results Top

A total of 76 out of the 190 samples yielded clinical isolates of Enterobacteriaceae and up to 172 (90.5%) of the respondents were adults, the median age was 52 years, with a range of 2–89 years, and slightly more than one-half 102 (53.7%) were males. A total of 120 (63.4%) had formal education, while 88 (46.3%) were gainfully employed [Table 2]. Forty-four (57.9%) clinical isolates of Enterobacteriaceae were obtained from urine, 15 (19.7%) from blood and urine specimens, 8 (10.5%) from swabs, 3 (3.9%) from both swabs and blood, 3 (3.9%) from both sputum and blood, and 3 (3.9%) from blood only.
Table 2: Sociodemographic characteristics of the respondents (n=190)

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Enterobacteriaceae accounted for 76 of the 117 culture-positive samples (n = 190). Distributions of the Enterobacteriaceae were as follows: 34 (44.7%) E. coli, 19 (25%) K. pneumoniae, 2 (2.6%) Klebsiella ozaenae, 2 (2.6%) Klebsiella oxytoca, 3 (3.9%) Proteus mirabilis, 3 (3.9%) Proteus vulgaris, 4 (5.3%) Enterobacter aerogenes, 2 (2.6%) Enterobacter agglomerans, 2 (2.6%) Enterobacter cloacae, 2 (2.6%) Citrobacter freundii, 2 (2.6%)  Salmonella More Details subsp. 3b, and 1 (1.3%) Serratia odorifera. Screening for carbapenem resistance using ertapenem disc (10 μg) showed 8 (10.5%) as resistant; confirmatory testing using the MHT revealed 6 (7.9%) as confirmed CRE. The Enterobacteriaceae demonstrated in vitro resistance to ampicillin with 100% resistance in E. coli and 84% in K. pneumoniae. Resistance to ceftriaxone was also high with 88.5% in E. coli and 63.2% in K. pneumoniae. All Proteus species were 100% resistant to both ampicillin and ceftriaxone. Similarly, the resistance of the Enterobacteriaceae to ciprofloxacin was demonstrable with 30 (88.4%) E. coli and 14 (73.7%) K. pneumonia. However, Klebsiella oxytoca was 100% sensitive to ampicillin. Gentamicin demonstrated least resistance among the Enterobacteriaceae with 14 (41.2%) E. coli to 4 (21.1%) K. pneumoniae. All the strains of E. agglomerans were susceptible to gentamicin. Susceptibility (resistance pattern) of the Enterobacteriaceae isolates to the selected antimicrobial agents is shown in [Table 3].
Table 3: Susceptibility pattern of Enterobacteriaceae isolates resistant to the tested antimicrobial agents

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[Table 4] shows the carbapenem susceptibility status of Enterobacteriaceae following the preliminary screening with ertapenem. Of the 76 species of Enterobacteriaceae screened for carbapenem resistance using ertapenem disc, 8 (10.5%) were found to be resistant. The confirmatory MHT result of the 8 isolates showed that 6 (75%) isolates tested positive for CRE. All the 8 isolates were further characterized for their molecular genotype by the use of multiplex PCR. Using DNA primers for KPC, NDM-1, and VIM genes, of the 8 isolates characterized by multiplex PCR, 4 amplified for VIM, 2 for NDM, and 1 for both VIM and KPC genes. KPC gene was detected at 785 bp, NDM-1 at 550 bp, and VIM at 382 bp genes [Figure 1]. The four VIM genes were detected in K. pneumoniae (1), E. coli (1), E. cloacae (1), and K. ozaenae (1). The two NDM genes were detected in E. coli and S. odorifera. The combined KPC and VIM gene was detected in K. pneumoniae. The risk of developing infection with CRE was associated with recent surgical procedure (P = 0.009) and history of hospital admission (P = 0.001) [Table 5].
Table 4: Modified Hodge test on screened carbapenem-resistant Enterobacteriaceae

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Figure 1: Photomicrograph of polymerase chain reaction products of carbapenemase genes: Klebsiella pneumoniae carbapenemase, NDM, and VIM genes gene was detected at 785 bp, NDM-1 at 550 bp, and VIM at 382 bp genes

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Table 5: Factors associated with carbapenem-resistant Enterobacteriaceae infections (n=76)

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  Discussion Top

Screening for CRE using ertapenem disc (10 μg) showed 8 samples (10.5%) as resistant, while confirmatory testing using the MHT revealed 6 isolates (7.9%) as confirmed CRE. Results from this study revealed that E. coli and Klebsiella spp. are still the predominant isolates as previously reported from the ICU of Fatmawati Hospital Jakarta, Indonesia.[24] There was high resistance of the Enterobacteriaceae to ampicillin, 84.2% for K. pneumoniae, 100% for E. coli, and 100% for Enterobacter spp. This finding is similar to that of a study done on bacterial spectrum and susceptibility pattern of pathogens in ICU of a secondary care hospital in the Kingdom of Saudi Arabia, with 92% resistance for E. coli and 100% for Enterobacter spp.[25] The resistance pattern to cephalosporins was also similar to that of a study done at Fatmawati Hospital, Indonesia, that showed 73.0% and 75.7% resistance to ceftazidime and ceftriaxone, respectively, among K. pneumoniae isolates as well as high resistance (85.7%) among K. ozaenae isolates to ceftriaxone.[24]

The high resistance of E. coli to ampicillin and ceftriaxone reported in this study is similar to findings from Maiduguri, Port Harcourt, and Kibret (Ethiopia).[6],[26],[27] This may have a deleterious clinical and economic implication as ampicillin and ceftriaxone may not be effective as an initial therapy for Enterobacteriaceae isolates in our patients which might necessitate the use of stronger antibiotics that are more expensive. The resistance to gentamicin is least aside carbapenem with 41.2% in E. coli, 21.1% in K. pneumoniae, and 50% in E. aerogenes. This is consistent with anecdotal evidence of non-abuse of gentamicin locally.

The finding of carbapenem resistance of 10.5% (on screening the 76 spp.) of Enterobacteriaceae using ertapenem was close to the 12.5% reported in Maiduguri.[6] The epidemiologic significance of the finding for carbapenem resistance following preliminary screening as observed from this study confirms the existence of carbapenems resistance from our locality. Hence, this calls for enhanced surveillance for this resistance threat in our health-care setting. The confirmatory test (MHT) detected 6 out of 8 isolates as carbapenemase producers giving a prevalence of 7.9% from this study. This is slightly lower than a prevalence of 10.2% recorded in Maiduguri among species of Enterobacteriaceae.[6] The relatively lower prevalence detected in this study may be attributed to the fact that only ICU patients were used compared to the study conducted in Maiduguri, Nigeria, in which all patients were used in addition to the fact that the sample size used was much less because of the limited number of bed spaces in ICU compared to medical wards. Although carbapenems are prescribed on account of the high prevalence of extended-spectrum beta-lactamase, many patients in sub-Saharan Africa cannot afford to buy them because of high costs, and therefore, many patients do not receive these agents as required. Several studies have reported that prior carbapenem therapy is not imperative for the development of carbapenem resistance for Enterobacteriaceae.[28]

With respect to the molecular basis of resistance of the Enterobacteriaceae to carbapenem, VIM gene was the predominant carbapenemase gene detected in this study. This is in agreement with the finding of a study conducted in Uganda, which reported VIM as the most prevalent gene.[29] The finding of NDM-1 in this study is worrisome as the gene has the ability to spread rapidly, unlike any other resistant mechanism in clinical microbiology.[30] KPC and VIM gene coexisted in one isolate, perhaps explaining the reason why the isolate was multidrug resistant. In this study, 1 (12.5%) of the isolates had no gene detected at all. This signifies the fact that genes other than KPC, NDM-1, and VIM may be responsible for resistance to the carbapenem group of antibiotics in this isolate.

The risk of developing infection with CRE was associated with recent surgical procedure and history of recent hospital admission. This was similar to a study finding in South Africa and Brazil, where prolonged hospital stay, prior hospital admission, use of third-generation cephalosporins 3 weeks before admission, and history of surgical procedure were significantly associated with CRE infection. [31],[32] These studies emphasize the importance of reduced hospital stay and increased surveillance on patients undergoing surgery in curtailing the spread of carbapenem-resistant organisms in health-care settings. There have been reports of associations between acquisition of CRE and other factors such as prior use of antibiotics, catheterization, and male gender. This study, however, did not find such associations. This may be due to the fewer number of patients admitted to ICU compared to the studies done in medical wards, surgical wards, or both. [6],[33]

This study established the existence of carbapenem resistance by molecular genotyping using multiplex PCR. However, the survey was limited by examination of only ICU patients. Further research is needed to explore this phenomenon in all categories of patients in Kano, Nigeria.

  Conclusion Top

The study provided evidence of the presence of CRE infections among patients admitted to ICUs in the study centers. This underscores the need for effective infection prevention and control measures to avoid the spread of CRE in hospital setting.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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