Libyan Journal of Medical Sciences

ORIGINAL ARTICLE
Year
: 2021  |  Volume : 5  |  Issue : 4  |  Page : 148--152

Prevalence of meropenem and imipenem resistance in gram-negative uropathogens in ibn sina clinic in Benghazi-Libya


Huda Mohammed Gargoum1, M Muftah Muftah2, M Alsieah Zinab3, Elsharee Khadija4,  
1 Departments of Pharmacology, Benghazi University, Benghazi, Libya
2 ICU HIV Centre, Benghazi, Libya
3 Department of Microbiology, Ibn-sena Clinic, Benghazi, Libya
4 Medicine, Benghazi University, Benghazi, Libya

Correspondence Address:
Dr. Huda Mohammed Gargoum
Department of Pharmacology, Benghazi University, Benghazi
Libya

Abstract

Background/Aims: The carbapenem resistance is increasing worldwide. Although there are a number of studies on carbapenem resistance available in western Libya, there is no adequate information in eastern Libya. The aim of the present work was to study the prevalence of both imipenem and meropenem in uropathogens in one hospital in Benghazi, a city in Libya, to know the magnitude of resistance caused by these groups of bacteria. Subjects and Methods: A total of 1011 samples of patients with urinary tract infection were collected from August 1, 2019, to April 30, 2020. Identification of the isolates was done and the antibiotic susceptibility of different uropathogens was tested for their imipenem and meropenem susceptibility. Results: The prevalence of Escherichia coli was 68.8%, followed by Klebsiella pneumonia and Proteus mirabilis (12.4% and 4.8%, respectively). The prevalence of Pseudomonas aeruginosa was also (12.4%), and the Acinetobacter baumannii comes next by 1.6%. Conclusions: Compared to different results done in different parts of Libya, the prevalence of carbapenem was increased and this expanded to other Enterobacteriaceae as P. mirabilis that has not declared in previous data in different regions in Libya.



How to cite this article:
Gargoum HM, Muftah M M, Zinab M A, Khadija E. Prevalence of meropenem and imipenem resistance in gram-negative uropathogens in ibn sina clinic in Benghazi-Libya.Libyan J Med Sci 2021;5:148-152


How to cite this URL:
Gargoum HM, Muftah M M, Zinab M A, Khadija E. Prevalence of meropenem and imipenem resistance in gram-negative uropathogens in ibn sina clinic in Benghazi-Libya. Libyan J Med Sci [serial online] 2021 [cited 2022 Dec 1 ];5:148-152
Available from: https://www.ljmsonline.com/text.asp?2021/5/4/148/338632


Full Text



 Introduction



Antimicrobial resistance (AMR) is an ongoing public health problem of the universe. It affects the management of broad spectrum of bacterial infections by limiting antibiotic prescription options and leads to the development of serious and hard to treat complications.[1] Over the past decade, different studies have witnessed the problem of AMR in Libya with various bacteria.[2],[3] One of the significant causes of rapid transmission of AMR is that the genes with resistance are carried on the genetic material or plasmid. These are replicated and transferred horizontally between various pathogens.[4] The concern of multidrug-resistant and extended-spectrum beta-lactamase (ESBL) was prevalent.[5],[6] ESBL extended to cause a resistance to the newer beta-lactam as well as nonbeta-lactam antibiotics.[7]

Carbapenems are new and potent beta-lactam antibiotics, they are usually preserved for the treatment of serious infections caused by a wide spectrum of Gram-negative bacteria.[8] At beginning of the current century, the resistance of different strains to carbapenems did not exist.[9] Spreading of infections with carbapenem-resistant Enterobacteriaceae (CRE) and other negative uropathogens such as carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa isolates (CRPA) are considered a challenge in health-care situations and it is an increasing concern globally.[9],[10],[11] In addition to efflux pumps and porin-mediated resistance, another major reason for the development of carbapenem resistance is mediated by carrying of carbapenemase genes and production of carbapenemase enzymes.[4] There are different classes of carbapenemase: Klebsiella pneumoniae carbapenemase, metalloenzymes, and enzymes (OXA-48 type) 10. The presence of carbapenemase genes such as the blaVIM-2, bla NDM, and OXA-genes is one of the most common mechanisms for these bacteria to get a resistant to the carbapenem antibiotics in several countries.[12],[13],[14],[15]

Different studies in the western part of Libya showed that the blaOXA-48 was the most prevalent gene, followed by bla NDM in CRE.[16],[17] While in CRAB, the blaOXA-23, bla-OXA24, blaOXA-48, and bla NDM-1 genes were identified, and in CRPA, the blaVIM-2 gene was the most predominant.[14],[18] The investigations on carbapenem-resistant pathogens in Benghazi city remain inadequate and limited. The aim of the present work was to study the prevalence of both imipenem and meropenem in uropathogens in one hospital in Benghazi, a city in Libya, to know the magnitude of resistance caused by these groups of bacteria.

 Subjects and Methods



Study design

A descriptive study conducted at Ibn Sina Clinic in Benghazi-Libya was done after approval from the ethical committees. A total of 1011 samples of patients with urinary tract infection were collected from August 1, 2019, to April 30, 2020. The midstream urine samples were collected in a sterile containers at early morning and sent to the laboratory within 30 minutes.

Bacterial isolates and antibiotic susceptibility testing

Urine samples were placed on cysteine lactose electrolyte deficient (CLED) agar incubated at 37°C for 24 h. A growth of >105 colony-forming units per mL of one type of organism was considered significant bacteriuria. Identification of the isolates was done by observing colonial morphology on the CLED medium.[19] The antibiotic susceptibility of different uropathogens was tested for their imipenem and meropenem susceptibility by the Clinical and Laboratory Standards Institute's disk diffusion method.[20]

 Results



In the present study, a total of 186 resistant strains of different Gram-negative isolates include Enterobacteriaceae (Escherichia coli, K. pneumonia and Proteus mirabilis), P. aeruginosa, and A. baumannii were isolated. The prevalence of Enterobacteriaceae bacteria was the most predominant (86%). E. coli, K. pneumonia, and P. mirabilis accounted for 68.8%, 12.4%, and 4.8%, respectively. It was followed by P. aeruginosa (12.4%), followed by A. baumannii 1.6% [Figure 1].{Figure 1}

A total of 19 (10.2%) different isolates were resistant to carbapenem [Figure 2]. Imipenem resistance constituted 5.4% while the prevalence of meropenem resistance was 4.8% [Figure 2]. The prevalence of carbapenem resistance in males (57.9%) was higher than in females (42.1%) [Figure 3]a. While the percentages of male resistance of imipenem and meropenem were 26.3% and 31.6%, respectively, the percentages of female resistance of both medicines were 26.3% and 15.8% [Figure 3]b, respectively. As shown in the same figure, meropenem resistance is more predominant in males than in females.{Figure 2}{Figure 3}

Eight isolates of 160 Enterobacteriaceae-resistant bacteria were resistant to imipenem (5%) [Figure 4]. The prevalence of imipenem resistance in K. pneumonia was 8.7% (2 of 23), while in E. coli was 3.9% (5 of 128) and in P. mirabilis was 11.1% (1 of 9). Eight isolates of 160 (5%) Enterobacteriaceae-resistant bacteria were resistant to meropenem [Figure 4]. The prevalence of meropenem resistance in K. pneumonia was 17.4% (4 of 23) and in E. coli was 3.1% (4 of 128). P. mirabilis bacteria were susceptible to meropenem [Figure 4]. Only 8.7% of P. aeruginosa pathogens showed resistance to imipenem, while 33% of A. baumannii were resistant to meropenem.{Figure 4}

 Discussion



Carbapenem-resistant GNB (such as A. baumannii, P. aeruginosa, and members of the family Enterobacteriaceae) has spread in the past decade and led to a serious health problem that continues to grow worldwide.[21] In the current study, the prevalence of carbapenem-resistant bacteria was 10.2%. This was nearly similar to a recent study performed in Libya in which 11 of 83 (13.3%) of Gram-negative bacteria were carbapenem-resistant strains.[22] WHO has warned of disassembly of carbapenem resistance. At the beginning of the new millennium, a few studies reported on carbapenem resistance in Libya. A review study from 1970 to 2011 reported that all detected strains were susceptible to imipenem.[3] However, in subsequent year, the prevalence of carbapenem resistance is progressively increased. A study was done in 2016 showed that the prevalence of resistance of imipenem and meropenem was 0.6% and 2.5%, respectively,[23] a higher prevalence was recorded in the present study. It has been found that the imipenem resistance accounted for 5.4% and meropenem resistance was 4.8%.

It has been noticed that in this study, there was a gender difference in carbapenem-resistance strains. Although the GNB infection is more predominant in female patients because of their anatomical structure,[24],[25] it has been found that males have a higher rate of infections with antibiotic-resistance bacteria.[26],[27],[28] This study is also consistent with previous records in which 57.9% of carbapenem resistance was found in male gender. The AMR in male patients has been explained by several factors in different studies such as age, variation in prescribing the medicine, poorer compliance, and hand hygiene, which may cause a higher rate of hospitalization.[29],[30],[31],[32]

According to different studies done in 2013 and 2015 in western regions of Libya, the prevalence of CRE isolates ranged from 6.8% to 29.2%, with blaOXA-48 being the most prevalent gene, followed by bla NDM.[16],[17] While in the present study, the total prevalence of CRE isolates was within the range of other previous studies in the western part (about 10%). The prevalence of carbapenem-resistant K. pneumonia CRK was 26% and the prevalence of carbapenem-resistant E. coli was 7%. While there were no data in Libya about carbapenem resistant in P. mirabilis, we found in this study that 11% of the pathogens were resistant to imipenem but not to meropenem. This was consistence with some recent studies that were done in different countries. In Sudan, the prevalence of carbapenem resistant in P. mirabilis was 3%, while in Turkey, it was about 17% and it was higher in eastern Asia.[33],[34],[35]

In the current study, 33% of A. baumannii isolates were only resistant to meropenem and P. aeruginosa pathogens only showed a resistance to imipenem 8.7%. Comparatively to other studies that showed 88% and 85.5% of A. baumannii isolates and P. aeruginosa were resistant to imipenem, our results were much lower. This variation between eastern and western parts of the country may be own to different genes and points of mutations in the isolated pathogens recovered from the two regions. The blaOXA-23 was detected in 86% of A. baumannii isolates recovered from Benghazi and Tripoli hospitals and the blaOXA-48 gene was detected in one pathogen isolated from Benghazi hospital. Although the blaVIM-2 gene was detected in 90% of P. aeruginosa at different regions, the presence of OprD mutations was variable in Benghazi and Tripoli hospitals.[14] Groups (G) of mutations 1, 11, and 12 were present on the detected gene of pathogens isolated from Benghazi, while G2–G10 and G13 were found in genes in pathogens isolated from Tripoli hospitals.[14]

 Conclusions



In this study, we found that the prevalence of carbapenem resistance is increased as compared to previous studies tha were done in Libya. We also found that the prevalence of K. pneumonia carbapenem resistant was predominant among CRE isolates and this consistence with several studies. Comparing to western parts of the country, this study also showed that there was a variation in the prevalence of resistance of CRAB and CRPA, and we reported for the first time the development of resistance in P. mirabilis in one of the Benghazi hospitals.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Levy SB, Marshall B. Antibacterial resistance worldwide: Causes, challenges and responses. Nat Med 2004;10:S122-9.
2Abujnah A, Zorgani A, Sabri M, El-Mohammady H, Khalek R, Ghenghesh K. Multidrug resistance and extended-spectrum beta-lactamases genes among Escherichia coli from patients with urinary tract infections in Northwestern Libya. Libyan J Med 2015;10:26412.
3Ghenghesh KS, Rahouma A, Tawil K, Zorgani A, Franka E. Antimicrobial resistance in Libya: 1970-2011. Libyan J Med 2013;8:1-8.
4Meletis G. Carbapenem resistance: Overview of the problem and future perspectives. Ther Adv Infect Dis 2016;3:15-21.
5Walsh C. Molecular mechanisms that confer antibacterial drug resistance. Nature 2000;406:775-81.
6Beyene D, Bitew A, Fantew S, Mihret A, Evans M. Multidrug-resistant profile and prevalence of extended spectrum β-lactamase and carbapenemase production in fermentative Gram-negative bacilli recovered from patients and specimens referred to National Reference Laboratory, Addis Ababa, Ethiopia. PLoS One 2019;14:e0222911.
7Paterson DL, Mulazimoglu L, Casellas JM, Ko WC, Goossens H, Von Gottberg A, et al. Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum beta-lactamase production in Klebsiella pneumoniae isolates causing bacteremia. Clin Infect Dis 2000;30:473-8.
8Rahal JJ. The role of carbapenems in initial therapy for serious Gram-negative infections. Crit Care 2008;12 Suppl 4:S5.
9Zavascki AP, Carvalhaes CG, Picão RC, Gales AC. Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: Resistance mechanisms and implications for therapy. Expert Rev Anti Infect Ther 2010;8:71-93.
10Nordmann P, Naas T, Poirel L. Global spread of Carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 2011;17:1791-8.
11Schwaber MJ, Carmeli Y. Carbapenem-resistant Enterobacteriaceae: A potential threat. JAMA 2008;300:2911-3.
12Girlich D, Bouihat N, Poirel L, Benouda A, Nordmann P. High rate of faecal carriage of extended-spectrum β-lactamase and OXA-48 carbapenemase-producing Enterobacteriaceae at a university hospital in Morocco. Clin Microbiol Infect 2014;20:350-4.
13Kraiem AG, Zorgani A, Elahmer O, Hammami A, Chaaben BM, Ghenghesh KS. New Delhi metallo-β-lactamase and OXA-48 carbapenemases in Gram-negative Bacilli isolates in Libya. Libyan J Med 2015;10:29206.
14Mathlouthi N, Areig Z, Al Bayssari C, Bakour S, Ali El Salabi A, Ben Gwierif S, et al. Emergence of carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii clinical isolates collected from some Libyan hospitals. Microb Drug Resist 2015;21:335-41.
15Sonnevend Á, Ghazawi AA, Hashmey R, Jamal W, Rotimi VO, Shibl AM, et al. Characterization of carbapenem-resistant Enterobacteriaceae with high rate of autochthonous transmission in the Arabian Peninsula. PLoS One 2015;10:e0131372.
16Ahmed M, Aghila E, Elamri S, Baptiste K. Molecular investigation of carbapenemase-producing Enterobacteriaceae isolated from a Tripoli hospital Libya. Libyan J Med Sci 2017;1:24-17.
17Zorgani A, Elahmer O, Bashein A, Hawas A, Aljerbi A, Ziglam H, et al. Extend- ed-spectrum β-lactamase- and carbapenemase-producing Enterobacteriaceae among Libyan children. EC Microbiol 2017;3:126-35.
18Zorgani A, Ziglam H. Injured Libyan combatant patients: Both vectors and victims of multiresistance bacteria? Libyan J Med 2013;8:1-2.
19Fallon D, Andrews N, Frodsham D, Gee B, Howe S, Iliffe A, et al. A comparison of the performance of Cystine Lactose Electrolyte Deficient (CLED) agar with Oxoid Chromogenic Urinary Tract Infection (CUTI) medium for the isolation and presumptive identification of organisms from urine. J Clin Pathol 2002;55:524-9.
20Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing. Wayne, Pennsylvania: Clinical and Laboratory Standards Institute (CLSI); 2007.
21WHO. Antimicrobial Resistance: Global Report on Surveillance. WHO press. Switzerland ;2014. Availablefrom: https://www.who.int/publications/i/ item/9789241564748. [Last accessed on2021 Jun 10].
22Slimene K, El Salabi AA, Dziri O, Mabrouk A, Miniaoui D, Gharsa H, et al. High carbapenem resistance caused by VIM and NDM enzymes and OprD alteration in nonfermenter bacteria isolated from a Libyan hospital. Microb Drug Resist 2021;27:1546-54.
23Mohammed MA, Alnour TM, Shakurfo OM, Aburass MM. Prevalence and antimicrobial resistance pattern of bacterial strains isolated from patients with urinary tract infection in Messalata central hospital, Libya. Asian Pac J Trop Med 2016;9:771-6.
24Ebie M, Kandakai-Olukemi Y, Ayanbadejo J, Tanyigna KB. Urinary tract infections in a Nigerian military hospital. Nig J Microbiol 2001;15:31-7.
25Garofalo CK, Hooton TM, Martin SM, Stamm WE, Palermo JJ, Gordon JI, et al. Escherichia coli from urine of female patients with urinary tract infections is competent for intracellular bacterial community formation. Infect Immun 2007;75:52-60.
26Control ECfDPa. Country Summaries-Antimicrobial Resistance in the EU/EEA (EARS-Net); 2021. Available from: https://www.ecdc.europa.eu/en/publications-data/surveillance-antimicrobial-resistance-europe-2019. [Last accessed on 2021 Jun 10].
27Koppe U, von Laer A, Kroll LE, Noll I, Feig M, Schneider M, et al. Carbapenem non-susceptibility of Klebsiella pneumoniae isolates in hospitals from 2011 to 2016, data from the German Antimicrobial Resistance Surveillance (ARS). Antimicrob Resist Infect Control 2018;7:71.
28Walter J, Haller S, Blank HP, Eckmanns T, Abu Sin M, Hermes J. Incidence of invasive meticillin resistant Staphylococcus aureus infections in Germany, 2010 to 2014. Euro Surveill 2015;20:30067 [doi: 10.2807/1560 7917.ES.2015.20.46.30067].
29Humphreys H, Fitzpatick F, Harvey BJ. Gender differences in rates of carriage and bloodstream infection caused by methicillin-resistant Staphylococcus aureus: Are they real, do they matter and why? Clin Infect Dis 2015;61:1708-14.
30Neubeiser A, Bonsignore M, Tafelski S, Alefelder C, Schwegmann K, Rüden H, et al. Mortality attributable to hospital acquired infections with multidrug-resistant bacteria in a large group of German hospitals. J Infect Public Health 2020;13:204-10.
31Schröder W, Sommer H, Gladstone BP, Foschi F, Hellman J, Evengard B, et al. Gender differences in antibiotic prescribing in the community: A systematic review and meta-analysis. J Antimicrob Chemother 2016;71:1800-6.
32Vincent JL, Sakr Y, Singer M, Martin-Loeches I, Machado FR, Marshall JC, et al. Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA 2020;323:1478-87.
33Baran I, Aksu N. Phenotypic and genotypic characteristics of carbapenem-resistant Enterobacteriaceae in a tertiary-level reference hospital in Turkey. Ann Clin Microbiol Antimicrob 2016;15:20.
34Islam M, Mohammed MN. Detection of carbapenem-resistant Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis clinical isolates in Khartoum. Sudan Lab Med J 2019;3:16-20.
35Bontron S, Poirel L, Kieffer N, Savov E, Trifonova A, Todorova I, et al. Increased resistance to carbapenems in Proteus mirabilis mediated by amplification of the blaVIM-1-carrying and IS26-associated class 1 integron. Microb Drug Resist 2019;25:663-7.