Current challenges and emergence of carbapenemase-producing bacteria: a brief report from a libyan hospital
Asma Elramalli1, Nariman Almshawt2, Mohamed Omar Ahmed2,&
1Tripoli Medical Centre, Tripoli, Libya, 2Department of Microbiology and Parasitology, Faculty of Veterinary Medicine, University of Tripoli, Libya
Mohamed Omar Ahmed, Department of Microbiology and Parasitology, Faculty of Veterinary Medicine, University of Tripoli, Libya
A collection of 94 Gram-negative bacteria isolates, showing different antimicrobial resistance phenotypes including to the carbapenem classes was investigated. Strains were originated form clinical sources from a single hospital in Tripoli, Libya during 2015 and were identified based on culture and phenotype characteristics, and fully characterized by the VITEK automated system. Forty-eight percent (48%) of the collection was Acinetobacter baumannii, 50% was Klebsiella pneumoniae and 2% was Escherichia coli. Resistance to the carbapenem classes was reported in 96% of the A. baumannii strains and 94% of the K. pneumonia strains. Seventy-eight percent (78%) of the isolates showed different multidrug-resistant (MDR) phenotypes, with K. pneumoniae expressing the highest proportion (91%). Emergence of resistance to carbapenems among the Gram-negative strains is a challenging global problem, particularly for Africa. Surveillance of these pathogens is urgently required in the Libyan healthcare settings.
The emergence of antimicrobial resistance (AMR) is a major threat
to human health and is occurring at an alarming rate throughout the globe,
diminishing the already limited therapeutic options .
Low-income regions, such as Africa, are at high and particular risk. Such
threats are complicated by the underdeveloped regional conditions and socioeconomic
factors that are associated with health and community-acquired pathogens
. AMR in Africa is a rising problem and frequently
reported from clinical, non-clinical and environmental sources [2,3].
Carbapenems are potent 46;-lactam antibiotics that are considered as the last
resort option for treating serious nosocomial infections caused by a broad
spectrum of Gram-negative bacteria . Prior to 2000,
only few clinical isolates showed resistance to carbapenems, mostly represented
by Acinetobacter baumannii and Pseudomonas aeruginosa. Thereafter, carbapenem
resistance has emerged as a major, global health concern and a major clinical
problem . Carbapenemase-producing bacteria has come
to the forefront as a global concern representing a serious medical and
public health issue due to multidrug resistances (MDRs) that involve valuable
therapeutic choices, including the so-called drugs of last resort [6-9].
Over the past decade, studies and investigations have reported the problem of
AMR in Libya among different nosocomial bacterial, with a particular focus on
methicillin-resistant Staphylococcus aureus (MRSA) [10
Recent and increasing reports have also documented the carbapenamase-producing
bacteria, and the majority of cases have involved Libyan traveller patients [6
These recent and limited studies have reported different carbapenemase-encoding
genes in Gram-negative bacteria, including the blaVIM-2, blaNDM and OXA-genes
]. Nevertheless, surveillance
and epidemiological investigations on AMR bacterial pathogens in this particular
region remain inadequate, limited and incomplete.
In this short report, we investigate and provide data of the species spectrum
and antibiotic susceptibility patterns of 94 Gram-negative bacteria that were
collected in 2015 from clinical cases at a single Libyan hospital located in
Tripoli. These strains were isolated and collected on the basis of expressed
resistance to the carbapenem classes only. This brief work aimed to report and
discuss the current status and potential concern of carbapenemase-producing Gram-negative
bacteria in Libyan hospitals.
The 94 Gram-negative bacterial strains were initially isolated and
identified based on culture and biochemical characteristics (i.e.
Gram stain, catalase reactivity, and API 20E system). Isolates
were further defined
and characterized at species level and the antibiotic susceptibility
profile was determined using the VITEK automated system (VITEK-Compact
2). The strains
were selected and collected based on the expressed resistance to
at least one carbapenem class (i.e. meropenem or/and ertapenem)
and stored at -20°C.
The VITEK system tested A. baumannii only against meropenem, while
the E. coli and K. pneumoniae were tested against both of the carbapenem
The antibiotic susceptibility profile, including MDR phenotypes
(based on the resistance to ≤5 different antimicrobial classes) were
Among the collection of tested isolates, 45/94 (48%) were A. baumannii, 47/94 (50%) were K. pneumoniae and only 2/94 (2%) were E. coli. Among the A. baumannii strains, 43/45 (96%) showed resistance to meropenem. Among the K. pneumonia strains, 33/47 (70%) showed resistance to meropenem and 44/47 (94%) showed resistance to ertapenem (Table 1). Both E. coli isolates show resistance to ertapenem and only one strain show resistance to meropenem. A total of 73/94 (78%) of the strains showed different MDR phenotypes, with 67% of A. baumannii and 91% of K. pneumoniae strains accounting for this.
S. aureus, Pseudomonas spp. and Klebsiella spp. were previously reported as the most frequent causes of nosocomial infections, highlighting the reported emerging challenge of antimicrobial resistance in Libyan hospitals . A recent investigation involving a single Libyan hospital found P. aeruginosa, A. baumannii and S. aureus as the most identified nosocomial bacterial strains expressing high rates of MDR phenotypes, including to the cephalosporins and carbapenems (personal unpublished 2015 data). In the current brief report, A. baumannii and K. pneumonia were identified as the dominant bacteria among the collection and showed a high level of resistance to different antimicrobial classes of the carbapenems. The Klebsiella strains, in particular, showed a remarkable rate of MDRs and different antimicrobial resistance patterns (Table 1). Previously, Extended spectrum beta-lactamases (ESBLs)- in the Gram-negative isolates from Libya hospitals was reported at a range of 9-15% . Generally, MDR and ESBLs are frequent among the clinical strains of Gram-negative rods of P. aeruginosa, A. baumannii and K. pneumonia, and show the concomitant resistance phenotypes [3, 13, 19].
The documented cases of carbapenemase-producing bacteria from/within Libya have exclusively involved Libyan travellers and described MDR phenotypes in patients with high co-colonization rates and a pre-hospitalization history in Libyan healthcare settings [12-16
]. Moreover, this reported MDR in K. pneumonia and A. baumannii strains were shown to harbour either or a combination of OXA-48, OXA-23 or NDM-1. Yet another report demonstrated the presence of blaVIM-2 gene in P. aeruginosa and of OXA-carbapenemase-encoding genes (the blaOXA-23 type, followed by blaOXA-24- and blaOXA-48- genes) in A. baumannii isolates from hospitalized patients in a Libyan hospital [17
The carbapenemase-producing bacteria, are generally recognized as difficult to identify and estimate [9
]. The current estimates of carbapenemase-producing bacteria for Africa range from 2.3% to 67.7% [8
]. The North African and Mediterranean regions have recently been designated as an endemic/reservoir area of the carbapenemase-producing bacteria (i.e. OXA-48 type) [6
]. Globally KPC VIM IMP NDM and OXA-48 are the most prevalent β-lactamase classes produced by the carbapenemase-producing bacteria [9
The carbapenem-resistant bacteria in Gram negative strains, in particular, are a global emergent problem and surveillance and follow-up studies focused on these pathogens are urgently needed in Libya. Due to our limited resources at the present time, investigation of ESBL genes within the current collection was not carried out, but future investigations are needed since they will allow for estimation of the presence and extent of carbapenemase-producers in the Gram-negative bacteria in Libyan hospitals.
The antimicrobial resistance (AMR) pose a serious medical and public health concern. The recent published reports and the current information indicate a current and prospective concern of AMR pathogens. The report and rise of AMR in Libya has been mainly attributed to the consumption of antibiotic drugs (i.e. β-lactam drugs) and to the improved identification methods and applied laboratory skills. However, epidemiological data and molecular investigations remain lacking for from healthcare settings (nosocomial isolates) and are even more rare from community-acquired sources. Certainly, the lack of epidemiological and molecular investigations (particularly from the community), the lack of surveying and monitoring studies, as well as the socioeconomic factors and underdeveloped healthcare infrastructure play important roles in the development and spread of AMR. Professional upgrading of healthcare personnel, along with educational campaigns to increase public awareness of AMR and of the importance of controlled use of antibiotics are too important steps that need to be taken towards gaining control over the spread of AMR.
What is known about this topic
- Carbapenemase-producing bacteria is an emerging and global problem
especially for developing countries, particularly Africa;
- It is already reported from different regions mainly from north African
countries and included in the paper;
- Also reported from Libyan hospitals and travelled patients and including other north African countries but limited attention is given to it and limited information is currently available.
What this study adds
- Show the importance to focus on this coming up emerging problem
and its effect on antimicrobial therapeutic options and how
critical is such issue for African countries in particular;
- This short paper report the most important clinical isolates and
can aid researchers to what to focus in their next research
- The revelation of this brief report also help clinicians
to understand the serious problem of emerging carbapenemase-producing
bacteria and the limitation of therapeutic options with these
strains and the extent of the problem in this north African
country, i.e. Libya and the need to take appropriate actions.
The author declare no competing interest.
MOA, analyzed and interpreted the data, and drafted the manuscript. AKE and NFA performed the laboratory work and interpretation of the data. Manuscript was approved by all authors.
Table 1: antimicrobial resistance of the collection-strains
- World Health Organization. Antimicrobial resistance: global report on surveillance, Geneva;2014. Google Scholar
- WHO-Antimicrobial resistance in the African Region: Issues, challenges and actions proposed Key determinants for health in the African Region African Health Monitor;16, 2013. http://www.aho.afro.who.int/en/ahm/issue/16. Google Scholar
- Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: past, present and future. Antimicrob Agents Chemother. 2011; 55(11): 4943-4960. PubMed | Google Scholar
- Uwingabiye J, Frikh M, Lemnouer A, Bssaibis F, Belefquih B, Maleb A, Dahraoui S, Belyamani L, Bait A, Haimeur C, Louzi L, Ibrahmi A, Elouennass M. Acinetobacter infections prevalence and frequency of the antibiotics resistance: comparative study of intensive care units versus other hospital units. Pan Afr Med J. 2016; 23:191. PubMed | Google Scholar
- Zavascki AP, Carvalhaes CG, Picao RC, Gales AC. Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: resistance mechanisms and implications for therapy. Anti-Infect Ther. 2010; 8(1): 71-93. PubMed | Google Scholar
- Djahmi N, Dunyach-Remy C, Pantel A, Dekhil M, Sotto A, Lavigne J. Epidemiology of carbapenemase-producing Enterobacteriaceae and Acinetobacter baumannii in Mediterranean countries. Biomed Res Int. 2014;10:305784. doi: 10.1155/2014/305784. Epub 2014 May 13. PubMed | Google Scholar
- Bakour S, Olaitan AO, Ammari H, Touati A, Saoudi S, Saoudi K, Rolain JM. Emergence of Colistin- and Carbapenem-Resistant Acinetobacter baumannii ST2 Clinical Isolate in Algeria: First Case Report. Microb Drug Resist. 2015 Jun; 21(3): 279-85. PubMed | Google Scholar
- Manenzhe RI, Zar HJ, Nicol MP, Kaba M. The spread of carbapenemase-producing bacteria in Africa: a systematic review. J Antimicrob Chemother. 2015 Jan; 70(1): 23-40. PubMed | Google Scholar
- Nordmann P, Naas T, Poirel L. Global spread of Carbapenemase-producing
Enterobacteriaceae. Emerg Infect Dis. 2011; 17(10): 1791-8. PubMed | Google
- Ghenghesh KS, Rahouma A, Tawil K, Zorgani A, Franka E. Antimicrobial resistance in Libya: 1970-2011. Libyan J Med. 2013 Mar 27; 8:1-8. doi: 3402/ljm. v8i0.20567. PubMed | Google Scholar
- Abujnah AA, Zorgani A, Sabri MA, El-Mohammady H, Khalek RA, Ghenghesh KS. Multidrug resistance and extended-spectrum beta-lactamases genes among Escherichia coli from patients with urinary tract infections in Northwestern Libya. Libyan J Med. 2015 Feb 2; 10:26412. doi: 10.3402/ljm. v10.26412. eCollection 2015. PubMed | Google Scholar
- Kaase M, Pfennigwerth N, Szabados F, Gatermann S. OXA-48, OXA-23 and NDM-1 carbapenemases in Gram-negative bacteria from patients from Libya. "the Twenty-Second European Congress of Clinical Microbiology and Infectious Diseases, London" (ECCMID), London, UK, 20 2014 May 13;10:305784. doi: 10.1155/2014/305784. PubMed | Google Scholar
- Pirs M, Andlovic A, Cerar T, zohar-cretnik T, Kobola L, Kolman J, Frelih T, Presern-Strukelj M, Ruzic-Sabljic E, Seme K. A case of OXA-48 carbapenemase-producing Klebsiella pneumoniae in a patient transferred to Slovenia from Libya, November 2011. Euro Surveill. 2011 Dec 15; 16(50):20042. PubMed | Google Scholar
- Ben Nasr A, Decré D, Compain F, Genel N, Barguellil F, Arlet G. Emergence of NDM-1 in association with OXA-48 in Klebsiella pneumoniae from Tunisia. Antimicrob Agents Chemother. 2013 Aug; 57(8):4089-90. PubMed | Google Scholar
- Hammerum AM, Larsen AR, Hansen F, Justesen US, Friis-Møller A, Lemming LE, Fuursted K, Littauer P, Schønning K, Gahrn-Hansen B, Ellermann-Eriksen S, Kristensen B. Patients transferred from Libya to Denmark carried OXA-48-producing Klebsiella pneumoniae, NDM-1-producing Acinetobacter baumannii and meticillin-resistant Staphylococcus aureus. Int J Antimicrob Agents. 2012 Aug; 40(2): 191-2. PubMed | Google Scholar
- Zorgani A, Ziglam H. Injured Libyan combatant patients: both vectors and victims of multiresistance bacteria. Libyan J Med. 2013;8:20325 doi: 10.3402/ljm. v8i0.20325. Epub 2013 Feb 12. PubMed | Google Scholar
- Mathlouthi N, Areig Z, Al Bayssari C, Bakour S, Ali El Salabi A, Ben Gwierif S, Zorgani AA, Ben Slama K, Chouchani C, Rolain JM. Emergence of Carbapenem-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Clinical Isolates Collected from Some Libyan Hospitals. Microb Drug Resist. 2015 Jun; 21(3): 335-41. PubMed | Google Scholar
- Kraiem 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 Aug 19; 10:29206. doi: 10.3402/ljm. v10.29206. eCollection 2015. PubMed | Google Scholar
- Potron A, Poirel L, Nordmann P. Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: Mechanisms and epidemiology. Int J Antimicrob Agents. 2015 Jun; 45(6):568-85. PubMed | Google Scholar