Prevalence and Characterization of Carbapenem-Resistant Enterobacteriaceae Isolated from Mulago National Referral Hospital, Uganda
August
Prevalence and Characterization of Carbapenem-Resistant Enterobacteriaceae Isolated from Mulago National Referral Hospital, Uganda
Deogratius Okoche 0 1
Benon B. Asiimwe 0 1
Fred Ashaba Katabazi 0 1
Laban Kato 0 1
Christine F. Najjuka 0 1
0 Editor: Qijing Zhang, Iowa State University , UNITED STATES
1 Department of Medical Microbiology, Makerere University College of Health Sciences , Kampala , Uganda
Carbapenemases have increasingly been reported in enterobacteriaceae worldwide. Most carbapenemases are plasmid encoded hence resistance can easily spread. Carbapenemresistant enterobacteriaceae are reported to cause mortality in up to 50% of patients who acquire bloodstream infections. We set out to determine the burden of carbapenem resistance as well as establish genes encoding for carbapenemases in enterobacteriaceae clinical isolates obtained from Mulago National Referral Hospital, Uganda.
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This was a cross-sectional study with a total of 196 clinical isolates previously collected
from pus swabs, urine, blood, sputum, tracheal aspirates, cervical swabs, endomentrial
aspirates, rectal swabs, Vaginal swabs, ear swabs, products of conception, wound biopsy
and amniotic fluid. All isolates were subjected to phenotypic carbapenemase screening
using Boronic acid-based inhibition, Modified Hodge and EDTA double combined disk test.
In addition, all the isolates were subjected to PCR assay to confirm presence of
carbapenemase encoding genes.
The study found carbapenemase prevalence of 22.4% (44/196) in the isolates using
phenotypic tests, with the genotypic prevalence slightly higher at 28.6% (56/196). Over all, the
most prevalent gene was blaVIM (21,10.7%), followed by blaOXA-48 (19, 9.7%), blaIMP
(12, 6.1%), blaKPC (10, 5.1%) and blaNDM-1 (5, 2.6%). Among 56 isolates positive for 67
carbapenemase encoding genes, Klebsiella pneumonia was the species with the highest
number (52.2%). Most 32/67(47.7%) of these resistance genes were in bacteria isolated
from pus swabs.
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There is a high prevalence of carbapenemases and carbapenem-resistance encoding
genes among third generation cephalosporins resistant Enterobacteriaceae in Uganda,
indicating a danger of limited treatment options in this setting in the near future.
Enterobacteriaceae is a family of gram-negative bacteria and members are mainly inhabitants
of the gut flora [1,2]. Most members of this family are pathogenic and cause such human
infections as gastrointestinal infections, septicemia, pneumonia, meningitis, peritonitis and
urinary tract infections [2,3]. These organisms easily acquire and transfer drug resistance genes
through plasmids and transposons. Acquisition of these genes leads to production of
β-lactamases of which extended spectrum β-lactamases (ESBLs) are the most common [3]. ESBLs in
enterobacteriaceae are reported to coexist with resistance to other antimicrobial classes and
as such these organisms become multi-drug resistant hence limiting treatment options for
infections. Carbapenem antibiotics have been used as a last resort to treat infections caused by
multidrug resistant gram negative bacteria [4,5]. However, there has been emergence of
carbapenem resistant bacteria which now have a worldwide presence [2], thought to be due to high
antibiotic use and misuse without proper diagnosis of infection, or self-medication by patients
[6]. As a result, there is selective pressure on microorganisms, which in turn enhances
antimicrobial resistance. Infections caused by bacteria resistant to carbapenems often fail to respond
to conventional treatment, and are said to kill up to 50% of patients with bloodstream infection
due to them [2,7].
Resistance to carbapenems is mostly due to the production of carbapenemases, which are
βlactamase enzymes with a capacity to hydrolyze not only the carbapenems but also all the
other beta lactam agents [8]. The most common carbapenemases include veronica integron
metallo-beta-lactamases types (VIM), imipenemase (IMP) types, Klebsiella pneumoniae
carbapenemase (KPC), oxacillinase-48 (OXA-48), and New Delhi metallo-beta-lactamase-1 (NDM-1),
encoded by carbapenem resistance determining genes blaVIM, blaIMP, blaKPC, blaOXA-48,
and blaNDM, respectively [2]. Phenotypic assays are used to identify carbapenemase activity
while molecular assays have been developed to identify carbapenemase encoding genes [2,9].
In most sub-Saharan Africa, there is limited data on the prevalence and distribution of
carbapenem resistance among enterobacteriaceae. In East Africa, a few studies have been done in
Kenya and Tanzania. A surveillance study in Kenya reported isolation of NDM-1 producing
Klebsiella pneumoniae from urine samples [10], while in Tanzania a study reported a
prevalence of 35.24% carbapenemase genes among multi-drug resistant gram-negative bacteria
based the PCR assays [5]. Isolation of carbapenemase producers among ESBL isolates was also
reported in South Africa [11,12]. In Uganda, however, no d (...truncated)