Resistance and Co-Resistance of Metallo-Beta-Lactamase Genes in Diarrheal and Urinary-Tract Pathogens in Bangladesh

Abstract

Carbapenems are the antibiotics of choice for treating multidrug-resistant bacterial infections. Metallo-β-lactamases (MBLs) are carbapenemases capable of hydrolyzing nearly all therapeutically available beta-lactam antibiotics. Consequently, this research assessed the distribution of two MBL genes and three β-lactamases and their associated phenotypic resistance in diarrheal and urinary-tract infections (UTIs) to guide future policies. Samples were collected through a cross-sectional study, and β-lactamase genes were detected via PCR. A total of 228 diarrheal bacteria were isolated from 240 samples. The most predominant pathogens were Escherichia coli (32%) and Klebsiella spp. (7%). Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 50.4%, 65.6%, 66.8%, 80.5%, 54.4%, 41.6%, 25.7%, 41.2%, 37.2%, and 42.9%, respectively. A total of 142 UTI pathogens were identified from 150 urine samples. Klebsiella spp. (39%) and Escherichia coli (24%) were the major pathogens isolated. Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 93.7%, 75.0%, 91.5%, 93.7%, 88.0%, 72.5%, 13.6%, 44.4%, 71.1%, and 43%, respectively. Twenty-four diarrheal isolates carried blaNDM-1 or blaVIM genes. The overall MBL gene prevalence was 10.5%. Thirty-six UTI pathogens carried either blaNDM-1 or blaVIM genes (25.4%). Seven isolates carried both blaNDM-1 and blaVIM genes. MBL genes were strongly associated with phenotypic carbapenem and other β-lactam antibiotic resistance. blaOXA imparted significantly higher phenotypic resistance to β-lactam antibiotics. Active surveillance and stewardship programs are urgently needed to reduce carbapenem resistance in Bangladesh.

Keywords: Bangladesh; antimicrobial resistance; antimicrobial stewardship programs; blaNDM-1; blaVIM; co-resistance; diarrhea; metallo-beta-lactamase; urinary tract infections.

Figure 1

Phenotypic antibiotic resistance in diarrheal and UTI isolates. (A) Antibiotic susceptibilities were evaluated largely by the standard disk-diffusion methods for both diarrheal and UTI pathogens against amoxicillin-clavulanic acid (AMC 30 µg), aztreonam (ATM 30 µg), cefuroxime sodium (CXM 30 µg), cefixime (CFM 30 µg), cefepime (FEP 30 µg), imipenem (IMP 10 µg), meropenem (MEM 10 µg), gentamicin (CN 30 µg), netilmicin (NET 30 µg), and amikacin (AK 30 µg). ‘ns’ indicates no statistical differences (p > 0.05), ‘*’ means statistical differences were observed (p = 0.05 to 0.01) and ‘**’ indicates highly statistical differences were found. (B) Differential meropenem minimum inhibitory concentrations (MICs) of diarrheal and UTI isolates are shown. Percentages of bacteria at each MIC level were calculated. The X-axis indicates each of the MIC points, and the Y-axis represents the percentages of isolates at a particular MIC. p-values were calculated from the differences in MIC values between the two groups of clinical pathogens. ‘ns’ shows no statistical differences (p > 0.05), ‘*’ means significant statistical differences (p = 0.05 to 0.01), and ‘**’ indicates highly significant statistical differences.