Search

Aims: Enterococci are implicated in hospital-acquired infections and show high tenacity on inanimate objects in the hospital environment. This study investigated the prevalence of Enterococcus spp. in selected wards in public hospitals at four levels of healthcare from a district in KwaZulu-Natal, South Africa., Methods and Results: Swabs were collected from frequently touched areas in the paediatric wards and intensive care units (ICUs). Presumptive Enterococcus spp. were isolated and confirmed to genus and species levels, followed by Kirby-Bauer disk diffusion against 14 antibiotics. The results showed that enterococci were recovered from all 11 surfaces tested with the highest contamination rate observed on occupied beds and mops used to clean floors. A total number of 295 Enterococcus was identified. Polymerase chain reaction identified Enterococcus faecalis 83.1% (245/295) and Enterococcus faecium 12.9% (38/295), while whole genome sequencing identified Enterococcus gallinarum 2.0% (6/295) and Enterococcus casseliflavus 2.0% (6/295). Significant prevalence was observed in paediatric wards 64.1% (189/295) compared with the ICUs 35.9% (106/295), p < 0.05, in central, regional and district hospitals. Collectively, 82.0% (242/295) of enterococcal isolates were multidrug resistant, and 80 different antibiograms were observed. The most prominent antibiogram for E. faecium was CIP-RIF-NIT-TET-ERY and for E. faecalis CIP-TET-ERY., Conclusion: E. faecalis was the most frequent enterococcal species isolated in all the hospitals investigated and correlates with studies conducted elsewhere. A substantially greater number of isolates were recovered from the paediatric wards compared with ICUs, and thus improved standards should be developed for infection control practices. It is suggested that the elevated use of antibiotics contributed to the increased nonsusceptible isolates observed from ICUs. This study highlighted the high recovery rate of enterococci in the hospital environment even in a nonoutbreak setting., Significance and Impact of the Study: Enterocci had a high prevalence rate on the surfaces within the hospitals studied. This study gives an insight into the possible roles all healthcare staff may play in infection control intervention, including proper handling of hospital cleaning equipment and lack of knowledge about the potential for bacteria dissemination., (© 2021 The Society for Applied Microbiology.)

Aims: We hypothesized and confirmed that tannic acid (TA) reverses carbapenem resistance by inhibiting carbapenemases in class A and B carbapenemase-producing Enterobacteriaceae., Methods and Results: Minimum inhibitory concentrations of carbapenems in the presence and absence of TA and other efflux pump inhibitors, TA-carbapenemases inhibition assays and computational studies showed that TA had the greatest effect on metallo-β-lactamases (MBLs) followed by class A serine-β-lactamases (SBLs). TA completely reversed the MICs of MBL producers from between 32 and ≥512 mg l -1 to susceptible values (<4 mg l -1 ) while substantially reducing the MICs of SBLs from between 16 and >512 mg l -1 to <4 to 16 mg l -1 . Tolerable cytotoxic effect was observed for the concentrations tested (8-1024 mg l -1 ). TA inhibited enzymes with a marked difference of ≈50% inhibition (IC 50 ) for NDM-1 (270 μmol l -1 ) and KPC-2 (15  μmol l -1 )., Conclusion: TA inhibited both MBLs and SBLs by targeting their hydrophobic sites. Moreover, TA had a stronger binding affinity for MBLs than SBLs as the MBLs, specifically VIM-1 (-43·7220 ± 0·4513 kcal mol -1 ) and NDM-1(-44·2329 ± 0·3806 kcal mol -1 ), interact with a larger number of their catalytic active-site residues than that of OXA-48 (-22·5275 ±  0·1300 kcal mol -1 ) and KPC-2 (-22·1164 ± 0·0111 kcal mol -1 )., Significance and Impact of the Study: Tannic acid or its analogues could be developed into carbapenemase-inhibiting adjuvants to restore carbapenem activity in CRE infections, save many lives and reduce healthcare associated costs., (© 2018 The Society for Applied Microbiology.)

Objectives: The anti-leprosy drug clofazimine has been shown to have antimicrobial activity against Mycobacterium tuberculosis and has been associated with treatment-shortening activity in both clinical and preclinical studies of TB chemotherapy. However, a reported lack of early bactericidal activity (EBA) in TB patients has raised questions regarding the usefulness of clofazimine as an anti-TB drug. Our objective was to systematically evaluate the EBA of clofazimine in vitro and in vivo to provide insight into how and when this drug exerts its antimicrobial activity against M. tuberculosis., Methods: We evaluated the 14 day EBA of clofazimine (i) in vitro at concentrations ranging from 4 times below to 4 times above the MIC for M. tuberculosis and (ii) in vivo in infected BALB/c mice at doses ranging from 1.5 to 100 mg/kg/day, and serum clofazimine levels were measured. In both experiments, isoniazid was used as the positive control., Results: In vitro, clofazimine, at any concentration tested, did not exhibit bactericidal activity during the first week of exposure; however, in the second week, it exhibited concentration-dependent antimicrobial activity. In vivo, clofazimine, at any dose administered, did not exhibit bactericidal activity during the first week, and limited antimicrobial activity was observed during the second week of administration. While serum clofazimine levels were clearly dose dependent, the antimicrobial activity was not significantly related to the dose administered., Conclusions: Our data suggest that clofazimine's delayed antimicrobial activity may be due more to its mechanism of action rather than to host-related factors., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

A literature review was undertaken to ascertain the molecular basis for tigecycline and colistin resistance mechanisms and the experimental basis for the detection and delineation of this resistance particularly in carbapenemase-producing Gram-negative bacteria. Pubmed, Google Scholar and Science Direct were searched with the keywords colistin, tigecycline, resistance mechanisms and detection methods. Trans-complementation and comparative MIC studies, mass spectrometry, chromatography, spectrofluorometry, PCR, qRT-PCR and whole genome sequencing (WGS) were commonly used to determine tigecycline and colistin resistance mechanisms, specifically modifications in the structural and regulatory efflux (acrAB, OqxAB, kpgABC adeABC-FGH-IJK, mexAB-XY-oprJM and soxS, rarA robA, ramRAB marRABC, adeLRS, mexRZ and nfxb) and lipid A (pmrHFIJFKLM, lpxA, lpxC lpxD and mgrB, pmrAB, phoPQ,) genes respectively. Mutations in the ribosomal 16S rRNA operon rrnBC, also yielded resistance to tigecycline through target site modifications. The mcr-1 gene conferring resistance to colistin was identified via WGS, trans-complementation and a murine thigh infection model studies. Common detection methods are mainly antibiotic sensitivity testing with broth microdilution while molecular identification tools are mostly PCR and WGS. Spectrofluorometry, MALDI-TOF MS, micro-array and real-time multiplex PCR hold much promise for the future as new detection tools., (© 2016 The Society for Applied Microbiology.)

Aims: This study aimed at investigating the use of metal chelators as potential metallo-β-lactamase inhibitors (MBL)., Methods and Results: The minimum inhibitory concentration (MIC) of meropenem was ascertained alone and in combination with various concentrations of macrocyclic (1,4,7- triazacyclononane-1-glutaric acid-4,7-diacetic acid = NODAGA) peptide derivatives and acyclic (N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine = TPEN and di-(2-picolyl)amine = DPA) metal chelators using the broth microdilution method. MICs of meropenem against carbapenem-resistant enterobacteriaceae (CRE) producing MBLs were decreased to concentrations as low as 0·06 mg l(-1) in the presence of some metal chelators. TPEN at 4 and 8 mg l(-1) showed the best activity by decreasing meropenem MICs to 0·5 and 0·06 mg l(-1) , respectively, for some New Delhi Metallo-beta-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase (VIM) -producing enterobacteriaceae. DPA at 8 and 16 mg l(-1) was also able to decrease meropenem MICs to 1 and 0·125 mg l(-1) , respectively, for these CREs. NODAGA peptide derivatives showed the least inhibition as 32 mg l(-1) was required for meropenem MICs to be decreased to 0·06 mg l(-1) against an NDM-1 producing isolate., Conclusion: The various metal chelators, TPEN, DPA and NODAGA peptide derivatives were able to inhibit the MBLs in decreasing order of activity, rendering CREs susceptible to meropenem., Significance and Impact of the Study: In the absence of new antibiotics, this study evaluated metal chelators as potential MBL inhibitors., (© 2016 The Society for Applied Microbiology.)

Objectives: Campylobacter jejuni isolated from broiler and layer chickens from registered abattoirs in KwaZulu-Natal, South Africa, were tested for their susceptibility to eight antibiotics., Methods: Using agar dilution, susceptibility to eight antibiotics was determined for C. jejuni recovered from the caeca., Results: A total of 155 isolates were collected of which 77 were identified as C. jejuni (broilers n = 56 and layers n = 21). Resistance was highest to tetracycline (broilers 98.2% and layers 100%) and ceftriaxone (broilers 96.4% and layers 100%). High susceptibility was found to ciprofloxacin (broilers 91% and layers 76%) and gentamicin (broilers 98% and layers 81%). Susceptibilities to each of the antibiotics for the broilers and layers, respectively, were: 50% and 57% for erythromycin, 45% and 24% for clarithromycin, 68% and 43% for ampicillin and 64% and 48% for nalidixic acid. Statistically significant differences were detected for the MIC(50) of gentamicin, ciprofloxacin and tetracycline between broilers and layers (P < 0.001) with the MIC(90) of gentamicin also of significant difference (P = 0.01). Multiresistance was detected in 23% and 43% of the isolates from broiler and layer chickens, respectively., Conclusions: Mass therapy procedures used in animal husbandry have a potential impact on antibiotic resistance development in C. jejuni.