Passing the baton to pharmacists and nurses: New models of antibiotic stewardship for South Africa?

No Abstrac

Genetic features of MCR-1-producing colistin-resistant Escherichia coli isolates in South Africa

A series of colistin-resistant Escherichia coli clinical isolates was recovered from hospitalized and community patients in South Africa. Seven clonally unrelated isolates harbored the mcr-1 gene located on different plasmid backbones. Two distinct plasmids were fully sequenced, and identical 2,600-bp-long DNA sequences defining a mcr-1 cassette were identified. Promoter sequences responsible for the expression of mcr-1, deduced from the precise identification of the +1 transcription start site for mcr- 1, were characterized

Resistance to colistin associated with a single amino acid change in protein PmrB among Klebsiella pneumoniae isolates of worldwide Origin

A series of colistin-resistant Klebsiella pneumoniae isolates recovered from different countries was investigated in order to evaluate the involvement of the PmrA/PmrB two-component system in this resistance. Six isolates possessed a mutated PmrB protein, which is encoded by the pmrB gene, part of the pmrCAB operon involved in lipopolysaccharide modification. The same amino acid substitution (Thr157Pro) in PmrB was identified in the six isolates. The six isolates belonged to four distinct clonal groups, recovered in South Africa (sequence type 14 [ST14]), Turkey (ST101), and Colombia (ST258 and ST15). Three out of the four clones produced a carbapenemase, OXA-181, OXA-48, or KPC-3, while a single isolate did not produce any carbapenemase. Expression assays revealed an overexpression of the pmrA (70-fold), pmrB (70-fold), pmrC (170-fold), and pmrK (40-fold) genes in the pmrB-mutated isolate compared to expression of the pmrB wild-type isogenic K. pneumoniae isolate, confirming that the PmrB substitution was responsible for increased expression levels of those genes. Complementation assays leading to the expression of a wild-type PmrB protein restored the susceptibility to colistin in all isolates, confirming that the substitution in PmrB was responsible for the resistance phenotype. This study identified a key amino acid located in the PmrB protein as being responsible for the overexpression of pmrCAB and pmrHFIJKLM operons, leading to resistance to colistin

Investigation of biofilm formation on a charged intravenous catheter relative to that on a similar but uncharged catheter

Catheter-related blood stream infections increase morbidity, mortality, and costs. This study investigated whether Certofix® protect antimicrobial catheters carry a surface charge and whether this inhibits biofilm formation. The capacitance of the catheter surfaces was measured and, to determine if the catheters released ions, distilled water was passed through and current measured as a function of voltage. With probes touching the inner and outer surfaces, capacitance was not voltage-dependent, indicating surfaces were uncharged or carried a similar charge. When one probe penetrated the catheter wall, capacitance was weakly voltage-dependent, indicating the presence of a surface charge. Standard and charged catheters were also exposed to phosphate buffered saline as controls or 2×106 colony forming units/mL (in phosphate buffered saline) of six different microorganisms for 60 or 120 minutes. When the growth of detached bacteria was measured, biofilm formation was significantly reduced, (P<0.05), for charged catheters for all organisms.B Braun Melsungen AG (Melsungen, Germany) supplied the catheters and sufficient funds to perform the biofilm studies in the form of an unrestricted grant. RC is supported by the National Research Foundation of South Africa. RM is supported by the National Research Foundation (SA) under the Nanotechnology Flagship Project grant and the University Research Council (Witwatersrand)http://www.dovepress.com/medical-devices-evidence-and-research-journalhb201

Antimicrobial susceptibility profile of selected bacteraemic pathogens from private institutions in South Africa

Objectives. The National Antimicrobial Surveillance Forum is a continuous  surveillance organisation comprising all academic/ public and private   sector  laboratories in South Africa.Methods. The antibiotic susceptibility of blood culture isolates of  Escherichia  coli, Klebsiella pneumoniae, Enterobacter species,   Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus  aureus from patients in private hospitals in five major centres were  investigated. Antimicrobial susceptibility tests were performed by 12  participating laboratories  according to the Clinical and Laboratory Standards Institute (CLSI)  guidelines. Extended-spectrum 13-lactamase (ESBL)  production was  determined in selected species of Enterobacteriaceae  irrespective of source.Results. The overall prevalence of ampicillin resistance in blood culture isolates of E. coli (N = 471) was 84%, and 20% were resistant to the  fluoroquinolones. Considerable geographical differences were noted   between the centres with regard to the K. pneumoniae (N = 636) resistance rates for ceftriaxone and/ or cefotaxime (39- 87%). The most active   agents in the Enterobacter spp. (N = 244) were imipenem/meropenem, ertapenem, ciprofloxacin, levofloxacin and cefepime, with 100%,94%, 88%, 87% and 80% susceptibility, respectively. Carbapenem resistance in P. aeruginosa (N = 382) varied between 42% and 45%, and in the case of A. baumannii (N= 190) resistance varied between 32% and 33% for   meropenem and imipenem respectively. The nationwide incidence of  oxacillin resistance in S. aureus (N = 629) was 36%. Overall, the  prevalence of ESBL production among all isolates of K. pneumoniae was 26% (N = 7 514), while in Enterobacter spp. it was 12% (N = 4 031) and in E. coli 5% (N = 28 412).Conclusions. The data highlight the widespread problem of antibiotic  resistance among important bacteraemic pathogens in private institutions in South Africa. Continued surveillance is vital to guide appropriate  empirical therapy for invasive infections

Emergence of plasmid-mediated colistin resistance (MCR-1) among Escherichia coli isolated from South African patients

The polymyxin antibiotic colistin is an antibiotic of last resort for the treatment of extensively drug-resistant Gram-negative bacteria, including carbapenemase- producing Enterobacteriaceae. The State of the World’s Antibiotics report in 2015 highlighted South Africa (SA)’s increasing incidence of these ‘superbugs’ (3.2% of Klebsiella pneumoniae reported from SA were carbapenemase producers), and in doing so, underscored SA’s increasing reliance on colistin as a last line of defence. Colistin resistance effectively renders such increasingly common infections untreatable

Heteroresistance to colistin in Klebsiella pneumoniae associated with alterations in the PhoPQ regulatory system

A multidrug-resistant Klebsiella pneumoniae isolate exhibiting heteroresistance to colistin was investigated. The colistin-resistant subpopulation harbored a single amino acid change (Asp191Tyr) in protein PhoP, which is part of the PhoPQ two-component system that activates pmrHFIJKLM expression responsible for l-aminoarabinose synthesis and polymyxin resistance. Complementation assays with a wild-type phoP gene restored full susceptibility to colistin. Then, analysis of the colistin-susceptible subpopulation showed a partial deletion (25 bp) in the phoP gene compared to that in the colistin-resistant subpopulation. That deletion disrupted the reading frame of phoP, leading to a longer and inactive protein (255 versus 223 amino acids long). This is the first report showing the involvement of mutation(s) in PhoP in colistin resistance. Furthermore, this is the first study to decipher the mechanisms leading to colistin heteroresistance in K. pneumoniae