Use Of Colistin For Treatment Research Articles

Colistin A Last Resort Antibiotic

Colistin is an antibiotic of last resort, works as a last line of defense against illness caused by the multiple drug resistant (MDR) gram negative bacteria. Polimixins consist of aqua phobic acyl tail, linear tripeptide part, and heptapeptide ring. Chemical formula of colistin is C52H98N16O13. Colistin is given in two forms, colistin methane sulfonate (CMS) and colistin sulfate.
 Findings: Colistin disturbs or destroys the outer membrane of bacteria, or stops the respiratory enzymes of the inner membrane of bacteria. Colistin also works as an antiendotoxin. Colistin has great bactericidal activity against gram negative rods. Colistin resistance is a serious concern of present time. High rate of the spread of MDR gram negative bacterial infections is leading to high use of colistin for treatment, due to which prevalence of colistin resistance is increasing worldwide. As bacterial outer membrane is the main target of colistin, resistance against it develop by modification of outer membrane LPS. There are several mechanisms of colistin resistance. Intrinsic mechanism involves expression of arnBCADTEF operon and eptB gene. Acquired non-transferable resistance involves pmrAB, PhoPQ, and CrrAB two component systems (TCSs), mgrB gene and ramA. Transferable resistance is more serious concern as it can be spread in population by horizontal gene transfer. Mcr genes are responsible for transferable or plasmid-mediated colistin resistance.
 Conclusion: This review focuses on the chemistry of colistin, mechanism of action, spectrum of action, colistin resistance and different mechanisms behind it.

Aztreonam plus ceftazidime-avibactam as treatment of NDM-1-producing Klebsiella pneumoniae bacteraemia in a neutropenic patient: Last resort therapy?

ObjectivesWe report the successful treatment of a bloodstream infection caused by Klebsiella pneumoniae harbouring NDM-1 using aztreonam-ceftazidime-avibactam in a neutropenic patient in whom colistin and meropenem therapy had previously failed. MethodsA clinical isolate was evaluated to determine the presence of NDM, TEM, SHV, CTX, and CMY, and the killing kinetics of aztreonam (ATM; 4 μg/mL), aztreonam-avibactam (ATM-AVI; 4/4 μg/mL), and colistin (2 and 4 μg/mL) were tested. ResultsATM-AVI showed in vitro activity against the Klebsiella pneumoniae harbouring NDM-1, whereas colistin allowed re-growth. ConclusionsThis report supports reconsideration of use of colistin for treatment of infections caused by K. pneumoniae harbouring NDM. CZA/ATM use should be kept in mind as a treatment option, perhaps earlier than colistin.

Intravenous colistin use for infections due to MDR Gram-negative bacilli in critically ill paediatric patients: a systematic review and meta-analysis.

Data are limited regarding the clinical effectiveness and safety of intravenous colistin for treatment of infections due to MDR Gram-negative bacilli (GNB) in paediatric ICUs (PICUs). Systematic review of intravenous colistin use in critically ill paediatric patients with MDR-GNB infection in PubMed, Scopus and EMBASE (up to 31 January 2018). Out of 1181 citations, 7 studies were included on the use of intravenous colistin for 405 patients in PICUs. The majority of patients were diagnosed with lower respiratory tract infections, Acinetobacter baumannii being the predominant pathogen. Colistin dosages ranged between 2.6 and 18 mg/kg/day, with only one case reporting a loading dose. Emergence of colistin resistance during treatment was reported in two cases. Nephrotoxicity and neurotoxicity were reported in 6.1% and 0.5%, respectively, but concomitant medications and severe underlying illness limited our ability to definitively associate use of colistin with nephrotoxicity. Crude mortality was 29.5% (95% CI = 21.7%-38.1%), whereas infection-related mortality was 16.6% (95% CI = 12.2%-21.5%). While the reported incidence of adverse events related to colistin was low, reported mortality rates for infections due to MDR-GNB in PICUs were notable. In addition to severity of disease and comorbidities, inadequate daily dosage and the absence of a loading dose may have contributed to mortality. As the use of colistin for treatment of MDR-GNB infections increases, it is imperative to understand whether optimal dosing of colistin in paediatric patients differs across different age groups. Thus, future studies to establish the pharmacokinetic properties of colistin in different paediatric settings are warranted.

Outbreak of colistin-resistant carbapenemase-producing Klebsiella pneumoniae in Tunisia.

Mechanisms of colistin and carbapenem resistance among a collection of Klebsiella pneumoniae isolates recovered in a university hospital in Tunisia were studied. In vitro antimicrobial susceptibility testing, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blotting and PCR-based replicon typing (PBRT) were performed. Extended-spectrum β-lactamases (ESBLs), carbapenemases, AmpC-type enzymes and mgrB genes were detected by PCR and sequencing. Clonality of isolates was assessed by PFGE and multilocus sequence typing (MLST). Of 940 Enterobacteriaceae isolates recovered from June 2015 to March 2016 in Tahar Sfar Hospital (Mahdia, Tunisia), 220 were identified as K. pneumoniae, among which 29 were carbapenem-resistant. Carbapenem resistance was mostly due to expression of blaOXA-48 or blaOXA-204 in combination with blaCMY-4. Seven isolates carried blaNDM-1, of which two also harboured blaOXA-48, together with blaCMY-16 in one of them. All but two isolates also harboured blaCTX-M-15. All 20 blaOXA-48 genes were part of transposon Tn1999 on an IncL plasmid, whereas blaOXA-204 was found on transposon Tn2016 on an IncA/C plasmid. Finally, all blaNDM-1 genes were located within a Tn125 transposon on an IncFIIk plasmid. Interestingly, 7 (24.1%) of 29 carbapenem-resistant isolates were resistant to colistin, of which 6 were assigned to ST101, had similar PFGE profiles and presented the same 2-kb insertion in the mgrB gene. This study reports, for the first time in Tunisia, the full molecular characterisation of colistin resistance in K. pneumoniae. There is an urgent need for control measures and prudent use of colistin in treatment of infections with carbapenemase-producing K. pneumoniae.