Introduction: The increasing trend of extensively drugresistant gram negative bacteria responsible for nosocomial infections has prompted resurgence colistin usage. Colistin-induced nephrotoxicity is a concern with disparity in the reported rates between previous studies. This study aims to evaluate colistin-induced nephrotoxicity among Malaysian population. Methods: The medical records of ICU patients receiving colistin therapy in Hospital Serdang and Hospital Sungai Buloh from 2010 to 2012 were retrospectively reviewed. Demographics data, treatment characteristic as well as culture result and creatinine level were documented. Nephrotoxicity was determined based on RIFLE criteria. Results: A total of 100 patients were included. Median daily dose, cumulative dose and duration of colistin therapy were 3.0 MIU (IQR: 4, range 1-12), 17.8 MIU (IQR: 31.5, range 2-180) and seven days (IQR: 4, range 1-30). Nephrotoxicity was found in 23% of the study population. All cases were reversible but marginally associated with higher mortality. No statistical association exist between age, gender and race as well as administration routes with nephrotoxicity by univariable analysis. The association of dose and duration with nephrotoxicity was also not significant by univariable analysis. After adjustment for confounders, statistical association between the independent variables and dependent variable remains not significant. Conclusion: Lower dose and shorter duration in local settings contribute to lack of association between colistin therapy and nephrotoxicity in this study. Higher dosing regimen with loading dose application has been introduced in the latest National Antibiotic Guideline. Further evaluation of colistin-induced nephrotoxicity and potential risk factors is therefore warranted.
Colistin ; Intensive Care Units

Introduction: The increasing trend of extensively drug-resistant gram-negative infections led to the reconsideration of colistin as a valuable therapeutic option. Objectives: To describe the clinical profile and treatment response of children with extensively drug resistant (XDR) Gram-negative infections given colistin versus other antimicrobials. Methods: This retrospective descriptive study involved patients treated for XDR Gram-negative infections from January 2014 to June 2017 in a tertiary hospital in Metro Manila. Descriptive statistics were used to summarize clinical characteristics of subjects. Treatment response to colistin versus other antimicrobial agents were compared in terms of success, failure, and toxicity. The Fisher-exact and Mann Whitney U tests were used to assess statistical differences between the colistin and non-colistin groups. Results: Majority of patients with XDR Gramnegative infections had previous antibiotic exposure. More patients in the colistin group received TPN 43.2% vs 23.7% (p=0.035), had a longer hospital stay prior to the onset of XDR Gram-negative infection, 27 days vs. 15.5 days (p=0.001), and had a longer total hospital stay with a median of 52 days vs 30 days (p < 0.001). Treatment success was significantly higher in the colistin group at 70.3%, as against 46.5% in the non-colistin group (p=0.014). There was no difference in the treatment duration of both groups. The colistin group had longer time to clinical response, with a mean of 6.27 (+ 3.57) days compared with those from the non-colistin group, with a mean of 4.36 (+ 1.77)(p=0.008). The colistin group had more fungal infections during the course of treatment (p=0.001). Conclusion Based on our institutional experience, colistin is considered relatively effective and safe in treating XDR Gram-negative infections in children.
Cross Infection ; Colistin

Background: The global burden of multi-drug resistant gram-negative bacterial (MDR-GNB) infections has been increasing. Neonates are at a particularly high-risk and there is limited treatment option. The use of colistin has been re-introduced for this population. However, data on its use in neonates is scarce. Objectives: To determine the effectiveness and adverse effects of intravenous colistin in neonates with multidrug-resistant gram-negative infections. Design: This is a retrospective cohort study of the clinical profile and outcome of neonates with MDR-GNB infections given colistin for a minimum of 3 days conducted from April 2015 to April 2019. Results: A total of 175 pediatric patients had MDR-GNB infections. 75 (43%) neonates met the inclusion criteri a and received intravenous colistin. Of the 75 patients with MDRGNB infections- that included sepsis, pneumonia, urinary tract infection and abscess, 37 (49.3%) were alive and 38 (50.7%) patients died. Nephrotoxicity was seen in 4% if patients and 2.6% patients had hypersensitivity reaction. MDROs isolated were Acinetobacter baumanii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Conclusions Intravenous colistin is 50% effective and is relatively safe to use in neonates.
Colistin ; Infant, Newborn

The current strategy in treating multi-drug resistant gram-negative bacterial (MDR-GNB) infections is salvage therapy by using polymyxins. However, the beginning emergence of polymyxin resistance should enforce strict antimicrobial stewardship programs to preserve polymyxin efficacy. Knowledge of structural characteristics, pharmacodynamic, and pharmacokinetic profiles of polymyxins, as well as consideration of efficacy, safety, suitability, and cost, will help in the choice of the appropriate polymyxin for therapy. Polymyxin B is the recommended polymyxin for systemic use, while colistin is recommended for lower urinary tract infections, intraventricular, and intrathecal use. Either polymyxin can be used for hospital-acquired and ventilator-associated pneumonia. Combination therapy over monotherapy remains to be advantageous due to synergism and decreased resistance development. The choice of the second drug to be used should be based on full susceptibility, or if unavailable, a drug with the least minimum inhibitory concentration relative to the breakpoint set by the Clinical and Laboratory Standards Institute. Using the mnemonic ESCAPE can also guide physicians in their polymyxin prescription process: (1) Checking if the pathogen is Extensively resistant or multi-drug resistant; (2) checking the patient’s clinical status if compatible with Significant infection; (3) using Combination therapy; (4) ensuring Adequate dosing; (5) Proper preparation and administration of drug; and (6) keeping an Eye for response and adverse effects.
Polymyxin B ; Colistin ; Polymyxins

No abstract available.
Acinetobacter baumannii ; Acinetobacter ; Colistin ; Solanum tuberosum

We identified ISAba15 inserted into the carO gene in an Acinetobacter baumannii isolate. The insert disrupted the lpxD gene, resulting in colistin resistance in A. baumannii. Persistence in carbapenem resistance in A. baumannii isolates with an intact carO gene indicates that loss of the encoded CarO may play a minor role in carbapenem resistance.
Acinetobacter baumannii* ; Colistin ; Drug Resistance, Bacterial ; Membrane Proteins*

Acinetobacter species is a non-fermentative aerobic gram-negative coccobacillus that is an important pathogen found in nosocomial infections. Recently, multi-drug resistant Acinetobacter baumannii (MDR-AB) infections have been increasing and pose a serious problem. Most such infections present as bacteremia, pneumonia, or a wound infection; however, CNS infections are very rare. We herein present a case of ventriculitis caused by MDR-AB in a 37-year old man after a neurosurgical intervention. The patient was successfully treated with intrathecal colistimethate.
Acinetobacter ; Acinetobacter baumannii ; Bacteremia ; Colistin ; Cross Infection ; Humans ; Pneumonia

BACKGROUND: Multi-drug resistant (MDR) Acinetobacter baumannii has emerged as one of the most important nosocomial pathogens. In addition to the diverse resistance mechanisms, some A. baumannii strains are known to have biofilm-producing capacity, thereby decreasing antibiotic effectiveness. MATERIALS AND METHODS: This study was designed to assess biofilm-producing capacity of three different MDR A. baumannii strains with diverse resistance mechanisms (OXA-51, IMP-1 and VIM-2 type beta-lactamases), and intended to compare the effect of each antibiotic regimen (rifampicin, colistin, imipenem, tigecycline, rifampicin-imipenem and rifampicin-colistin) on mature A. baumannii biofilms using in vitro polystyrene plate biofilm assay. RESULTS: Among three MDR A. baumannii strains, only VIM-2 strain produced strong biofilm compared to the controls (optical density, 8.04 +/- 2.16 vs. 0.49 +/- 0.26). Regarding VIM-2 strains, none of imipenem, colistin and rifampicin reduced biofilm formation alone at MIC of each antibiotic agent (inhibition of biofilm synthesis, less than 30%). In comparison, tigecyclin (0.76 +/- 0.23), imipenem-rifampicin (1.07 +/- 0.31) and colistin-rifampicin (1.47 +/- 0.54) showed a significant inhibition of biofilm synthesis compared to the positive controls at 48 hours after incubation (P<0.01). Tigecycline inhibited biofilm formation even at the one fourth level of MIC (1.17 +/- 0.21). Likewise, both imipenem and colistin were also effective even with the reduced concentrations when those were combined with rifampicin. Such biofilm-inhibiting effects with those antibiotic regimens sustained up to 96 hours after incubation. CONCLUSION: Tigecycline, imipenem-rifampicin and colistin-rifampicin would be effective for the prevention or reduction of biofilm formation caused by A. baumannii strains.
Acinetobacter baumannii* ; Anti-Bacterial Agents ; Biofilms ; Colistin* ; Imipenem* ; Polystyrenes ; Rifampin*

Acinetobacter species is a non-fermentative aerobic gram-negative coccobacillus that is an important pathogen found in nosocomial infections. Recently, multi-drug resistant Acinetobacter baumannii (MDR-AB) infections have been increasing and pose a serious problem. Most such infections present as bacteremia, pneumonia, or a wound infection; however, CNS infections are very rare. We herein present a case of ventriculitis caused by MDR-AB in a 37-year old man after a neurosurgical intervention. The patient was successfully treated with intrathecal colistimethate.
Acinetobacter ; Acinetobacter baumannii ; Bacteremia ; Colistin ; Cross Infection ; Humans ; Pneumonia

Rapidly increasing antimicrobial resistance and lack of effective antibiotics are dilemma in the treatment of infectious diseases. Clinicians are now considering the use of old antibiotics such as colistin, fosfomycin because of limitation of therapeutic options. The unique pharmacokinetic and pharmacodynamics properties of these antibiotics have led the new therapeutic approaches, such as the combination of agents and newer dosing regimens. Colistin has become the last drug of the treatment of multidrug resistant gram-negative bacteria and the loading dose and high dose maintenance has been suggested. Tigecycline is licensed for the treatment of complicated skin and intra-abdominal infections and has broad activity against gram-positive and gram-negative pathogens but cautious use in the treatment of bloodstream infection and pneumonia is recommended. Oral and intravenous fosfomycin may be effective treatment options in the case of resistant gram-negative infections but clinical studies are limited.
Anti-Bacterial Agents ; Bacteria* ; Colistin ; Communicable Diseases ; Fosfomycin ; Gram-Negative Bacteria ; Intraabdominal Infections ; Pneumonia ; Skin