Colistin For Treatment Research Articles

Ventilator-Associated Pneumonia Caused by Multidrug-Resistant Gram-Negative Bacteria in Vietnam: Antibiotic Resistance, Treatment Outcomes, and Colistin-Associated Adverse Effects.

Background: Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) gram-negative bacteria (GNB) presents a serious clinical scenario, and there is disagreement regarding the role of colistin in treatment. This study aimed to characterize the antibiotic resistance of MDR GNB and evaluate the treatment outcomes and side effects of colistin in VAP patients caused by MDR GNB, particularly in Vietnam. Methods: A prospective cohort research was undertaken. We enrolled 136 intubated patients diagnosed with VAP according to the Centers for Disease Control and Prevention (CDC) 2019. Sixty-six individuals with an isolated gram-negative bacterium (Acinetobacter baumannii, Klebsiella pneumoniae, or Pseudomonas aeruginosa) satisfied the European Centre for Disease Prevention and Control (ECDC)’s criteria for multi-antibiotic resistance. Results: GNB resistance was categorized as 10.6% MDR, 63.6% XDR, and 25.8% PDR. GNB were resistant to β-lactams 80–100%, aminoglycosides 50–86.7%, fluoroquinolones 100% and colistin 2.8–20%. The 28-day mortality rate was 54.5%, and acute kidney injury occurred at 12.1%. There was no statistically significant difference in mortality rate between groups receiving regimens with or without colistin (58.3% and 73.3%, respectively; OR = 1.964; 95%CI 0.483–7.989). Neither was there a statistically significant difference in acute renal damage rate between groups receiving regimens with or without colistin (14.3% and 9.7%, respectively; OR = 1.556; 95%CI 0.34–7.121). Conclusions: GNB had a high rate of antibiotic resistance to most antibiotics. The addition of colistin to the medication did not show significant differences in renal toxicity or mortality, while colistin resistance was relatively low; larger studies need to be conducted.

Cost-Effectiveness of Imipenem/Cilastatin/Relebactam Compared with Colistin in Treatment of Gram-Negative Infections Caused by Carbapenem-Non-Susceptible Organisms.

IntroductionImipenem/cilastatin/relebactam (IMI/REL), a combination β-lactam antibiotic (imipenem) with a novel β-lactamase inhibitor (relebactam), is an efficacious and well-tolerated option for the treatment of hospitalized patients with gram-negative (GN) bacterial infections caused by carbapenem-non-susceptible (CNS) pathogens. This study examines cost-effectiveness of IMI/REL vs. colistin plus imipenem (CMS + IMI) for the treatment of infection(s) caused by confirmed CNS pathogens.MethodsWe developed an economic model comprised of a decision-tree depicting initial hospitalization, and a Markov model projecting long-term health and economic impacts following discharge. The decision tree, informed by clinical data from RESTORE-IMI 1 trial, modeled clinical outcomes (mortality, cure rate, and adverse events including nephrotoxicity) in the two comparison scenarios of IMI/REL versus CMS + IMI for patients with CNS GN infection. Subsequently, a Markov model translated these hospitalization stage outcomes (i.e., death or uncured infection) to long-term consequences such as quality-adjusted life years (QALYs). Sensitivity analyses were conducted to test the model robustness.ResultsIMI/REL compared to CMS + IMI demonstrated a higher cure rate (79.0% vs. 52.0%), lower mortality (15.2% vs. 39.0%), and reduced nephrotoxicity (14.6% vs. 56.4%). On average a patient treated with IMI/REL vs. CMS + IMI gained additional 3.7 QALYs over a lifetime. Higher drug acquisition costs for IMI/REL were offset by shorter hospital length of stay and lower AE-related costs, which result in net savings of $11,015 per patient. Sensitivity analyses suggested that IMI/REL has a high likelihood (greater than 95%) of being cost-effective at a US willingness-to-pay threshold of $100,000–150,000 per QALY.ConclusionsFor patients with confirmed CNS GN infection, IMI/REL could yield favorable clinical outcomes and may be cost-saving—as the higher IMI/REL drug acquisition cost is offset by reduced nephrotoxicity-related cost—for the US payer compared to CMS + IMI.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00607-x.

Comparative genome analysis of colistin-resistant OXA-48-producing Klebsiellapneumoniae clinical strains isolated from two Iranian hospitals

BackgroundCarbapenemase-producing Klebsiella pneumoniae (CP-KP) is becoming extensively disseminated in Iranian medical centers. Colistin is among the few agents that retains its activity against CP-KP. However, the administration of colistin for treatment of carbapenem-resistant infections has increased resistance against this antibiotic. Therefore, the identification of genetic background of co-carbapenem, colistin-resistance K.pneumoniae (Co-CCRKp) is urgent for implementation of serious infection control strategies.MethodsFourteen Co-CCRKp strains obtained from routine microbiological examinations were subjected to molecular analysis of antimicrobial resistance (AMR) using whole genome sequencing (WGS).ResultsNine of 14 K.pneumoniae strains belonged to sequence type (ST)-11 and 50% of the isolates had K-locus type 15. All strains carried blaOXA-48 except for P26. blaNDM-1 was detected in only two plasmids associated with P6 and P26 strains belonging to incompatibility (Inc) groups; IncFIB, IncHI1B and IncFII. No blaKPC, blaVIM and blaIMP were identified. Multi-drug resistant (MDR) conjugative plasmids were identified in strains P6, P31, P35, P38 and P40. MICcolistin of K. pneumoniae strains ranged from 4 to 32 µg/ml. Modification of PmrA, PmrB, PhoQ, RamA and CrrB regulators as well as MgrB was identified as the mechanism of colistin resistance in our isolates. Single amino acid polymorphysims (SAPs) in PhoQ (D150G) and PmrB (R256G) were identified in all strains except for P35 and P38. CrrB was absent in P37 and modified in P7 (A200E). Insertion of ISKpn72 (P32), establishment of stop codon (Q30*) (P35 and P38), nucleotides deletion (P37), and amino acid substitution at position 28 were identified in MgrB (P33 and P42). None of the isolates were positive for plasmid-mediated colistin resistance (mcr) genes. P35 and P38 strains carried iutA, iucD, iucC, iucB and iucA genes and are considered as MDR-hypervirulent strains. P6, P7 and P43 had ICEKp4 variant and ICEKp3 was identified in 78% of the strains with specific carriage in ST11.ConclusionIn our study, different genetic modifications in chromosomal coding regions of some regulator genes resulted in phenotypic resistance to colistin. However, the extra-chromosomal colistin resistance through mcr genes was not detected. Continuous genomic investigations need to be conducted to accurately depict the status of colistin resistance in clinical settings.

Intravenous vs intravenous plus aerosolized colistin for treatment of ventilator-associated pneumonia – a matched case–control study in neonates

ABSTRACT Background Recently intravenous (IV) and aerosolized (ASZ) colistin have been used for treating ventilator-associated pneumonia (VAP) due to colistin susceptible multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin has limited lung penetration. We compared the efficacy and safety of IV-alone versus IV+ASZ-colistin for treating VAP in neonates. Methods This retrospective matched case–control study was performed at NICU of the Aga Khan University Hospital, Pakistan between January 2015 and December 2018. Sixteen neonates with MDR-GNB associated VAP received IV-ASZ-colistin and were matched for date of birth, gestational age, birth weight, Apgar score, antenatal steroid history, disease severity, and duration of mechanical ventilation with 16 control neonates who received IV-colistin alone. Results Both groups had similar MDR-GNB isolates and Acinetobacter baumannii (78%) was the most common pathogen. No colistin-resistant strain was isolated. Duration of IV-colistin and concomitant antibiotics use was significantly (p < 0.05) shorter in the IV-ASZ-colistin group. Significantly (p < 0.05) higher clinical cure and microbial eradication, along with lower ventilatory requirements, mortality rate, and colistin induced nephrotoxicity and electrolyte imbalance was observed in the IV-ASZ-colistin group. Conclusions With better lung penetration, ASZ-colistin offers effective and safe microbiological and clinical benefits as adjunctive or alternate treatment of VAP due to colistin susceptible MDR-GNB in neonates.

Comparison of antibacterial activities of polymyxin B and colistin against multidrug resistant Gram negative bacteria

Background: Polymyxin B and colistin have similar structures except for one amino acid. Usually, physicians choose either polymyxin B or colistin for treatment of infections caused by multidrug-resistant (MDR) organisms. The preference is based on previous experience. Not much data are found in the literature comparing the two drugs against the same microorganisms. In this study, we compared in vitro antimicrobial activities of the two polymyxins against a panel of highly resistant and susceptible microorganisms.Methods: Eighty-nine clinical isolates (27 Klebsiella pneumoniae, 31 Acinetobacter baumannii and 31 Pseudomonas aeruginosa) were tested in broth microdilution assays. Time-kill curve experiments were carried out on selected isolates.Results: Significantly lower MICs for polymyxin B than for colistin were found against all species tested including K. pneumoniae (p < .02), A. baumannii (p < .001) and P. aeruginosa (p < .01). The low MICs caused a change in categorical interpretations of only two K. pneumoniae and two P. aeruginosa. Similar results were obtained in time-kill curve experiments with both susceptible and resistant clinical isolates.Conclusions: Significantly lower MICs were found for polymyxin B against three of the most critical MDR species. Even though differences in categorical interpretations were not striking, lower MICs might be a critical consideration in clinical management of select cases where the concentration of these toxic antibiotics matters because of underlying co-morbidities. These results provide support to previous suggestions that re-consideration of breakpoint interpretations for polymyxins might be needed.

High carriage rate of mcr-1 and antimicrobial resistance profiles of mcr-1-positive Escherichia coli isolates in swine faecal samples collected from eighteen provinces in China

The mcr-1 gene is a plasmid-borne and globally distributed colistin-resistance gene, which threatens the last-line role of colistin in treatment of infections caused by multi-drug resistant(MDR) Gram-negative bacteria in humans. The aim of this study was to obtain a comprehensive understanding of mcr-1 prevalence in the pig industry in China. A total of 600 faecal samples were collected from 60 swine farms in 18 provinces of China. Faecal DNA was extracted and subjected to PCR screening to detect the presence of mcr-1. Positive samples were randomly selected for isolation of colistin-resistant bacteria. A total of 152 mcr-1-positive isolates collected from different provinces were characterized by antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE) typing. Extremely high rate of faecal carriage of mcr-1(457/600, 76.2%) was observed, with positive rates ranging from 45.0%–100% among the provinces. All colistin-resistant colonies were identified as Escherichia coli and mcr-1-positive. The 152 representative mcr-1-positive E. coli isolates showed high level resistance to ampicillin (79.60%), tetracycline(94.74%), doxycycline(93.42%), florfenicol(78.29%), enrofloxacin(44.08%), and ciprofloxacin(38.82%) and low level resistance to ceftiofur(26.32%), cefoxitin(0.66%), and amikacin(0.66%). No resistant isolates were detected for gentamicin, meropenem, and tigecycline. The mcr-1-positive E. coli strains exhibited highly diverse PFGE patterns, which suggested that horizontal transfer through plasmids or other mobile elements was the main mechanism for the wide dissemination of mcr-1 in pig farms. Similar studies are warranted to continuously monitor colistin resistance and mcr-1 prevalence in food-animal production.

The evaluation of safety and efficacy of colistin use in pediatric intensive care unit: Results from two reference hospitals and review of literature.

Colistin, an old cationic polypeptide antibiotic, have been reused due to rising incidence of infections caused by multi-drug resistant (MDR) Gram-negative microorganisms and the lack of new antibiotics. Therefore, we evaluated safety and efficacy of colistin in treatment of these infections. This study included 104 critically ill children with a median age of 55,9 months between January 2011 and January 2016. Nephrotoxicity occurred in 11 (10.5%) patients. Nephrotoxicity occurred between the third and seventh day of treatment in 63% of colistin induced nephrotoxicity episodes. The subgroup analysis between the patients who developed nephrotoxicity during colistin treatment and those that did not, showed no significant difference in terms of age, underlying disease, cause for PICU admission and type of infection required colistin treatment, P values were 0.615, 0.762, 0.621, 0.803, respectively. All patients were receiving a concomitant nephrotoxic agent (P= 0,355). The majority of the patients (52%) were having primary or secondary immune deficiency in treatment failure group and the most common cause of PICU admission was sepsis in treatment failure group, P values were 0.007 and 0.045, respectively. Mortality attributed to colistin failure and crude mortality were 14.4% and 29.8%, respectively. In conclusion, colistin may have a role in the treatment of infections caused by multidrug-resistant Gram-negative bacteria in critically ill children. However, the patients have to be followed for side effects throughout colistin treatment, not for only early stage. And the clinicians should be aware of increase in the rate of nephrotoxicity in patients those have been receiving a concomitant nephrotoxic agent.

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.

Clinical outcomes and safety of colistin in treatment of gram negative infections: A prospective observational study

BackgroundDespite the fact that colistin has a significant activity against MDR gram-negative organisms, its toxicity limits its use. However, the limited therapeutic options due to increasing antibiotic resistance have made re-evaluation of older antibiotics inevitable. In contrast, lack of data to guide the usage of these drugs demands for studies on their safety and efficacy. This studies the clinical outcomes and safety of colistin at a tertiary care centre in Mumbai. Materials and methodsA prospective observational study was conducted at P.D. Hinduja Hospital, Mumbai for a period of seven months. Diagnosis of infection was based on CDC guidelines and APACHE II score was used to assess the severity of illness. Clinical and microbiological response to colistin was evaluated along with the incidence of nephrotoxicity (RIFLE criteria) and neurotoxicity. ResultsSixty-two patients (median age 56years, with documented gram negative bacterial infection and mean APACHE II score 22) received colistin. Clinically favourable response was seen in 71% patients. However, the mortality among the study population was 27%. Univariate analysis identified pneumonia and ICU admission as independent factors for adverse outcome. Deterioration of renal function was observed in 35.89% as per RIFLE criteria. 6 (9.6%) patients demonstrated neurotoxicity. ConclusionColistin is effective in treatment of gram negative infections and its use should be reappraised. However since colistin is the last resort it is imperative to make its best use to ensure that it remains as a safe and effective mode of treatment when need be.

Nebulized colistin for treatment of ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: we still need to straighten out the dose!

We applaud the extensive systematic review and meta-analysis by Zampieri and colleagues on inhaled antibiotics for ventilator-associated pneumonia (VAP) [1] but would like to add some comments regarding inhaled colistin for treatment of VAP caused by multidrug-resistant Gram-negative bacteria (MDR-GNB). In patients with cystic fibrosis, the equivalent of 160 mg colistimethate sodium (CMS) produced high and therapeutic endobronchial concentrations [2]. However, to be effective in VAP caused by MDR-GNB, colistin must attain pulmonary concentrations that substantially exceed minimal plasma inhibitory levels for these microorganisms. Colistin aerosols used in the predominantly retrospective and observational studies summarized by Zampieri and colleagues contained CMS doses ranging from 80 to 300 mg [1]. These doses may be insufficient to grant any significant or additional therapeutic value to inhaled colistin, especially when used together with intravenous antibiotics. Indeed, a total daily inhaled dose of 240 mg CMS was found to be inadequate to treat lung infection caused by MDR-GNB [3]. A recent review recommended inhalation of 160 mg CMS every 8 h for severe pulmonary infections [4]. Finally, a daily dose of 1,200 mg inhaled CMS used in monotherapy or associated with a 3-day course of intravenous aminoglycosides cured VAP caused by MDR-GNB as effectively as VAP caused by β-lactam susceptible GNB [5]. In contrast with intravenous administration, high doses of nebulized colistin are not associated with an increased risk of kidney injury, even when given for a prolonged period of time [5]. We strongly salute aerosolized colistin as an important alternative or adjunct therapy to treat VAP caused by MDR-GNB, provided that the daily inhaled dose is sufficiently high.

High-dose colistin for microbiologically documented serious respiratory infections associated with carbapenem-resistant Acinetobacter baummannii in critically ill cancer patients: a retrospective cohort study

Background: Recent studies suggested that high doses of colistin are necessary in the treatment of serious infections. However, few studies have evaluated such treatment. The objective of this study was to evaluate the effectiveness and nephrotoxicity of high-dose colistin in critically ill patients with respiratory infections associated with carbapenem-resistant Acinetobacter baumannii (CRAB). Methods: This was a retrospective cohort study of critically ill cancer patients who received high-dose intravenous colistin for treatment of CRAB-related respiratory infections. Patients received colistimethate sodium 9 million IU/day or an equivalent dose, adjusted for renal function. Treatment effectiveness was evaluated by determining the microbiological clearance, recurrent and new CRAB-related infections, and mortality in the intensive care unit (ICU). Nephrotoxicity was defined according to the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria. Results: A total of 89 patients met the inclusion criteria. Microbiological clearance was observed in 51 (66.2%) subjects who had at least 2 follow-up cultures (n = 77). In patients who achieved microbiological clearance, recurrent and new CRAB-related infections occurred in 3 (5.9%) and 9 (17.6%) subjects, respectively. Fifty-seven patients (64%) died in the ICU. Thirty-five (39.3%) subjects developed nephrotoxicity according to the RIFLE criteria, which was classified as risk in 4 (11.4%) subjects, injury in 8 (22.8%) subjects, and failure in 21 (60%) subjects. Conclusions: In critically ill cancer patients, high-dose colistin was associated with microbiological clearance in about two-thirds of the subjects with CRAB-related respiratory infections but mortality was high. A significant portion of patients developed nephrotoxicity while receiving colistin therapy.

Effectiveness of Adjunctive Inhaled Colistin in Treatment of Ventilator Associated Pneumonia

Ventilator-Associated pneumonia (VAP) represents a major health problem in mechanically ventilated patients in intensive care units (ICUs). Aerosolized colistin could represent an adjunctive treatment to intravenous antibiotics in VAP. To evaluate the safety and efficacy of adjunctive inhaled colistin in treatment of patients with Gram-negative VAP compared to the conventional intravenous antibiotic regimen alone. This prospective randomized controlled study was conducted from July 2013 to August 2014 at Kasr El-Aini Medical ICU. Our study included a total number of 50 cases with VAP randomly assigned into two equal groups; a study group (who received the conventional systemic IV antibiotic regimen plus adjunctive inhaled colistin) and a control group (who received the conventional systemic IV antibiotic regimen alone). 76% of the patients were men with severe underlying co-morbidities. The main causative organisms of VAP were Klebsiella spp. (32%), Acinetobacter spp. (26%) and Pseudomonas spp. (24%). Patients in the study group had significantly more favourable microbiological outcome when compared with patients in the control group (80% versus 52%, P=0.03). No adverse effects related to inhaled colistin (nephrotoxicity, neurotoxicity, bronchoconstriction, cough, apnea or chest tightness) were recorded. Inhaled colistin seems to be safe and efficient as an adjunctive treatment for patients with Gram-negative VAP.

Colistin therapy for multidrug-resistant Gram-negative infection: clinical outcome and risk factors

Multidrug-resistant (MDR) Gram-negative bacterial infection is widespread all over the world, and recently it led to the reintroduction of colistin for treatment of MDR Pseudomonas aeruginosa and Acinetobacter spp. infection [1]. According to the 2007 European antimicrobial resistance surveillance system (EARSS) consisting of 33 European countries, six countries reported carbapenem resistance rates higher than 25 % among P. aeruginosa isolates [2]. The rate of imipenem-resistant Acinetobacter reached up to 51 % in Korea according to the report of the Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR) [3]. Polymyxin E (colistin) that was developed in the 1940s is still the principal therapeutic agent for MDR Gram-negative pathogens. Because of the nephrotoxicity and neurotoxicity of colistin, it was not used for a long time [4]. Colistin has lately been considered for MDR treatment due to the emergence of MDR bacteria. However, the efficacy test results of colistin have been quite controversial. Most studies have been retrospective, and the clinical data analysis has been done without control groups [5, 6]. In this study, we evaluated the clinical efficacy of colistin in MDR bacterial infection. We conducted a retrospective hospital-based cohort study at an 850-bed hospital by reviewing the medical records of patients who received intravenous colistin for MDR bacterial infection from May 2007 to December 2010. Demographics, clinical presentation, causative organism, and outcomes were recorded. Patients were excluded if they received colistin treatment for \72 h and were under the age of 18. Types of infection were evaluated, following the United States Centers for Disease Control and Prevention (CDC) criteria. Recent invasive procedure was defined as preceding an invasive procedure within 48 h, including arterial, central venous catheter, urinary catheter, or applying mechanical ventilation before the culture results of MDR infection. MDR bacteria were defined to be resistant to all antibiotic agents such as penicillins, aminoglycosides, ampicillin/sulbactam, cephalosporins, aztreonam, carbapenems, fluoroquinolones, and tetracyclines, except colistin. Interpretation of susceptibility results was carried out according to the current Clinical and Laboratory Standards Institute guidelines. A total of 107 patients were enrolled in this study, and their demographic and clinical data are summarized in Table 1. Sixty-six patients (61.7 %) were over 64 years, and 36 patients (33.6 %) had a hospital stay of more than 125 days before MDR bacteria culture. Common underlying diseases were hypertension (63.5 %), diabetes (34.6 %), chronic obstructive pulmonary disease (24.3 %), cancer (19.6 %), chronic renal failure (CRF), and end-stage renal disease (ESRD; 12.1 % for both CRF and ESRD). More than 95 % of colistin therapy took place in ICUs. Cerebrovascular event (27.1 %) including cerebral infarction or hemorrhage was the most common cause of admission. We evaluated the clinical and microbiological responses both to colistin and to previously exposed antibiotics combined with colistin. Efficacy was evaluated as both clinical and bacteriological responses. After 3 days of colistin therapy, clinical improvement was graded as a good or poor clinical response. A good responder was defined as a patient whose symptoms were improved with bacteriologically clear pathogen within 1 week. Baseline characteristics and various risk factors were compared Y. H. Jun S. J. Jeun S. H. Kang H. J. Choi (&) Division of Infectious Disease, Department of Internal Medicine, Ewha Womans University, Mokdong Hospital, 911-1 MokDong, Yangcheon-Ku, Seoul, Korea e-mail: heechoi@ewha.ac.kr

Nebulized Colistin for the Treatment of Multidrug-Resistant Gram-Negative Pneumonia

Purpose To describe the use of nebulized colistin (colistimethate sodium) for the treatment of multidrug-resistant gram-negative infections. Specific aims were to identify dose and frequency of nebulized colistin therapy currently used, to assess clinical and microbiological efficacy, and to assess the prevalence of adverse events resulting from colistin therapy. Methods A retrospective chart review was performed at a tertiary care, level I trauma center and teaching hospital. The review included examination of 29 courses of colistin therapy administered to 24 adults receiving at least 24 hours of nebulized colistin for the treatment of gram-negative pneumonia. Results Demographic, medication, adverse event, and outcome data were collected for the duration of colistin therapy. Colistin was administered to patients with multidrug-resistant infections caused by gram-negative organisms. Many patients had a history of exposure to multiple antibiotics or drug allergies. Resistance to colistin was observed in 3 of 18 isolates with available susceptibility data. Determining the prevalence of adverse events was difficult because of the use of multiple medications. Many patients had missed antibiotic doses. A 25% mortality rate was observed. Conclusion The findings of this study serve to demonstrate the use of nebulized colistin for treatment of multidrug-resistant gram-negative pneumonia in patients without cystic fibrosis; to raise concern with regard to the large number of missed antibiotic doses; and to emphasize the need for further investigation by a larger, prospective, randomized trial.

203 Experiences from 15 years use of inhaled colistin in treatment of P. aeruginosa in a CF-clinic

203 Experiences from 15 years use of inhaled colistin in treatment of P. aeruginosa in a CF-clinic