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PubMed1970

Colistin, sulphamethoxazole, and trimethoprim in synergy against Gram-negative bacteria.

The antibacterial activity of the four possible combinations of the three drugs, colistin, sulphamethoxazole, and trimethoprim, has been investigated with Gram-negative bacteria. All of the strains examined, with the exception of the strains of Proteus, were sensitive to colistin. The combination of colistin and sulphamethoxazole was synergic against all 141 sulphamethoxazole-sensitive bacteria out of a total of 164 organisms against which it was tested. The sensitive strains comprised 27 of the 37 Esch. coli, 51 of the 54 Ps. aeruginosa, 24 of the 30 Kl. aerogenes, eight of the 12 shigellae, and all 21 Proteus and 10 salmonellae tested. The combined effect was indifference against the remaining 23 organisms which were resistant to sulphamethoxazole. The combination of colistin and trimethoprim was synergic against all 72 organisms against which it was tested, which comprised 10 Esch. coli, 14 Ps. aeruginosa, 14 Kl. aerogenes, 12 Proteus spp, 10 salmonellae, and 12 shigellae. The combination of sulphamethoxazole and trimethoprim was synergic against 61 of the same 72 organisms; the exceptions were three Esch. coli, four Kl. aerogenes, and four shigellae, all of which were sulphamethoxazole resistant. The combination of all three drugs-colistin, sulphamethoxazole, and trimethoprim-was more active than combinations of any two against 66 of the 72 organisms. The exceptions were three strains of Esch. coli, two of Kl. aerogenes, and one shigella, all of which were sulphamethoxazole resistant.

Bacteria↗
PubMed1997

Effect of tonicity of nebulised colistin on chest tightness and pulmonary function in adults with cystic fibrosis.

BACKGROUND: Inhalation of hypertonic nebulised colistin causes chest tightness and is a reason for discontinuing the treatment. This study examines the relationship of chest tightness and change in lung function in response to the inhalation of a range of tonicities of nebulised colistin and their influence on patients' preference. METHODS: Twenty seven adult patients with cystic fibrosis and a mean forced expiratory volume in one second (FEV1) of 54% predicted (range 24-98) were studied. They inhaled a nebulised solution of hypertonic, isotonic, and hypotonic colistin over three consecutive days in random order in a double blind fashion. Measurements of chest tightness, using a visual analogue scale (VAS), and FEV1 were recorded before and 0, 15, 30, 60, and 90 minutes following inhalation. The solution preferred by each patient was determined at the end of the three days. RESULTS: All tonicities caused a significant fall in FEV1 % predicted and an increase in chest tightness, with no differences between the solutions. However, the mean (SE) time to the maximum fall in FEV1 % predicted was significantly different between the solutions (hypertonic 7.8 (2.1) min, isotonic 19.2 (5.5) min, and hypotonic 34.2 (5.9) min) with a mean difference (95% CI) between hypotonic and hypertonic solutions of 28.04 (14.6 to 41.5) min, between isotonic and hypertonic solutions of 12.0 (-0.1 to 24.1) min, and between hypotonic and isotonic solutions of 15.6 (1.8 to 29.4) min. Positive correlations existed for the maximum fall in FEV1 % predicted between the hypertonic and isotonic solutions (r = 0.62, p < 0.001) and between the hypotonic and isotonic solutions (r = 0.64, p < 0.001). There was no correlation between the objective and subjective measurements for any solution. The patients' preference varied. CONCLUSIONS: All tonicities of colistin caused equal symptoms of chest tightness and reduction in pulmonary function. It is recommended that the patient is challenged with nebulised colistin before prescription of the drug and that the challenge is preceded by an inhaled bronchodilator. Most of the patients preferred the isotonic or hypotonic solutions. The isotonic solution reflects a fall in FEV1 representative of all the solutions. The fall in FEV1 to the hypotonic solution occurred over a longer period and may be better tolerated by some patients.

Administration, Inhalation↗
PubMed1991

Toxicity of colistin in cystic fibrosis patients.

Pulmonary exacerbations of cystic fibrosis associated with strains of Pseudomonas aeruginosa that are resistant to multiple antibiotics are becoming increasingly common. The search for treatment alternatives continues and may include the reexamination of older antibiotics. Colistin sulfate is a polypeptide antibiotic with good activity against P. aeruginosa. Although its use was largely discontinued in the early 1970s because of reports of frequent renal and neurologic toxicity, intravenous colistin is often prescribed at our institution for patients with P. aeruginosa resistant to multiple-drug therapy. We prospectively monitored 19 patients during 21 courses of colistin therapy to identify the character and incidence of this agent's toxicity. Only one case of renal toxicity occurred. Six cases of neurotoxicity occurred, which were characterized by perioral paresthesia, ataxia, or both. The rate of intolerable renal adverse effects secondary to colistin therapy was appreciably lower among these patients than that reported previously for other patients. It appears that intravenous colistin can be considered for cystic fibrosis patients with strains of P. aeruginosa that are resistant to more commonly used antibiotics.

Adolescent↗
PubMed2006

Clinical and microbiological efficacy of colistin therapy in combination with rifampin and imipenem in multidrug-resistant Pseudomonas aeruginosa diabetic foot infection with osteomyelitis.

The evaluation of the safety and effectiveness of colistin in association with rifampin and imipenem in 1 diabetic patient with severe diabetic foot infection (DFI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa, complicated by osteomyelitis, is presented in this "Case Report". The patient received colistin after other ineffective antimicrobial treatment when an MDR P aeruginosa strain was isolated by cultural examination, together with a multidisciplinary care approach including surgical debridement and adequate offloading. The efficacy of combination colistin plus rifampin plus imipenem was observed with a checkerboard method and bactericidal activity of the serum. The patient received colistin combination therapy for 6 weeks with cure of the infection and without renal toxicity. These data suggest that colistin, in combination with rifampin and imipenem, is safe and effective, in promoting healing in DFI due to MDR P aeruginosa and suggest the need for controlled clinical studies.

Aged↗
PubMed2005

Intrathecal colistin for treatment of highly resistant Pseudomonas ventriculitis. Case report and review of the literature.

Nosocomial infections with organisms resistant to multiple antibiotic agents represent an evolving challenge in the intensive care setting, particularly in patients requiring surgical diversion of cerebrospinal fluid. The authors present the case of a 51-year-old woman who endured protracted hospitalization and required multiple surgeries including placement of a ventriculoperitoneal shunt. The shunt subsequently became colonized with Pseudomonas aeruginosa, which demonstrated intermediate sensitivity to amikacin and full resistance to all other antibiotics tested 'After failing to respond to intravenous imipenem as well as intravenous and intrathecal amikacin, the patient was successfully treated with intravenous and intrathecal colistin. Colistin is a polymyxin-type antibiotic, rarely used outside of topical application because of reported nephrotoxicity associated with parenteral administration. With activity limited to Gram-negative organisms, colistin is bactericidal by directly disrupting the structure of cell membranes. Authors of a few case reports in the literature have described successful treatment of various ventriculitis with the intrathecal administration of colistin. With bacterial resistances outpacing the pharmaceutical industry's ability to develop novel antibiotics, colistin represents an important alternative in situations involving multidrug-resistant organisms.

Anti-Bacterial Agents↗
PubMed2006

Antimicrobial properties of erythromycin and colistin impregnated bone cement. An in vitro analysis.

Deep surgical site infection is a devastating consequence of total joint arthroplasty. The use of antibiotic impregnated bone cement is a well-accepted adjunct for treatment of established infection and prevention of deep orthopaedic infection. It allows local delivery of the antibiotic at the cement-bone interface and sustained release of antibiotic provides adequate antibiotic coverage after the wound closure. Preclinical testing, randomised and clinical trials indicate that the use of antibiotic-impregnated bone cement is a potentially effective strategy in reducing the risk of deep surgical site infection following total joint arthroplasty. The purpose of this study was to assess antibacterial activity of erythromycin and colistin impregnated bone cement against strains of organisms' representative of orthopaedic infections including Gram-positive and Gram-negative aerobic organisms: Staphylococcus aureus, coagulase-negative Staphylococci, Enterococcus sp., Proteus sp., Klebsiella sp., Pseudomonas sp., and Escherichia coli. Pre-blended Simplex P bone cement with the addition of erythromycin and colistin (Howemedica Inc) was mixed thoroughly with 20ml liquid under sterile conditions to produce uniform cylindrical discs with a diameter of 14mm and thickness of 2mm. 24-48 hour agar cultures of Staphylococcus aureus, coagulase-negative Staphylococci, Enterococcus sp.,Proteus sp., Klebsiella sp.,Pseudomonas sp., and Escherichia coli were used for the agar diffusion tests. The agar plates were streaked for confluent growth followed by application of erythromycin and colistin impregnated bone cement disc to each agar plate. The plates were incubated at 30 degrees C and examined at 24, 48, 72 hours, and four and five days after the preparation of the impregnated cement. The susceptibility of Staphylococcus aureus to the control discs was most clearly demonstrated showing a distinct zone of inhibition. The zone observed around coagulase-negative Staphylococci, Klebsiella sp., Pseudomonas sp., and Escherichia coli were also significant. However, there was no zone of inhibition or signs of antibacterial activity at the cemented surface were detected around discs with Enterococcus sp. and Proteus sp. The results showed that Simplex P bone cement with the addition of erythromycin and colistin was effective against most of the broad spectrum organisms encountered during total joint arthroplasty. The activity of Simplex P bone cement impregnated with erythromycin and colistin is mainly during the first 72 hours.

Anti-Bacterial Agents↗
PubMed1981

[The child's intestinal ecosystem: effect of colistin (author's transl)].

A differential quantitative study of the fecal flora was used to appreciated the intestinal bacterial flora of 41 hospitalized children, with no infection and receiving no antibiotic treatment. Thus, it was possible to establish the bacterial normal profile of intestinal of hospitalized child. Because of the stability of the fecal flora in those controls, it was possible to study the effect of colistin on the intestinal ecosystem, in 21 children. Colistin per os, with intestinal nutrition and colistin IM in combination with gentamicin IM did not have any quantitative or qualitative effect on fecal flora. Colistin per os, with exclusive parenteral nutrition caused by disappearance of sensitive strains and their replacement by resistant organisms; this was followed by secondary septicaemia. This fact being a very high infectious risk, it leads us to abstain from administering colistin per os, when the intestine does not receive any food.

Administration, Oral↗
PubMed2002

Transmission of colistin-resistant Pseudomonas aeruginosa between patients attending a pediatric cystic fibrosis center.

We report on an outbreak of colistin-resistant Pseudomonas aeruginosa (CRPA) that occurred in a United Kingdom pediatric cystic fibrosis (CF) unit and involved six children over a period of 5 years. All CRPA-positive children had received aerosolized colistin therapy before first isolation of resistant organisms (mean duration, 3.1 years). Four of the 6 had also received courses of intravenous colistin in the year before the first isolation of CRPA. No impact of CRPA acquisition on respiratory function, clinical condition, or radiological parameters could be demonstrated. Four of the 6 children carried isolates of CRPA indistinguishable on genotyping. Two of these 4 children were sisters. The other 2 were on the same ward together at time of first isolation, and subsequently shared overlapping admissions with one of the sisters. While there is no conclusive evidence for the route of transmission, the frequency of overlapping in-patient admissions between 3 of these patients is suggestive of patient-to-patient transfer in the nosocomial setting.CF clinicians should be aware that colistin resistance can occur in P. aeruginosa, and some of these strains are capable of spread within CF units.

Anti-Bacterial Agents↗
PubMed1996

Depletion of the residues of colistin and amoxicillin in turkeys following simultaneous subcutaneous administration.

The tissue distribution and depletion of colistin and amoxicillin were studied in 84 turkeys dosed subcutaneously on 4 consecutive days with a formulation containing the two drugs at 0.2 ml/kg per day, corresponding to 50 000 IU of colistin sulphate/kg and 20 mg of amoxicillin trihydrate/kg. All the turkeys were killed 1-30 days after the final dose and samples of muscle, liver, kidney and cutaneous-subcutaneous tissues and of the injection site were taken for analysis for colistin and amoxicillin residues. The colistin concentrations in the liver (117.5 +/- 26.0 ng/g) and cutaneous-subcutaneous tissue (100.0 +/- 35.6 ng/g) were higher than those in kidney (92.0 +/- 34.4 ng/g) or muscle (67.5 +/- 16.9 ng/g) 1 day after the final dose. The concentration of this drug then increased for 9-14 days, followed by a slow decrease. The antibiotic was still present at low concentrations in the kidneys of all the treated birds and in the livers of two turkeys 30 days after the end of treatment. Amoxicillin concentrations were greatest in muscle (389.2 +/- 195.0 ng/g) and at the injection sites (440.3 +/- 213.9 ng/g) 1 day after treatment ceased, with a subsequent rapid decline. This drug was undetectable in the livers and kidneys by 10 days after dosing ceased.

Amoxicillin↗
PubMed2006

Dry powder inhalation of colistin in cystic fibrosis patients: a single dose pilot study.

BACKGROUND: Dry powder inhalation (DPI) may be an alternative to nebulisation of drugs in the treatment of chest infections in cystic fibrosis (CF) patients. In a pilot study the feasibility of a colistin dry powder inhaler (prototype Twincer) by a single dose in CF-patients was assessed and compared to nebulised colistin. METHODS: Ten CF-patients, chronically infected with P. aeruginosa, participated in a randomised cross over study. On two visits to the outpatient clinic, patients inhaled colistin sulphomethate as 25 mg dry powder (Twincer) or as 158 mg nebulised solution (Ventstream nebuliser, PortaNeb compressor). Pulmonary function tests were performed before, 5 and 30 min after inhalation. Serum samples were drawn prior to each dose and at 15, 45 min, 1.5; 2.5; 3.5 and 5.5 h after inhalation. RESULTS: The DPI was well tolerated by the patients: no significant reduction in FEV1 was observed. Relative bioavailability of DPI to nebulisation was approx. 140% based on actual dose and approx. 270% based on drug dose label claim. CONCLUSIONS: The colistin DPI (Twincer inhaler) is well tolerated and appreciated by CF-patients. Optimisation with respect to particle size and internal resistance of the inhaler is necessary to attain equivalent pulmonary deposition to liquid nebulisation.

Administration, Inhalation↗
PubMedDate not supplied

Antimycobacterial spectrum of colistin (polymixin E).

Minimal inhibitory concentrations and minimal bactericidal concentrations of colistin (polymyxin E) were determined for the type strains of fifteen mycobacterial species. Colistin was found to be active against pathogenic species Mycobacterium xenopi, M. intracellulare, M. tuberculosis, M. fortuitum and also against the rapidly growing, non-pathogenic species M. phlei and M. smegmatis. The discriminatory potential of susceptibility to colistin as a test was investigated on 25 strains of the M. fortuitum/M. chelonei complex, and also on 11 strains of the M. avium/M. intracellulare complex. The experimental data indicated the potential of colistin susceptibility testing for discriminating M. fortuitum from M. chelonei.

Colistin↗
PubMed2001

Oral ciprofloxacin plus colistin: prophylaxis against bacterial infection in neutropenic patients. A strategy for the prevention of emergence of antimicrobial resistance.

Following a 2-year study, the combination of oral ciprofloxacin and colistin has been used continuously for 10 years without the emergence of resistance. During a 2-year period (1987-1989), we compared ciprofloxacin + colistin (CIP + COL) with neomycin + colistin (NEO + COL) in a randomized trial--combinations chosen because of the potential for prophylaxis of Gram-negative infection by ciprofloxacin, with colistin given to reduce the risk of emergence of resistance. Sixty-four patients with similar demographics in each arm were evaluable for efficacy analysis. Patients on CIP + COL had a significantly lower proportion of neutropenic days with fever (P < 0.001) and neutropenic days on intravenous antibiotics (P < 0.001) than patients on NEO + COL. A total of 54 (15 bacteriologically documented) pyrexial episodes occurred in patients on CIP + COL and 77 (41 bacteriologically documented) in patients on NEO + COL. Only two Gram-negative bacterial infections occurred in the CIP + COL arm compared with 16 in the NEO + COL arm. No Staphylococcus aureus infections occurred in the CIP + COL group compared with 10 in the other patients. Two CIP-resistant Gram-negative bacilli were isolated from patients on CIP + COL compared with 13 NEO-resistant Gram-negative bacilli from patients on NEO + COL. Following a subsequent decade of unchanged use of this prophylactic strategy in neutropenic patients, a 2-year follow-up study between 1 January 1998 and 31 December 1999 showed 66 significant infections during 700 [corrected] neutropenic episodes. Thirty-five of the 111 (31%) isolates were ciprofloxacin-resistant, involving 5% of the neutropenic episodes [corrected].

Adolescent↗
PubMed2003

Use of parenteral colistin for the treatment of serious infection due to antimicrobial-resistant Pseudomonas aeruginosa.

Serious infection due to strains of Pseudomonas aeruginosa that exhibit resistance to all common antipseudomonal antimicrobials increasingly is a serious problem. Colistin was used as salvage therapy for 23 critically ill patients with multidrug-resistant P. aeruginosa infection. Twenty-two patients who had septic shock (n=14) and/or renal failure (n=21) received mechanical ventilatory support at baseline. The most common types of infection were pneumonia (n=18) and intra-abdominal infection (n=5). Colistin was administered for a median of 17 days (range, 7-36 days). Seven patients died during therapy, at a median of 17 days (range, 4-26 days) after initiation of treatment. A favorable clinical response was observed in 14 patients (61%); only 3 patients experienced relapse. Bacteremia was the only significant factor associated with treatment failure (P=.02). One patient manifested diffuse weakness that resolved after temporary cessation of colistin therapy. Colistin provides an important salvage therapeutic option for patients with otherwise untreatable serious P. aeruginosa infection.

Adult↗
PubMed2006

Parenteral and inhaled colistin for treatment of ventilator-associated pneumonia.

The spectrum of available therapeutic options has become drastically narrowed in recent years, particularly for nosocomial multidrug-resistant gram-negative pathogens. This therapeutic void has created a resurgence of interest in colistin. In 5 published series since 1999, clinical response rates for pneumonia due to Pseudomonas aeruginosa or Acinetobacter baumannii treated with intravenous colistin have ranged from 25% to 62%, despite high severity of illness at baseline. De novo nephrotoxicity was observed in 8%-36% of patients, despite close attention to both appropriate dosing and duration of treatment. Neurotoxicity, which was commonly described in the old colistin era, has been exceedingly rare in recent experience. Aerosolized therapy as an adjunct to systemic treatment appears promising, but the current published data are much too limited to allow determination of the incremental benefit of the addition of aerosolized treatment to systemic treatment. Colistin is a reasonably safe last-line therapeutic alternative for pneumonia due to multi- or panresistant P. aeruginosa or A. baumannii.

Acinetobacter↗
PubMed2001

The clinical use of colistin in patients with cystic fibrosis.

Colistin is a cationic polypeptide antibiotic from the polymyxin family that was first introduced in 1962 but abandoned in the early 1970s because of initial reports of severe toxicities. However, a recent increase in the prevalence of multidrug resistant (MDR) Pseudomonas aeruginosa and the lack of novel agents in development calls for a need to re-examine the role of colistin therapy in patients with cystic fibrosis. Current data supports the use of intravenous colistimethate for the treatment of acute pulmonary exacerbations involving MDR P. aeruginosa and inhaled therapy for initial colonization. The frequency of nephrotoxicity and severity of neurotoxicity seem to be substantially less than previously believed. In addition, recent pharmacokinetic and pharmacodynamic data suggests new intravenous dosing regimens may enhance efficacy while minimizing toxicities; such regimens deserve further evaluation. Pre- and post-treatment spirometry is recommended at initiation of inhaled colistin therapy to identify sensitized individuals. Judicious use of colistin where the benefits have been clearly documented will retain this as a useful agent in the management of P. aeruginosa infections in patients with cystic fibrosis.

Anti-Bacterial Agents↗
PubMed2004

Colistin efficacy in an experimental model of Acinetobacter baumannii endocarditis.

The in-vivo activity of colistin was evaluated in an experimental rabbit model of Acinetobacter baumannii endocarditis with a strain susceptible to colistin and intermediate to imipenem. Compared to a control group, colistin was effective (p < 0.05) in bacterial clearance from blood and in the sterilisation of blood cultures, but was not effective in clearing A. baumannii from vegetations. Thus, although colistin may be effective in treating bacteraemia caused by susceptible strains of A. baumannii, it may not be a suitable treatment for endocarditis, perhaps because of poor penetration into vegetations and a low C(max)/MIC ratio in tissue.

Acinetobacter Infections↗
PubMed2005

Colistin treatment in patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria: the renaissance of an old antibiotic.

A retrospective case series study was performed in a 30-bed general intensive care unit (ICU) of a tertiary care hospital to assess the effectiveness and safety of colistin in 43 critically ill patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria. Various ICU-acquired infections, mainly pneumonia and bacteraemia caused by multiresistant strains of Pseudomonas aeruginosa and/or Acinetobacter baumannii, were treated with colistin. Good clinical response (cure or improvement) was noted in 74.4% of patients. Deterioration of renal function occurred in 18.6% of patients during colistin therapy. Nephrotoxicity was elevated significantly in those patients with a history of renal failure (62.5%). All-cause mortality amounted to 27.9%. In this group of critically ill patients, an age of >50 years (OR, 5.4; 95% CI 1.3-24.9) and acute renal failure (OR, 8.2; 95% CI 2.9-23.8) were independent predictors of mortality. Colistin should be considered as a treatment option in critically ill patients with infection caused by multiresistant Gram-negative bacilli.

Adult↗
PubMed1985

Antibacterial action of colistin (polymyxin E) against Mycobacterium aurum.

Mycobacterium aurum was susceptible to the antibiotic colistin (polymyxin E),which had an MIC of 5 micrograms/ml and an apparent bactericidal effect at concentrations above 50 micrograms/ml. Treatment of actively growing cells with sublethal concentrations of colistin (15 micrograms/ml) resulted in synchronized cell division once the antibiotic was removed. Under conditions of synchronized cell growth, one cycle of DNA replication lasted 120 min and one cycle of cell division lasted about 180 min. Although the antibiotic treatment during synchronization experiments did not produce apparent changes in the bacterial envelope, it was accompanied by the accumulation of a polysaccharide-like substance in the bacterial cytoplasm which gradually decreased after the removal of antibiotic and by an increase in the number of mesosomes at 3 h after antibiotic removal. This step was closely linked to the doubling time of bacteria. Lethal concentrations of colistin of 50 and 100 micrograms/ml, which caused about 90 and 99% cell death, respectively, produced significant cytoplasmic membrane injuries, patchy appearance of the cell wall outer polysaccharide layer, and little cell lysis. These data indicate that the cytoplasmic membrane is a site of action of colistin and raise a question as to whether an outer bilayer exists in mycobacteria, at least functionally.

Cell Division↗