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PubMed2006

Pharmacokinetics of inhaled colistin in patients with cystic fibrosis.

OBJECTIVES: Inhaled colistin is commonly used in patients with cystic fibrosis (CF), but only limited data are available to define its pharmacokinetic profile. PATIENTS AND METHODS: We performed a multicentre study in 30 CF patients to assess sputum, serum and urine concentrations after a single dose of 2 million units of colistin administered by inhalation. In a subgroup of patients we also compared the efficacy of two different nebulizers for administration of inhaled colistin. RESULTS: Serum concentrations of colistin reached their maximum 1.5 h after inhalation and decreased thereafter. Serum concentrations were well below those previously reported for systemic application in all patients. A mean 4.3+/-1.3% of the inhaled dose was detected in urine. Elimination characteristics did not differ significantly from those previously reported for systemic application. A positive correlation was found between forced expiratory volume in 1 s (FEV1) in per cent predicted and both AUC and maximal colistin concentrations in serum (Cmax). Maximum sputum concentrations were at least 10 times higher than the MIC breakpoint for Pseudomonas aeruginosa proposed by the British Society for Antimicrobial Chemotherapy. Although sputum drug concentrations decreased after a peak at 1 h, the mean colistin concentrations were still above 4 mg/L after 12 h. No differences were seen in polymyxin E sputum concentrations, for CF patients between the two nebulizer systems. CONCLUSIONS: The low systemic and high local concentrations of colistin support the use of inhaled colistin in CF patients infected with P. aeruginosa.

Administration, Inhalation↗

PubMed2003

Synergistic activity of colistin and ceftazidime against multiantibiotic-resistant Pseudomonas aeruginosa in an in vitro pharmacodynamic model.

Despite the marketing of a series of new antibiotics for antibiotic-resistant gram-positive bacteria, no new agents for multiple-antibiotic-resistant gram-negative infections will be available for quite some time. Clinicians will need to find more effective ways to utilize available agents. Colistin is an older but novel antibiotic that fell into disfavor with clinicians some time ago yet still retains a very favorable antibacterial spectrum, especially for Pseudomonas and Acinetobacter spp. Time-kill curves for two strains of multiantibiotic-resistant Pseudomonas aeruginosa were generated after exposure to colistin alone or in combination with ceftazidime or ciprofloxacin in an in vitro pharmacodynamic model. MICs of colistin, ceftazidime, ciprofloxacin, piperacillin-tazobactam, imipenem, and tobramycin were 0.125, > or =32, >4, >128/4, 16, and >16 mg/liter, respectively. Colistin showed rapid, apparently concentration-dependent bactericidal activity at concentrations between 3 and 200 mg/liter. We were unable to detect increased colistin activity at concentrations above 18 mg/liter due to extremely rapid killing. The combination of colistin and ceftazidime was synergistic (defined as at least a 2-log(10) drop in CFU per milliliter from the count obtained with the more active agent) at 24 h. Adding ciprofloxacin to colistin did not enhance antibiotic activity. These data suggest that the antibacterial effect of colistin combined with ceftazidime can be maximized at a peak concentration of < or =18 mg/liter.

Anti-Bacterial Agents↗

PubMed2005

Combination therapy with intravenous colistin for management of infections due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis.

Colistin, an antibiotic almost abandoned for intravenous administration for many years due to its reported toxicity, has been recently reintroduced in clinical practice due to the emergence of multidrug-resistant gram-negative bacteria and the lack of development of new antibiotics to combat them. To assess the safety and effectiveness of intravenous colistin, in combination with other antimicrobial agents, in the treatment of serious infections in patients without cystic fibrosis, a retrospective cohort study in a 450-bed tertiary-care hospital in Athens, Greece, was performed. Patients who were hospitalized from 1 October 2000 to 31 January 2004 and received intravenous colistin for more than 72 h were further analyzed. The primary outcome measure was the in-hospital mortality; secondary end points were the clinical outcome of the infections and the occurrence of colistin toxicity. Fifty patients received intravenous colistin with a median (mean) daily dose of 3 (4.5) million IU for 16.5 (21.3) days for the management of 54 episodes of infections due to multidrug-resistant gram-negative bacteria. The predominant infections were pneumonia (33.3%), bacteremia (27.8%), urinary tract infection (11.1%), and intra-abdominal infection (11.1%). The responsible pathogens were Acinetobacter baumannii (51.9%), Pseudomonas aeruginosa (42.6%), and Klebsiella pneumoniae (3.7%) strains (no pathogen was isolated from one case). In-hospital mortality was 24% (12/50 patients). Clinical response (cure or improvement) of the infection was observed in 66.7% of episodes (36/54). In the studied group, serum creatinine levels were decreased, at the end of colistin treatment, by an average of 0.2 +/- 1.3 mg/dl compared to baseline levels. Deterioration of renal function during colistin therapy was observed in 4/50 patients (8%). Coadministration of other antimicrobial agents with spectrum against gram-negative microorganisms and the absence of a control group constitute the major limitations of this study. The use of intravenous colistin for the treatment of infections due to multidrug-resistant gram-negative bacteria appears to be safe and effective.

Adult↗

PubMed2003

Colistin interactions with the mammalian urothelium.

Here we describe the effect of colistin on the barrier function of the mammalian urinary bladder epithelium. Addition of colistin to the mucosal solution of the rabbit urinary bladder epithelium (urothelium) resulted in an increase in the transepithelial conductance. The magnitude of the increase in transepithelial conductance was dependent on the membrane voltage, concentration of colistin, and presence of divalent cations in the bath solution. The initial site of action of colistin was at the apical membrane. Colistin increased the membrane conductance only when the apical membrane potential was cell interior negative. The more negative the membrane potential, the larger the conductance increase. The concentration dependence of the conductance increase saturated, suggesting a membrane binding site. Divalent cations decreased the magnitude of the conductance increase. This divalent cation action occurred at two sites: one in competition with colistin for a membrane binding site, and the other by rapidly blocking the induced conductance. At short exposure times, the increase in conductance was reversed by either removing colistin from the bath or changing the voltage so that the apical membrane was cell interior positive. At long exposure times, the increase was only partially reversible by voltage or removal from the bath. This finding suggests that at long exposure times, there is a toxic effect of colistin on the urothelium.

Animals↗

PubMed1997

Nebulization and anti-Pseudomonas aeruginosa activity of colistin.

Colistin aerosols are frequently administered to patients with cystic fibrosis. However, questions arise concerning the effect of both jet and ultrasonic nebulizers on the properties of the drug. The aim of this study was to characterize the anti-Pseudomonas aeruginosa (PA) activity of colistin after jet (Pari LL) and ultrasonic (DP100) nebulization. A bench study was performed by capturing the aerosols, determining the drug mass, and assessing its anti-PA activity. Because the inhaled mass of colistin had to be entirely recovered for the bacteriological study, it was assessed by isotopic methods, mixing the drug with a 99mTc-labelled tracer and demonstrating that 99mTc activity accurately predicted the mass of colistin. Colistin was extracted from the filters and its antibiotic activity was determined using the method employed for the study of the bacteriostatic and bactericidal power of serum on the ATCC 27853 PA strain. The postnebulization minimum inhibitory concentrations (MIC) were 1.9 micrograms.mL-1 with DP100 and 0.5 microgram.mL-1 with Pari LL. These values were less than two dilutions different from the 1 microgram.mL-1 MIC of non-nebulized colistin. We conclude that neither jet nebulization nor ultrasonic nebulization alter the antibiotic properties of colistin and that both systems can be used to nebulize colistin.

Administration, Inhalation↗

PubMed2005

Use of colistin in the treatment of multiple-drug-resistant gram-negative infections.

PURPOSE: The use of colistin for the treatment of infections caused by multiple-drug-resistant (MDR) gram-negative microorganisms was studied. METHODS: The efficacy of colistin for treating infections caused by MDR gram-negative microorganisms and the development of renal toxicity were studied in hospitalized adult patients in Spain. Patients treated between January 2001 and October 2001 were included. RESULTS: Over the study period, 71 courses of inhaled colistin, 12 courses of i.v. or intramuscular (i.m.) colistin, and 2 courses of intrathecal colistin were administered to 80 patients. All were infected by MDR organisms: 69 (86%) by Acinetobacter baumannii and 11 (14%) by Pseudomonas aeruginosa. In 41 patients (51%), the episodes were caused by A. baumannii strains susceptible exclusively to colistin. The causative organisms were cleared in 92% of the patients from whom posttreatment repeat specimens were obtained. The in-hospital mortality rate was 18% (14 patients). There were no significant changes in mean serum urea or creatinine concentrations in patients receiving i.v. or i.m. therapy. CONCLUSION: Colistin was used in 80 patients infected with A. baumannii or P. aeruginosa and appeared to be efficacious and safe.

Acinetobacter Infections↗

PubMed2006

Comparison of three standardized disc susceptibility testing methods for colistin.

OBJECTIVES: With increasing antibiotic resistance in Gram-negative bacteria, the use of the polymyxins has increased in recent years. Antibiotic disc susceptibility testing remains the most widely used method in clinical laboratories, but there is very little data on the accuracy of disc testing methods for colistin. In this study, the accuracy of three standardized methods of disc susceptibility testing for colistin was compared with agar dilution. METHODS: A total of 228 clinical isolates of Acinetobacter spp., Pseudomonas aeruginosa and Enterobacteriaceae were included in the study. Isolates were tested by agar dilution for susceptibility to colistin, and results were compared with those obtained by three disc susceptibility testing methods (product insert based on CLSI methodology, British BSAC and French SFM). RESULTS: Colistin displayed good activity against Acinetobacter spp., Klebsiella spp. and Escherichia coli (MIC(90) 2 mg/L) but was less active against P. aeruginosa (MIC(90) 4 mg/L) and Enterobacter spp. (MIC(90) >or= 128 mg/L). Totally, 81%, 79% and 89% of colistin-resistant isolates were falsely reported as susceptible when tested by the product insert, BSAC and SFM testing methods, respectively. There were no false-resistant results. CONCLUSIONS: Disc susceptibility testing methods are unreliable at detecting colistin resistance. Dilution methods should be the method of choice for susceptibility testing of colistin.

Acinetobacter↗

PubMed2003

Intravenous colistin in the treatment of sepsis from multiresistant Gram-negative bacilli in critically ill patients.

INTRODUCTION: The increasing prevalence of multiresistant Gram-negative strains in intensive care units (ICUs) has recently rekindled interest in colistin, a bactericidal antibiotic that was used in the 1960s for treatment of infections caused by Gram-negative bacilli. We conducted the present observational study to evaluate the efficacy of intravenous colistin in the treatment of critically ill patients with sepsis caused by Gram-negative bacilli resistant to all other antibiotics. PATIENTS AND METHOD: Critically ill patients with sepsis caused by Gram-negative bacilli resistant to all antibiotics with the exception of colistin were treated in the six-bed ICU of a trauma hospital. Diagnosis of infection was based on clinical data and isolation of bacteria, and the bacteria were tested with respect to their susceptibility to colistin. Clinical response to colistin was evaluated. RESULTS: Twenty-four patients (mean age 44.3 years, mean Acute Physiology and Chronic Health Evaluation II score 20.6) received 26 courses of colistin. Clinical response was observed for 73% of the treatments. Survival at 30 days was 57.7%. Deterioration in renal function was observed in 14.3% of 21 patients who were not already receiving renal replacement therapy, but in only one case did this deterioration have serious clinical consequences. CONCLUSION: The lack of a control group in the present study does not allow any definite conclusions to be drawn regarding the clinical effectiveness of colistin. On the other hand, this drug has an acceptable safety profile and its use should be considered in severe infections with multiresistant Gram-negative bacilli.

Acinetobacter baumannii↗

PubMed2005

Bronchial constriction and inhaled colistin in cystic fibrosis.

STUDY OBJECTIVE: Inhaled colistin is used for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients despite reports of chest tightness and bronchospasm. The main objective of the study was to assess whether bronchospasm occurred in pediatric CF patients with or without clinical evidence of airway hyperreactivity. DESIGN AND METHODS: A prospective placebo-controlled clinical trial with crossover design was devised using challenge tests with 75 mg colistin in 4 mL saline solution and a placebo solution of the same osmolarity using a breath-enhanced nebulizer for administration. Subjects were recruited as follows: high risk (HR) for bronchospasm due to a personal history of recurrent wheezing, a family history of asthma and/or atopy, or bronchial lability, as demonstrated in pulmonary function tests; or low risk (LR) without these characteristics. RESULTS: The mean FEV(1) (expressed as the mean [+/- SD] fall from baseline) of the HR group (n = 12) fell 12 +/- 9% after placebo was administered, and fell 17 +/- 10% after colistin was administered. For the LR group (n = 8), the mean FEV(1) fell 9 +/- 4% following placebo administration and 13 +/- 8% following colistin administration. There was a greater number of subjects in the HR group compared to the LR group, which had a mean fall in FEV(1) of >/= 15% (p < 0.01) after inhaling colistin. The differences between placebo and colistin therapy in the LR group were not significant. CONCLUSION: The results demonstrated that colistin can cause bronchospasm, particularly in those patients with coexisting CF and asthma.

Administration, Inhalation↗

PubMedDate not supplied

Suspected acute interstitial nephritis induced by colistin.

We describe a 35-year-old male admitted to the intensive care unit (ICU) for acute exacerbation of chronic obstructive pulmonary disease (COPD). He developed ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and was treated with imipenem and colistin without any renal toxicity. The patient was readmitted to the ICU for a 2nd and a 3rd exacerbation of COPD and was again treated with imipenem and colistin. In both episodes, he developed rapid worsening in renal function, which improved following colistin withdrawal. Use of the Naranjo ADR probability scale indicated a probable relationship between the renal failure and the colistin therapy. In addition, the time course of events suggested that colistin was the cause of acute interstitial nephritis in this patient. We conclude that our patient had a possible acute allergic reaction to colistin since the 1st introduction was not associated with any renal toxicity and renal failure was observed on the 1st day of the 2nd and the 3rd initiation of colistin therapy, respectively.

Acute Disease↗

PubMed2005

Safety and efficacy of colistin in Acinetobacter and Pseudomonas infections: a prospective cohort study.

OBJECTIVE: To assess renal dysfunction and outcome in patients treated exclusively with colistin vs. other antibiotics. DESIGN AND SETTING: Prospective cohort study in a mixed ICU in a university-affiliated hospital. PATIENTS: 185 patients infected with Acinetobacter baumannii and Pseudomonas aeruginosa after an ICU stay longer than 48 h: 55 in the colistin group and 130 in the noncolistin group, similar in age, APACHE II, medical status, and SOFA score. MEASUREMENTS AND RESULTS: We recorded data on epidemiology and severity of illness, site of infection, renal function before and after treatment, clinical cure, and mortality. Clinical cure was defined as simultaneous normalization of central temperature (< or = 38 degrees), leukocyte count (< or = 10,000/mm3), and PaO2/FIO2 ratio (>187). Before treatment creatinine was 0.9+/-0.2 in the colistin group and 0.9+/-0.1 in the noncolistin group; after treatment the value was 1.0+/-0.3 in both groups. The most frequent infection was ventilator-associated pneumonia: 53% vs. 66% in colistin and noncolistin groups, respectively, Acinetobacter was the cause in 65% and 60% and Pseudomonas in 35% and 53%. In the noncolistin group 81% of patients were treated with carbapenems. Inadequate empirical antimicrobial treatment was more frequent in the colistin group (100% vs. 8%), but there were no differences in the frequency of clinical cure on day 6 of treatment (15% and 17%) or in mortality (29% and 24%). CONCLUSIONS: Colistin appears to be as safe and as effective as other antimicrobials for treatment of sepsis caused by Acinetobacter and Pseudomonas in critically ill patients.

APACHE↗

PubMed2006

Colistin as a salvage therapy for nosocomial infections caused by multidrug-resistant bacteria in the ICU.

The objective of this study was to determine the efficacy of systemic colistin therapy in the treatment of nosocomial infections caused by multidrug-resistant Acinetobacter baumannii or Pseudomonas aeruginosa and to study related adverse events. We prospectively studied 78 infections caused by multidrug-resistant A. baumannii or P. aeruginosa that were treated with colistin. The sites of infection were pulmonary infection (78.2%), urinary tract infection (7.7%), primary bloodstream infection (11.5%) and meningitis (2.6%). The mean daily dose of colistin was 5.5+/-1.1 MU/day (range 2-9 MU/day) and the mean duration of colistin therapy was 9.3+/-3.8 days (range 5-21 days). A favourable clinical response to colistin occurred in 60 cases (76.9%). Renal failure occurred in only seven cases. We conclude that colistin can be a safe and effective salvage therapeutic option for nosocomial infections caused by multidrug-resistant A. baumannii or P. aeruginosa.

Acinetobacter Infections↗

PubMed2007

Colistin offers prolonged survival in experimental infection by multidrug-resistant Acinetobacter baumannii: the significance of co-administration of rifampicin.

The effect of colistin on bacterial eradication and survival was tested in experimental infection by multidrug-resistant Acinetobacter baumannii. The thigh infection model was applied in 86 neutropenic Wistar rats. Six rats were used for the induction of neutropenia and for the selection of the dose regimen of colistin; the remainder was equally divided into four groups: A, controls; B, rifampicin; C, colistin; and D, both agents. Therapy was administered 5 h after bacterial challenge; 5mg/kg of rifampicin was administered intravenously and 3mg/kg of colistin intramuscularly. Survival was recorded in 10 animals of each group. The remaining 10 rats per group were killed 4h after therapy; blood and tissue samples were sampled. Median survival of animals of groups A, B, C and D was 2.00, 2.50, 4.00 and 4.00 days, respectively (P=0.0048 between A and C and P=0.0012 between A and D. Mortality rates after 6 days of follow-up were 100, 100, 100 and 70%, respectively (P=0.018 between groups). Statistically significant decreases of bacteria were found in blood, liver, lung and spleen of group B compared with A; in lung of group C compared with A; and in blood and liver of group D compared with A. Colistin was effective in prolonging survival in an experimental thigh infection by multidrug-resistant A. baumannii in neutropenic rats. Its activity was enhanced after co-administration with rifampicin. These results mandate the application of colistin in the event of infections by multidrug-resistant pathogens and the need for its co-administration with rifampicin.

Acinetobacter Infections↗

PubMed2006

Dry powder inhalation of colistin sulphomethate in healthy volunteers: A pilot study.

BACKGROUND: Pulmonary administration of the antimicrobial drugs colistin sulphomethate and tobramycin has been shown to be effective in slowing down pulmonary deterioration in cystic fibrosis (CF) patients. Both drugs are administered by liquid nebulisation, a technique known to have disadvantages. Dry powder inhalation may be an attractive alternative. We investigated inhalation of colistin sulphomethate dry powder using a newly developed Twincer device in healthy volunteers. METHODS: Eight healthy volunteers inhaled a single dose of 25mg colistin sulphomethate dry powder each, using the Twincer inhaler. The median diameter (X(50)) of the dry powder was 1.6 microm (X(10)=0.7 microm, X(90)=3.1 microm), measured by laser diffraction technique. Pulmonary function tests were performed before, 5 and 30 min after inhalation. Serum samples were drawn at t=15 min, 45 min, 1.5h, 2.5h, 3.5h, 5.5h, 7.5h and 24h after inhalation. RESULTS: The colistin sulphomethate dry powder inhaler was well tolerated: no clinically relevant effect on FEV(1) was observed nor did the volunteers experience adverse effects. CONCLUSION: Dry powder inhalation of colistin sulphomethate using the Twincer inhaler is well tolerated by healthy volunteers. A pilot study in cystic fibrosis patients is therefore considered safe in developing a dry powder inhalation of colistin for everyday CF treatment.

Administration, Inhalation↗

PubMed2001

Interactions of colistin and rifampin on multidrug-resistant Acinetobacter baumannii.

The increased incidence of nosocomial infections by multidrug-resistant Acinetobacter spp creates demand on the application of some combinations of older antimicrobials on that species. The in vitro activities of colistin and of rifampin and of their interaction were tested on 39 nosocomial isolates of Acinetobacter baumannii. All isolates were resistant to ampicillin/sulbactam, to 3(rd) and 4(th) generation cephalosporins, to amikacin and to ciprofloxacin. MICs were determined by a microdilution technique and interactive studies between 1x or 4x MIC of colistin and rifampin were performed by the time-kill assay. Rifampin was applied at a concentration of 2 microg/mL which is equal to its mean serum level. All isolates were inhibited by colistin and only 15.2% by rifampin. Synergy between 1x MIC of colistin and rifampin was detected in 15.4% of isolates at 6 h of growth and in 51.3% of isolates at 24 h of growth. Synergy between 4x MIC of colistin and rifampin was detected in 15.4% of isolates at 6 h of growth and in 66.7% of isolates at 24 h of growth. It is concluded that colistin is highly active on multidrug-resistant Acinetobacter spp and its activity on A.baumannii is increased in the presence of rifampin, so that their administration might be proposed for nosocomial infections by these isolates.

Acinetobacter↗

PubMed2006

Cure of multiresistant Acinetobacter baumannii central nervous system infections with intraventricular or intrathecal colistin: case series and literature review.

OBJECTIVES: CNS infections due to multiresistant Acinetobacter baumannii (MRAB) are an emerging problem in neurosurgical patients. Colistin remains one of the few remaining treatment options for MRAB but has poor CNS penetration. We describe our experience with intraventricular or intrathecal colistin for this infection. METHODS: Cases known to have received intraventricular or intrathecal colistin for CNS infections due to MRAB were retrospectively reviewed regarding colistin treatment, colistin efficacy and adverse events. RESULTS: Five patients were identified. All were admissions to the neurosurgical ICU and all were cured of their CNS infections. Three cases were complicated by drug-induced aseptic meningitis or ventriculitis. CONCLUSIONS: This largest case series to date shows that direct instillation of colistin into the CNS may cause chemical meningitis or ventriculitis but it is an effective treatment option for MRAB CNS infection. Further study of dosing regimens is needed.

Acinetobacter Infections↗

PubMed1982

The pharmacokinetics and tissue levels of polymyxin B, colistin and gentamicin in calves.

Following a single intravenous injection of polymyxin B, colistin (5 mg/kg, each) and gentamicin (3 mg/kg) to calves, the decline in serum antibiotic concentration generally suggested a three-compartment (open system) pharmacokinetic model. Tissue binding is a dominant factor in the distribution and elimination kinetics of the drugs. Less than 65% of the dose of polymyxin B and colistin was recovered in the urine during 48 h after treatment. Concentrations of nonbound polymyxin B and colistin in the kidney, liver, lung, heart, and skeletal muscles were similar to total (free and bound) serum drug levels, but considerably higher concentrations were found, in bound form, in chloroform-ethanol extracts of these organs. At 24 h after treatment, more than 50% of the doses of polymyxin B and colistin were present bound to the tissues; the largest amount was in the skeletal muscles. Gentamicin was concentrated in the kidney, predominantly in the free form. At 48 h after treatment the amount of gentamicin in the kidney was 6.3% of the administered dose, being more than five times greater than the corresponding amounts of polymyxin B and colistin. The extent of tissue uptake of polymyxin B and colistin limits the usefulness of kinetic values, which are derived from the analysis of serum drug levels, for the purpose of designing dosage schedules. The strong affinity of the polymyxins to the muscle tissue, and gentamicin to the kidney, can result in drug residues persisting in the body for several weeks.

Animals↗

PubMed2005

Toxicity, bioavailability and pharmacokinetics of a newly formulated colistin sulfate solution.

We formulated a new colistin sulfate injectable solution and tested its effectiveness, toxicity and pharmacokinetics in vivo on mice, rabbits, and piglets. When intramuscularly injected (i.m.) into rabbits at 0.5 mL per site, the 2.5% colistin sulfate solution caused no reaction at the injection site, but the 5.0% solution caused the muscle circumference to appear erythematic. Tested LD50 in CD-1 mice were 38.72 mg/kg for i.m. and 431.95 mg/kg for oral administration, respectively. At 15.0 mg/kg/day (i.m.) for 5 days, colistin sulfate caused obvious neurotoxicity to piglets with moderate granular degenerations in the epithelial tissues from kidney and liver. These toxic responses were not seen when colistin sulfate was injected at 10.0 mg/kg/day for 5 days. Pharmacokinetic studies revealed Cmax of 3.73 +/- 0.28 and 6.40 +/- 0.18 microg/mL, Tmax of 32 +/- 1.5 and 34 +/- 1.8 min, t(1/2beta) of 256 +/- 14 and 264 +/- 29 min, and absolute bioavailability of 95.94 and 88.45% for colistin sulfate intramuscularly injected to piglets at 2.5 and 5.0 mg/kg, respectively. Serum colistin sulfate concentration followed a two-compartment open model showing first-order absorption. The high bioavailability and the long-lasting serum retention time indicated that the new solution is suitable for i.m. in piglets with a recommended dose of 2.5 mg/kg injected twice daily.

Administration, Oral↗