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Cure of multidrug-resistant Acinetobacter baumannii fixation device-related orthopedic infections in two patients with intravenous colistin.

We report our experience with two cases of fixation device-related orthopedic infections due to multidrug-resistant Acinetobacter baumannii strains. Both patients were successfully treated with intravenous administration of colistin, despite the reported poor penetration of this medication to these tissues, in the old literature. No serious colistin-associated toxicity developed and no recurrence of the infection occurred on follow up.

Acinetobacter Infections↗

Meropenem-Colistin Combination Mitigates Porin-Associated Carbapenem Resistance Development in Ertapenem-Mono-Resistant Enterobacterales.

BACKGROUND: Non-carbapenemase-producing Enterobacterales with isolated ertapenem resistance (ETP-mono-R) may represent an early stage in the evolution toward broader carbapenem resistance, but whether further resistance induction occurs and its underlying mechanisms remain poorly understood. METHODS: Resistance induction was assessed in three Escherichia coli, four Klebsiella pneumoniae, and two Enterobacter cloacae isolates through serial exposure to subinhibitory concentrations of meropenem (MEM), imipenem, ceftazidime-avibactam, or colistin (COL), with antibiotic-free passaging for reversion. Resistance induction under MEM+COL was evaluated separately. Whole-genome sequencing (WGS), targeted porin-gene Sanger sequencing, and transcriptional analysis were used to characterize resistance mechanisms across induction stages. RESULTS: Subinhibitory MEM exposure rapidly selected for carbapenem resistance through porin-associated alterations in a species-specific manner. E. coli accumulated loop-region mutations in ompC, while K. pneumoniae predominantly developed disruptive mutations in ompK36, both accompanied by marked transcriptional downregulation. In contrast, E. cloacae retained wild-type porins but showed increased MEM MICs, suggesting a non-porin-mediated mechanism. Subinhibitory exposure to COL alone rapidly induced colistin resistance but was associated with decreased carbapenem MICs. Co-exposure to MEM and COL significantly delayed resistance development and reduced MIC increases (all P < 0.05). Targeted sequencing of 26 non-carbapenemase-producing K. pneumoniae isolates resistant to all carbapenems revealed widespread disruptive ompK36 alterations, including the S337P substitution identified experimentally, consistent with a shared permeability-loss pathway. CONCLUSIONS: In ETP-mono-R Enterobacterales, subinhibitory carbapenem exposure promotes carbapenem resistance, with porin-associated mechanisms predominating in E. coli and K. pneumoniae. Co-exposure to COL attenuates this process, suggesting a potential strategy to delay the emergence of carbapenem resistance.

Enterobacterales↗

In vitro activity of the aerosolized agents colistin and tobramycin and five intravenous agents against Pseudomonas aeruginosa isolated from cystic fibrosis patients in southwestern Germany.

Three hundred and eighty-five mucoid and non-mucoid strains of Pseudomonas aeruginosa isolated from 192 sputa from 57 adult cystic fibrosis patients were studied. Susceptibility testing using an agar dilution technique was performed for ceftazidime, ciprofloxacin, fosfomycin, meropenem and piperacillin, and the aerosolized agents colistin and tobramycin. Meropenem, ceftazidime and piperacillin were the most potent agents (susceptibility 86.2%, 84.2% and 84%, respectively). Tobramycin and colistin susceptibility rates were lower, but in light of higher intrabronchial concentrations of these drugs a greater percentage of strains might still be clinically susceptible. Only 46.2% and 41.8% of isolates were susceptible to ciprofloxacin and fosfomycin, respectively.

Aerosols↗

Synthesis and characterization of the colistin peptide polymyxin E1 and related antimicrobial peptides.

Two strategies were developed to synthesize the acylated cyclic peptides know as polymyxins. Synthesis of polymyxin E1 and several analogs enabled us to evaluate the minimum inhibitory concentration of individual compounds against Gram-negative bacteria. In this study we also report the first identification of two component peptides in the complex polymyxin fermentation product colistin, a Thr2Ser isoform and an acyl group isomer. Both of these peptides, as well as a known component peptide, Leu7Ile, were similar to polymyxin E1 in potency, suggesting that conservative mutations in the colistin family are functionally inconsequential. In contrast, the acyclic analogs of all of these peptides were inactive, indicating that the characteristic lariat structure of the polymyxins is necessary for antimicrobial activity.

Anti-Bacterial Agents↗

The value of kanamycin-colistin bladder instillations in reducing bacteriuria during intermittent catheterisation of patients with acute spinal cord injury.

Two groups of patients with acute spinal cord trauma had initial bladder management by standard non-touch techniques of intermittent catheterisation. Twenty-two patients (17 males and 5 females) had kanamycin-colistin solution instilled into the bladder at the end of each catheterisation, and 25 patients (21 males and 4 females) were not given these instillations. The incidence of significant bacteriuria during intermittent catheterisation of both males and females receiving the instillations was only half the incidence of those not receiving the instillations. Also, a significantly higher proportion of males receiving the instillations did not have any episodes of significant bacteriuria compared with those not receiving the instillations, and the same trend was evident in the small number of female patients. It is recommended that patients should have kanamycin-colistin bladder instillations when they are being intermittently catheterised.

Acute Disease↗

Development of a novel assay method for colistin sulphomethate.

Increased use of colistin therapy for infections caused by Pseudomonas aeruginosa has indicated a need for a more robust microbiological assay technique. This report describes a quick and simple microbiological assay for quantifying levels of colistin sulphomethate in serum and urine samples from cystic fibrosis patients. The technique uses no specialised or costly equipment and is suitable for use in all routine diagnostic microbiology laboratories.

Biological Assay↗

The effect of ampicillin and colistin on post-Caesarean section endometritis with identification of possible risk factors.

Two hundred and seventy eight women undergoing Caesarean section were evaluated retrospectively to determine the value of prophylactic antibiotic treatment. The patients were divided into 2 groups: 180 women who received no prophylactic treatment and 98 who were treated prophylactically with ampicillin and colistin (Colymycin). Significantly lower rates of infection with prophylactic treatment were found in all groups studied (P less than 0.001) (P less than 0.05 in the group with premature rupture of membranes). Premature rupture of membranes was found to be the only risk factor significantly altering the rate of infection in the untreated group. Patients with premature rupture of membranes or with prolonged stay in the labour room prior to surgery had a significantly higher rate of infection even after the introduction of prophylactic treatment with ampicillin and colistin (P less than 0.001).

Ampicillin↗

Comparison of tobramycin, gentamicin, colistin, and carbenicillin in Pseudomonas sepsis in monkeys.

Intravenous inoculation of 3.4 x 10(10) to 7.4 x 10(10)Pseudomonas aeruginosa organisms into rhesus monkeys 4 days after intravenous or intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate resulted in fatal sepsis in eight of nine monkeys. After intramuscular administration, in two equal doses, of 5 mg of tobramycin, gentamicin, and colistin per kg per day beginning 16 hr after challenge, 4 of 11, 4 of 11, and 3 of 10 monkeys died, respectively. Administration of daily doses of 100 to 400 mg of carbenicillin per kg was followed by death in 5 of 12. Duration of illness in the surviving monkeys in each therapy group was similar. Under the conditions of this study, prior administration of vincristine sulfate resulted in a decrease in leukocytes and enhanced susceptibility to Pseudomonas infection. Using this model for studies of comparative efficacy of antibiotics, we observed comparable results after treatment with tobramycin, gentamicin, colistin, and carbenicillin.

Aminoglycosides↗

Susceptibility of 1,500 isolates of Pseudomonas aeruginosa to gentamicin, carbenicillin, colistin, and polymyxin B.

A series of 1,500 strains of Pseudomonas aeruginosa was collected from a variety of sources to provide a group of strains which would truly represent the species. All of them were pyocine typed, and a wide range of types was included among the isolates from each source. The gentamicin, carbenicillin, colistin, and polymyxin minimal inhibitory concentration of each strain was measured by the agar dilution method employing the Steers inocula replicator. Over 99% of strains were inhibited by 8 mug of gentamicin per ml, by 256 mug of carbenicillin per ml, and by 4 mug of colistin per ml. The small number of strains more resistant to each antibiotic comprised a variety of different pyocine types. Few strains were found to be susceptible to tetracycline, chloramphenicol, kanamycin, or streptomycin at the single concentration tested.

Carbenicillin↗

Use of colistin-polymyxin B-cellobiose agar for isolation of Vibrio vulnificus from the environment.

Colistin-polymyxin B-cellobiose agar was employed for the isolation of Vibrio vulnificus from shellfish. Isolates were examined phenotypically and with a gene probe and monoclonal antibody specific for V. vulnificus. Results indicated that colistin-polymyxin B-cellobiose agar is superior to both sodium dodecyl sulfate-polymyxin B-sucrose agar and thiosulfate-citrate-bile salts-sucrose agar in its ability to select and differentiate this species from background vibrios.

Agar↗

Effectiveness of acetic acid, betadine, amphyll, polymyxin B, colistin, and gentamicin against Pseudomonas aeruginosa.

The in vitro effectiveness of three germicides and three chemotherapeutic drugs against hospital-isolated strains of Pseudomonas aeruginosa was determined. Solutions of 1% acetic acid, 0.5% Amphyll, and 0.1% Betadine were bactericidal for six strains tested within 15 min at room temperature. Over a 3-year period at the Albany Medical Center Hospital, the percentages of strains of P. aeruginosa susceptible to polymyxin B, colistin, and gentamicin did not increase. During this 3-year period, polymyxin B and colistin were administered at the hospital but gentamicin was not.

Acetates↗

Cytological aspects of antimicrobial antibiosis. I. Cytological changes associated with the exposure of Escherichia coli to colistin sulfate.

Chapman, George B. (Cornell University Medical College, New York, N.Y.). Cytological aspects of antimicrobial antibiosis. I. Cytological changes associated with the exposure of Escherichia coli to colistin sulfate. J. Bacteriol. 84:169-179. 1962-Broth cultures of Escherichia coli were exposed to different concentrations of the antibiotic colistin sulfate for various lengths of time. Control (untreated) and treated cells were fixed, dehydrated, and embedded in methacrylate or Epon. Ultrathin sections were examined in an RCA EMU2-D electron microscope. Two conspicuous cytological changes were noted. First, the nuclear material disappeared from its normal sites and was no longer demonstrable. Second, the cytoplasm lost its granularity and became homogeneous. Cells which showed these changes were nonviable.

Anti-Bacterial Agents↗

Cytological aspects of antimicrobial antibiosis. II. Cytological changes associated with the exposure of Pseudomonas aeruginosa and Bacillus megaterium to colistin sulfate.

Chapman, George B. (Cornell University Medical College, New York, N.Y.). Cytological aspects of antimicrobial antibiosis. II. Cytological changes associated with the exposure of Pseudomonas aeruginosa and Bacillus megaterium to colistin sulfate. J. Bacteriol. 84:180-185. 1962-Broth cultures of Pseudomonas aeruginosa and Bacillus megaterium were exposed to the antibiotic colistin sulfate. Control (unexposed) and exposed cells were fixed, dehydrated, and embedded in methacrylate. Ultrathin sections were examined in an RCA EMU2-D electron microscope. Two conspicuous cytological changes were noted in P. aeruginosa. The nuclear material was no longer demonstrable in its normal sites, leaving an empty space, and the cytoplasm lost its granularity, becoming homogeneous. In B. megaterium, the latter change was also noted. The nuclear material, however, although no longer demonstrable, did not leave an empty space. Rather, it seemed that cytoplasmic material had engulfed and masked nuclear areas. Cells which showed these changes were nonviable.

Anti-Bacterial Agents↗

Home-use nebulizers: a potential primary source of Burkholderia cepacia and other colistin-resistant, gram-negative bacteria in patients with cystic fibrosis.

Inhalation of aerosols contaminated with gram-negative bacteria generated from home-use nebulizers used by cystic fibrosis (CF) patients may be a primary route for bacterial colonization of the lung. Burkholderia cepacia was isolated from 3 of [corrected] 35 home-use nebulizers, and Stenotrophomonas maltophilia was isolated from 4 of 35 home-use nebulizers. Sputum cultures for two patients whose nebulizers were contaminated with B. cepacia did not yield the organism. However, DNA macrorestriction analysis by pulsed-field gel electrophoresis confirmed that one of two strains of B. cepacia recovered from the nebulizer of a third patient was also present in the sputum of that patient. Although Pseudomonas aeruginosa was isolated from 34 patients, none of the nebulizers were positive for the organism. Sixty-nine percent of nebulizers were contaminated, and up to 16 different environmental colistin-resistant, gram-negative species were identified. The heaviest contamination was found beneath the chamber atomizer. A questionnaire survey showed that the majority of patients (28 of 34) were receiving nebulized colistin and/or gentamicin. Patients who followed recommended instructions for good nebulizer hygienic practice and paid particular attention to drying had minimal or no contamination of their nebulizers.

Adult↗

Reliability of the E-test method for detection of colistin resistance in clinical isolates of Acinetobacter baumannii.

We compared the E-test to the broth microdilution method for testing the susceptibility of 115 clinical isolates of Acinetobacter baumannii to colistin. Twenty-two (19.1%) strains were resistant to colistin and 93 (80.8%) strains were susceptible according to the reference broth microdilution method. A categorical agreement of 98.2% was found, with only two (1.7%) very major errors. Agreement within 1 twofold dilution between the E-test and the broth microdilution was 16.5%. Complete agreement was found for the strains for which MICs fell within the range of 0.25 to 1 microg of colistin/ml. However, there was poor concordance, particularly in extreme dilutions with higher MICs by the E-test method.

Acinetobacter Infections↗

Treatment of nosocomial pneumonia and tracheobronchitis caused by multidrug-resistant Pseudomonas aeruginosa with aerosolized colistin.

Gram-negative bacilli including multidrug-resistant (MDR) Pseudomonas aeruginosa are responsible for a significant proportion of episodes of nosocomial pneumonia. Since the development of new antibiotics with activity against gram-negative organisms has not kept pace with the increase in prevalence of MDR pathogens, there has been renewed interest in antimicrobial agents that had previously been used but had been abandoned because of toxic side effects. This report describes three patients with nosocomial pneumonia or tracheobronchitis due to multiresistant strains of P. aeruginosa for whom aerosolized colistin proved beneficial as supplemental therapy. Aerosolized colistin merits further consideration as a therapeutic intervention for patients with pulmonary infections due to MDR P. aeruginosa.

Administration, Inhalation↗

Post-neurosurgical meningitis due to multidrug-resistant Acinetobacter baumanii treated with intrathecal colistin: case report and review of the literature.

Intrathecal colistin (Polymxin E) is becoming an important option for the treatment of post-neurosurgical meningitis caused by multidrug resistant (MDR) Acinetobacter baumannii. We report a case of 28-year-old man who developed meningitis due to MDR A. baumannii associated with an external ventricular drain. The patient was cured using a 4-week course of intrathecal colistin 3.2 mg via external ventricular drain (EVD) daily without any serious side effects.

Acinetobacter Infections↗

Endocarditis due to Pseudomonas aeruginosa in a heroin addict. Successful treatment with trimethoprim-Sulfamethoxazole mixture plus colistin.

Endocarditis of the tricuspid valve due to Pseudomonas aeruginosa in a heroin addict failed to respond to therapy with gentamicin, carbenicillin, and amikacin. Clinical and bacteriologic cure was achieved with oral administration of a trimethoprim-sulfamethoxazole mixture plus parenteral therapy with colistin. In vitro synergism was demonstrated for the three drugs at concentrations achievable in the serum. Therapy for endocarditis due to Pseudomonas continues to be a major problem; however, the successful treatment of this patient warrants consideration for instituting therapy with a trimethoprim-sulfamethoxazole misture plus colistin in individuals with this infection who fail to respond to standard therapeutic regimens for severe infections with Pseudomonas.

Adult↗