colistin and Pneumonia

The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections.. The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2.. Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients).. Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Combinations; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Minocycline; Pneumonia; Polymyxin B; Polymyxins; Tigecycline; Treatment Outcome; Urinary Tract Infections

Topics: Animals; Antibodies, Bacterial; Antineoplastic Agents; Arthritis, Infectious; Bone Diseases; Burns; Carbenicillin; Carrier State; Colistin; Cross Infection; Cystic Fibrosis; Disease Models, Animal; Drug Therapy, Combination; Gentamicins; Humans; Immunologic Deficiency Syndromes; Leukemia; Lung Diseases; Pneumonia; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Therapy; Skin Diseases, Infectious; Surgical Wound Infection; Transplantation, Homologous

Topics: Antibody Formation; Cell Membrane Permeability; Chloramphenicol; Colistin; Drug Resistance, Microbial; Drug Synergism; Gentamicins; Humans; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Sex Factors; Sputum; Time Factors; Virulence

The aim of this study was to confirm the synergistic effect of colistin/rifampicin combination therapy compared with colistin monotherapy in pneumonia caused by colistin-resistant Acinetobacter baumannii (CoRAB). The utility of the Etest was also assessed.. Nine subjects with pneumonia caused by CoRAB were enrolled from 20 July 2016 to 21 June 2018. Subjects were randomised to colistin/rifampicin combination therapy or colistin monotherapy. After exclusion of one patient who dropped out, the microbiological response (MR) and clinical response (CR) on Day 14 and mortality on Day 30 were assessed. Etest was conducted using CoRAB isolated at study enrolment.. The MR rate in the colistin/rifampicin combination group (100.0%) was better than that in the colistin group (40.0%), however the difference was not statistically significant (P=0.196). The CR rate was not significantly different between the two groups. The MR (100.0%) and CR (100.0%) rates in subjects with 'partial synergy' as shown by Etest were higher than those (25.0% and 50.0%, respectively) in subjects with 'indifferent' results (i.e. no synergistic effect), however the difference was not statistically significant (P=0.143 and 0.429, respectively). Mortality occurred in two subjects with 'indifferent' results by Etest.. Colistin/rifampicin combination therapy may have potential to achieve MR in pneumonia caused by CoRAB; however, achieving CR with this treatment is doubtful. 'Partial synergy' of colistin and rifampicin, as shown by Etest, may be a good prognostic factor [ClinicalTrial.gov ID: NCT03622918].

Topics: Acinetobacter baumannii; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Rifampin; Young Adult

Colonization of the intestinal tract has been assumed to be important in the pathogenesis of ventilator-associated pneumonia (VAP), but relative impacts of oropharyngeal, gastric, or intestinal colonization have not been elucidated. Our aim was to prevent VAP by modulation of oropharyngeal colonization, without influencing gastric and intestinal colonization and without systemic prophylaxis. In a prospective, randomized, placebo-controlled, double-blind study, 87 patients received topical antimicrobial prophylaxis (gentamicin/ colistin/vancomycin 2% in Orabase, every 6 h) in the oropharynx and 139 patients, divided over two control groups, received placebo (78 patients were studied in the presence of patients receiving topical prophylaxis [control group A] and 61 patients were studied in an intensive care unit where no topical prophylaxis was used [control group B]). Baseline characteristics were comparable in all three groups. Topical prophylaxis eradicated colonization present on admission in oropharynx (75% in study group versus 0% in control group A [p < 0.00001] and 9% in control group B patients [p < 0.00001]) and in trachea (52% versus 22% in A [p = 0.03] and 7% in B [p = 0.004]). Moreover, topical prophylaxis prevented acquired oropharyngeal colonization (10% versus 59% in A [p < 0.00001] and 63% in B [p < 0.00001]). Colonization rates in stomach and intestine were not affected. Incidences of VAP were 10% in study patients, 31% in Group A, and 23% in Group B patients (p = 0.001 and p = 0.04, respectively). This was not associated with shorter durations of ventilation or ICU stay or better survival. Oropharyngeal colonization is of paramount importance in the pathogenesis of VAP, and a targeted approach to prevent colonization at this site is a very effective method of infection prevention.. cross infection, prevention and control; respiration, artificial, adverse effects; antibiotics, administration and dosage infection control methods; pneumonia, etiology, prevention and control; intubation, intratracheal, adverse effects

Topics: Administration, Topical; Adult; Aged; Anti-Bacterial Agents; Colistin; Digestive System; Double-Blind Method; Female; Gentamicins; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Oropharynx; Pneumonia; Respiration, Artificial; Survival Analysis; Treatment Outcome; Vancomycin

To determine the influence of selective oropharyngeal decontamination (SOD) on the rate of colonization and infection of the respiratory tract in intensive care patients requiring mechanical ventilation for more than 4 days. A financial assessment was also performed.. Randomized, prospective, controlled study using amphotericin B, colistin sulfate (polymyxin E), and tobramycin applied to the oropharynx and systemic cefotaxime prophylaxis.. Anesthesiology intensive care unit (ICU) of a 1500-bed hospital.. A total of 88 patients admitted as emergencies and intubated within less than 24 h were enrolled. Fifty-eight patients received SOD and 30 patients served as controls. Randomization was in the proportion of 2 : 1 study patients to controls.. Microbiological samples from the oropharynx and other infected sites were taken at the time of admission, then twice a week and after extubation.. With the use of SOD, colonization was significantly reduced. Furthermore, the infection rate decreased from 77% in the controls to 22% in the study patients. Staphylococcus aureus was the main potential pathogen causing colonization and pneumonia. Number of days in the ICU, duration of ventilation, and mortality were not significantly decreased. The total cost of antibiotics was reduced. Development of resistance was not observed.. The use of SOD significantly reduced the colonization and pneumonia and the total charge for antibiotics. The length of stay in the ICU, duration of ventilation, and mortality were similar. No resistance was observed. Staphylococcus aureus was selected by SOD in some patients and the clinical relevance needs further observation.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Microbial; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Oropharynx; Pneumonia; Respiration, Artificial; Tobramycin

Reduction of potential pathogens by selective intestinal decontamination has been proposed to improve intensive care. Despite large scientific interest in this method, little is known about its benefit in homogeneous trauma populations.. In a prospective, controlled study, we enrolled non-infected trauma patients (age over 18 years, mechanical ventilation > or = 48 hours, intensive care for more than 3 days) who primarily were admitted to our university medical center. We randomized patients to be treated with two different topical regimens (polymyxin, tobramycin, and amphotericin (PTA) or polymyxin, ciprofloxin, amphotericin (PCA)) or the carrier only (placebo), administered four times daily both to the oropharynx and to the gastrointestinal tract. All patients received intravenous ciprofloxacin (200 mg, bd) for 4 days.. Of 357 enrolled patients, 310 (age 38.0 +/- 16.5 years, Injury Severity Score 35.2 +/- 12.7) met all inclusion criteria. Selective decontamination successfully reduced intestinal bacterial colonization. However, we did not identify significant differences between groups regarding pneumonia (PTA 47.5%, PCA 39.0%, placebo 45.3%), sepsis (PTA 47.5%, PCA 37.8%, placebo 42.6%), multiple organ failure (PTA 56.3%; PCA 52.4%, placebo 58.1%), and death (PTA 11.3%, PCA 12.2%, placebo 10.8%). Total costs per patient were highest with the PTA regimen.. We found no benefit of selective decontamination in trauma patients. Apparently, bacterial overgrowth in the intestinal tract is not the sole link between trauma, sepsis, and organ failure.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Translocation; Ciprofloxacin; Colistin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Intestines; Male; Multiple Trauma; Pneumonia; Prospective Studies; Respiration, Artificial; Tobramycin

Selective decontamination of the digestive tract with topical nonabsorbable antibiotics has been reported to prevent nosocomial infections in patients receiving mechanical ventilation, and the procedure is used widely in Europe. However, it is unclear whether selective decontamination improves survival.. We conducted a randomized, double-blind multicenter study in which 445 patients receiving mechanical ventilation in 15 intensive care units were given either prophylactic nonabsorbable antibiotics (n = 220) or a placebo (n = 225). Topical antibiotics (tobramycin, colistin sulfate, and amphotericin B) or a placebo was administered through a nasogastric tube and applied to the oropharynx throughout the period of ventilation. The main end points were the mortality rate in the intensive care unit and within 60 days of randomization.. A total of 142 patients died in the intensive care unit; 75 (34 percent) in the treatment group and 67 (30 percent) in the placebo group (P = 0.37). Mortality within 60 days of randomization was similar in the two groups (P = 0.40), even after adjustment for factors that were either unbalanced or individually predictive of survival in the two groups (P = 0.70). Pneumonia developed in 59 patients (13 percent) in the intensive care unit within 30 days of enrollment in the study (33 in the placebo group and 26 in the treatment group, P = 0.42). Pneumonia acquired in the intensive care unit and due to gram-negative bacilli was less frequent (P = 0.01) in the treatment group than in the placebo group. The total charges for antibiotics were 2.2 times higher in the treatment group.. Selective decontamination of the digestive tract does not improve survival among patients receiving mechanical ventilation in the intensive care unit, although it substantially increases the cost of their care.

Topics: Administration, Topical; Amphotericin B; Anti-Bacterial Agents; Colistin; Critical Care; Cross Infection; Digestive System; Double-Blind Method; Female; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Pneumonia; Respiration, Artificial; Survival Rate; Time Factors; Tobramycin

In a prospective randomised study, the effects of two different colonisation prophylaxis techniques on colonisation and pulmonary infection were investigated in 40 critically ill patients with long-term ventilatory support (greater than or equal to 4 days). 20 patients were selectively decontaminated with 4 x 100 g polymyxin E, 4 x 80 mg tobramycin and 4 x 500 mg amphotericin B, administered through the gastric tube and with an antimicrobial sticky paste in the oropharynx (group I). 20 patients received 50 mg of polymyxin B and 80 mg of gentamicin dissolved in 10 ml of 0.9% saline at 6 h intervals into nose, oropharynx and stomach as well as 300 mg of amphotericin B in the oropharynx only (group II). All patients received cefotaxime systemically in the first 3 days. In group I gram-negative aerobic bacteria in the pharynx decreased from 35% to 0%, in group II from 40% to 10% and in the rectum from 80% to 61% (10% in the second week) in Group I and from 100% to 73% (33% in the second week) in group II. The decrease in gram-negative microorganisms was accompanied by an increase in the frequency of Staphylococcus epidermidis. In group I, two patients developed pneumonia and two patients urinary tract infections, in group II two patients suffered from pneumonia and 3 patients urinary tract infections. Both regimes are effective methods of prophylaxis for lowering colonisation with gram-negative aerobic bacteria and the frequency of pneumonia in patients requiring long-term mechanical ventilation. A possible selection of gram-positive bacteria must be appropriately monitored.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Colistin; Critical Care; Female; Gentamicins; Humans; Male; Middle Aged; Pneumonia; Polymyxin B; Prospective Studies; Respiration, Artificial; Time Factors; Tobramycin

A double blind, placebo-controlled trial was performed to test the efficacy of prevention of nosocomial infections by selective digestive decontamination. Placebo or tobramycin (80 mg) and colistin (100 mg) was given four times daily via the gastric tube. Amphotericin B (500 mg/6 h) was administered to all patients. As our ICU is divided into two separate subunits, intestinal decontamination or placebo was administered alternatively to patients of the two subunits during two 3-month periods, separated by a 2-month period without prevention. The decontamination (n = 97) and placebo groups (n = 84) were similar with respect to age, sex, severity score and diagnostic categories on admission. Intestinal decontamination alone failed to significantly reduce the number of infected patients (26% vs 34.5%, p = 0.20), but was effective on ICU-acquired infections (0.33 vs 0.60, p = 0.02) especially gram-negative infection rates (0.17 vs 0.43, p = 0.01). The onset of the first ICU-acquired infection was delayed (9 vs 13 days, p less than 0.001) and incidence of pneumonia (2 vs 13 cases, p less than 0.01) including bacterial pneumonia (0 vs 8 cases, p less than 0.01) was significantly decreased. However, mean ICU stay and mortality were not significantly modified by intestinal decontamination.

Topics: Amphotericin B; Clinical Protocols; Colistin; Cross Infection; Double-Blind Method; Female; Humans; Intensive Care Units; Intestinal Diseases; Length of Stay; Male; Middle Aged; Pneumonia; Prospective Studies; Tobramycin

Pipemidic acid (PPA) and colistin sodium methanesulfonate (CLM) may selectively suppress aerobic gram-negative bacilli. Twenty-nine patients with acute leukemia were randomized after each course of consolidation chemotherapy to receive a single agent of nystatin (NYS) (34 courses) versus a combination of NYS, PPA and CLM (36 courses). The duration of fever over 39 degrees C was longer with the three drug combination (4.6 +/- 5.1 days) than with NYS alone (1.8 +/- 1.8 days) (P less than 0.01). Four cases of pneumonia occurred and four patients including one having pneumonia died of infection with the three drug combination, while no pneumonia or death occurred with NYS alone (P = 0.06 and P = 0.06, respectively). The combination of NYS, PPA and CLM may be less effective than NYS alone for the prevention of infection in acute leukemia patients with chemotherapy-associated granulocytopenia.

Topics: Acute Disease; Adolescent; Adult; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Colistin; Drug Therapy, Combination; Gram-Negative Bacteria; Humans; Leukemia; Middle Aged; Nicotinic Acids; Nystatin; Pipemidic Acid; Pneumonia; Random Allocation

Pseudomonas aeruginosa is a Gram-negative bacillus that often causes severe infections during immunosuppression in patients with hematologic malignancies. P. aeruginosa can easily acquire drug resistance, and often develops into multidrug-resistant P. aeruginosa (MDRP). Although many antibiotics are used in combination to treat MDRP infections, colistin and amikacin are less likely to be transferred to the lungs, and inhalation therapy may be used. Herein, we report a Case of pneumonia caused by MDRP after allogeneic hematopoietic stem cell transplantation (HSCT) treated with inhaled colistin and amikacin. This 61-year-old female patient was diagnosed with myelodysplastic syndromes and underwent allogeneic HSCT from an 8/8 HLA-matched unrelated donor after reduced-intensity conditioning. On the day of the stem cell infusion, the patient's sputum culture was found to be positive for MDRP. The patient subsequently developed bacteremia, pneumonia, and lung abscess caused by MDRP, and we administered multidrug antibiotic therapy including colistin and amikacin inhalation therapy. The patient's blood cultures were subsequently turned negative, and the lung abscess disappeared. To our knowledge, this is the first case of MDRP pneumonia after HSCT in which colistin and amikacin inhalation therapy was effective.

Topics: Amikacin; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Therapy

Early pneumonia is an independent risk factor for 1-y mortality after lung transplantation (LTx). Pseudomonas aeruginosa is the most common isolate in early pneumonia and is also associated with an increased risk of chronic lung allograft dysfunction. The aim of our study was to evaluate the efficacy of secondary prophylaxis with inhaled colistin (IC) in preventing the recurrence of P aeruginosa or extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) pneumonia in the postoperative period in the intensive care unit after LTx.. We conducted a before-and-after retrospective cohort study by including all patients who underwent LTx between January 2015 and December 2020 in our center. Secondary prophylaxis with IC was instituted in January 2018 (observation period from January 2015 to December 2017, intervention period from January 2018 to December 2020).. A total of 271 lung transplants were included (125 in the observation period and 146 in the intervention period). The patients were predominately male (64.2%) with a median age of 57 y and received double LTx (67.9%) for chronic obstructive pulmonary disease/emphysema (36.2%) or interstitial lung disease (48.3%). The proportion of patients who experienced at least 1 recurrence of P aeruginosa or ESBL-PE pneumonia was significantly lower in the intervention period than in the observation period (0.7% versus 7.2%, P = 0.007).. Our study suggests a potential benefit of secondary prophylaxis with IC to prevent the recurrence of P aeruginosa or ESBL-PE pneumonia in the intensive care unit after LTx.

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Humans; Intensive Care Units; Lung Transplantation; Male; Pneumonia; Pseudomonas aeruginosa; Retrospective Studies

Novel antibiotic combinations may act synergistically to inhibit the growth of multidrug-resistant bacterial pathogens but predicting which combination will be successful is difficult, and standard antimicrobial susceptibility testing may not identify important physiological differences between planktonic free-swimming and biofilm-protected surface-attached sessile cells. Using a nominally macrolide-resistant model Klebsiella pneumoniae strain (ATCC 10031) we demonstrate the effectiveness of several macrolides in inhibiting biofilm growth in multi-well plates, and the ability of azithromycin (AZM) to improve the effectiveness of the antibacterial last-agent-of-choice for K. pneumoniae infections, colistin methanesulfonate (CMS), against biofilms. This synergistic action was also seen in biofilm tests of several K. pneumoniae hospital isolates and could also be identified in polymyxin B disc-diffusion assays on azithromycin plates. Our work highlights the complexity of antimicrobial-resistance in bacterial pathogens and the need to test antibiotics with biofilm models where potential synergies might provide new therapeutic opportunities not seen in liquid culture or colony-based assays.

Topics: Anti-Bacterial Agents; Azithromycin; Biofilms; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mesylates; Microbial Sensitivity Tests; Pneumonia; Polymyxin B

Extensively drug-resistant Acinetobacter baumannii (XDRAB) pulmonary infection is a serious respiratory system infection. Patients are often very sick and even need to be admitted to the ICU for treatment. In this case report, we presented our treatment experience of one XDRAB pulmonary infection patient. A 71-year-old male patient was admitted to our hospital complaining of "fatigue accompanied by fever for 2 days and shortness of breath for 1 day". The patient's admission diagnosis was as follows: severe pneumonia, acute respiratory distress syndrome, I type respiratory failure, septic shock, cardiac insufficiency, liver insufficiency, and hypertension. Imipenem/cilastatin sodium combined with moxifloxacin were first applied. Then, tigecycline, imipenem/cilastatin and caspofungin were used. The drug sensitivity results suggested that the XDRAB strain of this patient's sputum culture was sensitive to polymyxin only. Thus, colistin sulfate and cefoperazone/sulbactam were applied. The medication process of the patient was monitored. We found that a colistin sulfate intravenous injection combined with aerosol route combined with cefoperazone/sulbactam was effective in the treatment of XDRAB pulmonary infection, and no adverse drug reactions were observed during the treatment. The anti-infection therapy of intravenous colistin sulfate combined with nebulization and cefoperazone/sulbactam could be a good choice for the treatment of XDRAB lung infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Male; Pharmaceutical Preparations; Pneumonia

This study aimed to explore mechanism of colistin resistance amongst Klebsiella pneumoniae isolates through plasmid mediated mcr-1 gene in Pakistan. Carbapenem and Colistin resistant K. pneumoniae isolates (n  = 34) stored at - 80 °C as part of the Aga Khan University Clinical Laboratory strain bank were randomly selected and subjected to mcr-1 gene PCR. To investigate mechanisms of resistance, other than plasmid mediated mcr-1 gene, whole genome sequencing was performed on 8 clinical isolates, including 6 with colistin resistance (MIC  >  4 μg/ml) and 2 with intermediate resistance to colistin (MIC  >  2 μg/ml).. RT-PCR conducted revealed absence of mcr-1 gene in all isolates tested. Whole genome sequencing results revealed modifications in Lipid A-Ara4N pathway. Modifications in Lipid A-Ara4N pathway were detected in ArnA_ DH/FT, UgdH, ArnC and ArnT genes. Mutation in ArnA_ DH/FT gene were detected in S3, S5, S6 and S7 isolates. UgdH gene modifications were found in all isolates except S3, mutations in ArnC were present in all except S1, S2 and S8 and ArnT were detected in all except S4 and S7. In the absence of known mutations linked with colistin resistance, lipid pathway modifications may possibly explain the phenotype resistance to colistin, but this needs further exploration.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella pneumoniae; Laboratories, Clinical; Lipid A; Microbial Sensitivity Tests; Pakistan; Plasmids; Pneumonia

Acinetobacter baumannii complex are microorganisms of critical priority of resistance, being associated with higher costs and negative outcomes for hospitalized patients. Thus, the study aimed to analyse the factors associated with A. baumannii complex infection in various hospital sectors.. This is a case-control study that included patients hospitalized from January 2017 to June 2019. Demographic, microbiological and clinical variables were collected from each patient. All cases had positive culture results for A. baumannii complex resistant to more than three classes of antimicrobials. Carbapenem-resistance was examined by the disk diffusion test, while the broth microdilution method was used to determine the susceptibility to colistin.. A. baumannii complex infection was mostly present in ICU (74.2%) than in other hospital areas. The bacteria was also linked with the length of hospitalization until the results for the culture (OR = 1.13; 95% CI: 1.06 - 1.21; p < 0.001) and with pneumonia associated with mechanical ventilation (OR = 4.48; 95% CI: 1.55 - 13.00; p = 0.006). Moreover, patients exposed to infection with multidrug-resistant A. baumannii complex had higher risks of death (OR = 3.25; 95% CI: 1.06 - 9.91; p = 0.039).. This study provides evidence that A. baumannii complex infection is associated with the number of days of hospitalization up to culture positivity, pneumonia associated with the use of mechanical ventilation and death. Infections appear to be more critical in ICU when compared to other areas. Taken together, these findings could support hospital infection surveillance programs, as well as prevention measures to reduce mortality rates and other complications.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Brazil; Carbapenems; Case-Control Studies; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Hospitals; Humans; Intensive Care Units; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Risk Factors; Young Adult

To investigate clinical and microbiological response, and 30-day mortality of pneumonia involving multidrug-resistant (MDR) Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) complex treated with colistin, and identify associated factors of these outcomes.. A retrospective study of 183 adult patients with colistin treatment for at least 7 days between January 2014 and October 2017.. The mean age was 76.8 years, and mean Acute Physiology and Chronic Health Evaluation II score was 17.7. Eighteen (9.8%) and 128 (69.9%) patients had intravenous (IV) colistin alone and inhaled (IH) colistin alone, respectively. Thirty-seven patients had both IV and IH colistin, including 5 (2.7%) with concurrent, and 32 (17.5%) with non-concurrent use of IV and IH colistin. The 30-day mortality rate was 19.1% and 131 (71.6%) patients had clinical response. In the 175 patients with available data, 126 (72%) had microbiological eradication. The multivariate analyses revealed that IH colistin alone was an independent predictor for 30-day survival, clinical response, and microbiological eradication, and IV colistin alone was an independent predictor for clinical failure. Patients with IV colistin alone had a significantly higher nephrotoxicity rate than IH colistin alone (37.5% vs 6.1%, P = 0.001). Sub-group analysis of 52 patients with IV colistin for ≧ 4 days revealed that 14 (26.9%) patients had inappropriate dose, and inappropriate dose was an independent predictor for 30-day mortality.. IH colistin provided good outcomes with few side effects, and appropriate dosing of IV colistin was important to avoid excess mortality.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Administration, Inhalation; Administration, Intravenous; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Pneumonia; Treatment Outcome

Peptide antibiotics are an abundant and synthetically tractable source of molecular diversity, but they are often cationic and can be cytotoxic, nephrotoxic and/or ototoxic, which has limited their clinical development. Here we report structure-guided optimization of an amphipathic peptide, arenicin-3, originally isolated from the marine lugworm Arenicola marina. The peptide induces bacterial membrane permeability and ATP release, with serial passaging resulting in a mutation in mlaC, a phospholipid transport gene. Structure-based design led to AA139, an antibiotic with broad-spectrum in vitro activity against multidrug-resistant and extensively drug-resistant bacteria, including ESBL, carbapenem- and colistin-resistant clinical isolates. The antibiotic induces a 3-4 log reduction in bacterial burden in mouse models of peritonitis, pneumonia and urinary tract infection. Cytotoxicity and haemolysis of the progenitor peptide is ameliorated with AA139, and the 'no observable adverse effect level' (NOAEL) dose in mice is ~10-fold greater than the dose generally required for efficacy in the infection models.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Carbapenems; Cell Membrane Permeability; Colistin; Disease Models, Animal; Drug Discovery; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Helminth Proteins; Humans; Male; Mice; Microbial Sensitivity Tests; Peritonitis; Pneumonia; Urinary Tract Infections

Unfortunately, the options for treating multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections are extremely limited. Recently, fosfomycin and minocycline were newly introduced as a treatment option for MDR A. baumannii infection. Therefore, we investigated the efficacy of the combination of colistin with fosfomycin and minocycline, respectively, as therapeutic options in MDR A. baumannii pneumonia. We examined a carbapenem-resistant A. baumannii isolated from clinical specimens at Severance Hospital, Seoul, Korea. The effect of colistin with fosfomycin, and colistin with minocycline on the bacterial counts in lung tissue was investigated in a mouse model of pneumonia caused by MDR A. baumannii. In vivo, colistin with fosfomycin or minocycline significantly (p < 0.05) reduced the bacterial load in the lungs compared with the controls at 24 and 48 h. In the combination groups, the bacterial loads differed significantly (p < 0.05) from that with the more active antimicrobial alone. Moreover, the combination regimens of colistin with fosfomycin and colistin with minocycline showed bactericidal and synergistic effects compared with the more active antimicrobial alone at 24 and 48 h. This study demonstrated the synergistic effects of combination regimens of colistin with fosfomycin and minocycline, respectively, as therapeutic options in pneumonia caused by MDR A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Fosfomycin; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Minocycline; Pneumonia; Tigecycline

BACKGROUND We investigated the factors affecting antibiotic resistance in the intensive care unit (ICU)-related hospital-acquired infections caused by Klebsiella pneumoniae (KP-HAI) and the effects of antibiotics used for high-level antibiotic resistance on patient survival. MATERIAL AND METHODS This retrospective study was performed at the adult ICU of Bezmialem Vakif University Hospital. Patients who were followed up between 01 January 2012 and 31 May 2017 were evaluated. Each KP strain was categorized according to resistance patterns and analyzed. The efficiency of antibiotic therapy for highly-resistant KP-HAI was determined by patients' lifespans. RESULTS We evaluated 208 patients. With the prior use of carbapenem, antibiotics against resistant Gram-positives, and tigecycline, it was observed that the resistance rate of the infectious agents had a significant increase. As the resistance category increases, a significant decrease was seen in the survival time. We observed that if the treatment combination included trimethoprim-sulfamethoxazole, the survival time became significantly longer, and tigecycline-carbapenem-colistin and tigecycline-carbapenem combination patients showed significantly shorter survival times. CONCLUSIONS When the resistance increases, delays will occur in starting suitable and effective antibiotic treatment, with increased sepsis frequency and higher mortality rates. Trimethoprim-sulfamethoxazole can be an efficient alternative to extend survival time in trimethoprim-sulfamethoxazole-susceptible KP infections that have extensive drug resistance.

Topics: Adult; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Resistance, Microbial; Female; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Pneumonia; Retrospective Studies; Risk Factors; Survival Rate; Tigecycline; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Colistin; Cost-Benefit Analysis; Drug Resistance, Multiple, Bacterial; Humans; Pneumonia; Saudi Arabia

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Female; Glycopeptides; Mice; Mice, Inbred C3H; Microbial Sensitivity Tests; Pneumonia; Survival Rate; Teicoplanin; Vancomycin

Few therapeutic options exist for various infections caused by extensively drug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (XDR-Acb) complex isolates, including pneumonia. This study investigated the clinical efficacy between aerosolized colistimethate sodium (AS-CMS, 2 million units thrice a day) treatment alone or in combination with standard-dose tigecycline (TGC) in patients with non-bacteremic pneumonia due to XDR-Acb, and explored the factors influencing patients' 30-day mortality.A 1:1 case (n = 106; receiving TGC plus AS-CMS) control (receiving AS-CMS alone with matching scores) observational study was conducted among adult patients with non-bacteremic XDR-Acb complex pneumonia in a Taiwanese medical center from January 2014 through December 2016. The clinically relevant data were retrospectively recorded. The primary endpoint was 30-day case fatality. Secondary endpoints investigated that if the co-morbidities, XDR-A. baumannii as a pneumonic pathogen, therapy-related factors, or airway colonization with colistin-resistant Acb negatively influenced the 14-day clinical condition of enrolled patients.A higher 30-day mortality rate was noted among the group receiving combination therapy (34.0% vs 22.6%; P = .17). The ≥7-day AS-CMS therapy successfully eradicated > 90% of airway XDR-Acb isolates. Nevertheless, follow-up sputum specimens from 10 (6.4% [10/156]) patients were colonized with colistin-resistant Acb isolates. After the conditional factors were adjusted by multivariate logistic analysis, the only factor independently predicting the 30-day case-fatality was the failure of treating XDR-Acb pneumonia at 14 days (adjusted odds ratio [aOR] = 38.2; 95% confidence interval [CI] = 9.96-142.29; P < .001). Cox proportional regression analysis found that chronic obstructive pulmonary disease (COPD) (adjusted hazard ratio [aHR] = 2.08; 95% CI = 1.05-4.10; P = .035), chronic renal failure (aHR = 3.00; 95% CI = 1.52-5.90; P = .002), non-invasive ventilation use (aHR = 2.68; 95% CI = 1.37-5.25; P = .004), and lack of TGC therapy (aHR = 0.52; 95% CI = 0.27-1.00; P = .049) adversely influenced the 14-day clinical outcomes. Conversely, the emergence of colistin-resistant Acb isolates in the follow-up sputum samples was not statistically significantly associated with curing or improving XDR-Acb pneumonia.In conclusion, aggressive pulmonary hygiene care, the addition of TGC, and corticosteroid dose tapering were beneficial in improving the

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Minocycline; Pneumonia; Retrospective Studies; Survival Rate; Taiwan; Tigecycline; Treatment Outcome

Cystic fibrosis is an autosomal recessive disorder characterized by chronic progressive multisystem involvement. AH1N1 virus infections caused classic influenza symptoms in the majority of cystic fibrosis patients while others experienced severe outcomes.. We report a case of late incidental cystic fibrosis diagnosis in a young Caucasian man suffering from respiratory failure following infection due to AH1N1 influenza virus. The patient was admitted to our department with fever, cough, and dyspnea at rest unresponsive to antibiotics CONCLUSIONS: Late diagnosis of cystic fibrosis in uncommon. This report highlights the importance of early cystic fibrosis diagnosis to minimize risk of occurrence of potential life-threatening complications.

Topics: Anti-Bacterial Agents; Ceftazidime; Colistin; Cystic Fibrosis; Delayed Diagnosis; Drainage, Postural; Genetic Testing; Humans; Incidental Findings; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Meropenem; Pneumonia; Referral and Consultation; Sweat; Thienamycins; Tomography, X-Ray Computed; Young Adult

Colistimethate sodium (CMS) is frequently used in the treatment of nosocomial multidrug-resistant gram-negative infections. Nephrotoxicity is the most important side effect. The aim of this study is to evaluate the effect of colistin on nephrotoxicity and to assess prognosis in patients treated with CMS due to hospital-acquired pneumonia (HAP).. Patients treated with CMS for HAP due to multidrug-resistant Pseudomonas aeruginosa or Acinetobacter baumannii were included in this cohort study.. We evaluated 281 patients treated with two different brands of CMS whose administration dose is different: imported (n= 58, low dose/kg) and domestic (n= 223, high dose/kg). Nephrotoxicity developed in 175 patients (62.3%). The median age (73 vs. 66 years, p= 0.004) and mortality rates were higher (66.9% vs. 52.8%, p= 0.022) in patients having nephrotoxicity. The patients receiving high dose/kg had higher nephrotoxicity rate (67.7% vs. 41.4%, p< 0.001). The clinical, bacteriological response and mortality rates of the whole group were 52.0%, 61.0%, 61.6%, respectively. The clinical and bacteriological response rates were similar in the different dose groups. Multivariate analysis showed that nephrotoxicity was associated with domestic brand depending on use of high dose (OR= 3.97), advanced age (β= 0.29, p= 0.008), male gender (OR= 2.60), hypertension (OR= 2.50), red blood cells transfusion (OR= 2.54), absence of acute kidney injury (OR= 10.19), risk stage of RIFLE (OR= 11.9).. Nephrotoxicity is associated with the use of high dose colistin, age, gender, hypertension, red blood cells replacement and RIFLE stage. The mortality rate is higher in patients developing nephrotoxicity.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia; Prognosis; Renal Insufficiency

Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia.. A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria.. Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy.. The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Pneumonia; Retrospective Studies

We described 27 polyclonal colistin-resistant Enterobacteriaceae (MIC 4-16 μg/mL) infections (12 pneumonia, 12 urinary tract infection (UTI), two Bacteremia, and one skin/soft tissue infection) in which 74% harbored KPC. The isolates were polyclonal, 6 STs were identified and the colistin resistance was due to chromosome mutations. Eight patients with UTI received monotherapy, and combination therapy was given to 19 patients. Overall mortality was 37%. In vitro synergy using time-kill assay was observed in 14 of 19 (74%) isolates tested; the synergistic effect was observed for almost all isolates for the combination of three drugs: colistin, amikacin, and tigecycline. The Kaplan-Meier survival curve showed no significant difference comparing combination therapy with 2, 3, or more drugs and risk factors associated with death were dialysis and shock. These findings reinforce the fact that colistin in combination with other classes of drugs can be useful in treating infections caused by colistin-resistant CRE.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Kaplan-Meier Estimate; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia; Prospective Studies; Soft Tissue Infections; Tigecycline; Urinary Tract Infections

Minocycline-based combination therapy has been suggested to be a possible choice for the treatment of infections caused by minocycline-susceptible Acinetobacter baumannii, but its use for the treatment of infections caused by minocycline-resistant A. baumannii is not well established. In this study, we compared the efficacy of minocycline-based combination therapy (with colistin, cefoperazone-sulbactam, or meropenem) to that of colistin in combination with meropenem for the treatment of minocycline-resistant A. baumannii infection. From 2006 to 2010, 191 (17.6%) of 1,083 A. baumannii complex isolates not susceptible to minocycline from the Taiwan Surveillance of Antimicrobial Resistance program were collected. Four representative A. baumannii isolates resistant to minocycline, amikacin, ampicillin-sulbactam, ceftazidime, ciprofloxacin, cefepime, gentamicin, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam were selected on the basis of the diversity of their pulsotypes, collection years, health care setting origins, and geographic areas of origination. All four isolates had tetB and overexpressed adeABC, as revealed by quantitative reverse transcription-PCR. Among all minocycline-based regimens, only the combination with colistin produced a fractional inhibitory concentration index comparable to that achieved with meropenem combined with colistin. Minocycline (4 or 16 μg/ml) in combination with colistin (0.5 μg/ml) also synergistically killed minocycline-resistant isolates in time-kill studies. Minocycline (50 mg/kg of body weight) in combination with colistin (10 mg/kg) significantly improved the survival of mice and reduced the number of bacteria present in the lungs of mice compared to the results of monotherapy. However, minocycline (16 μg/ml)-based therapy was not effective at reducing biofilm-associated bacteria at 24 or 48 h when its effectiveness was compared to that of colistin (0.5 μg/ml) and meropenem (8 μg/ml). The clinical use of minocycline in combination with colistin for the treatment of minocycline-resistant A. baumannii may warrant further investigation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Biofilms; Cefepime; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Gentamicins; Imipenem; Meropenem; Mice; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Taiwan; Thienamycins

Immune response stimulation to prevent infection progression may be an adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC) is an immunomodulator involved in immune cell recruitment and activation. In this study, we aimed to evaluate the efficacy of LPC in combination with colistin, tigecycline, or imipenem in experimental murine models of peritoneal sepsis and pneumonia. We used Acinetobacter baumannii strain Ab9, which is susceptible to colistin, tigecycline, and imipenem, and multidrug-resistant strain Ab186, which is susceptible to colistin and resistant to tigecycline and imipenem. Pharmacokinetic and pharmacodynamic parameters for colistin, tigecycline, and imipenem and the 100% minimal lethal dose (MLD100) were determined for both strains. The therapeutic efficacies of LPC, colistin (60 mg/kg of body weight/day), tigecycline (10 mg/kg/day), and imipenem (180 mg/kg/day), alone or in combination, were assessed against Ab9 and Ab186 at the MLD100 in murine peritoneal sepsis and pneumonia models. The levels of pro- and anti-inflammatory cytokines, i.e., tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay (ELISA) for the same experimental models after inoculating mice with the MLD of both strains. LPC in combination with colistin, tigecycline, or imipenem markedly enhanced the bacterial clearance of Ab9 and Ab186 from the spleen and lungs and reduced bacteremia and mouse mortality rates (P < 0.05) compared with those for colistin, tigecycline, and imipenem monotherapies. Moreover, at 4 h post-bacterial infection, Ab9 induced higher TNF-α and lower IL-10 levels than those with Ab186 (4 μg/ml versus 3 μg/ml [P < 0.05] and 2 μg/ml versus 3.4 μg/ml [P < 0.05], respectively). LPC treatment combined with colistin, tigecycline, or imipenem modestly reduced the severity of infection by A. baumannii strains with different resistance phenotypes compared to LPC monotherapy in both experimental models.

Topics: Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Colistin; Enzyme-Linked Immunosorbent Assay; Imipenem; Interleukin-10; Lysophosphatidylcholines; Mice; Microbial Sensitivity Tests; Minocycline; Pneumonia; Sepsis; Tigecycline; Tumor Necrosis Factor-alpha

A synthetic antimicrobial peptide was identified as a possible candidate for the development of a new antibacterial drug. The peptide, SET-M33L, showed a MIC90 below 1.5 μM and 3 μM for Pseudomonas aeruginosa and Klebsiella pneumoniae, respectively. In in vivo models of P. aeruginosa infections, the peptide and its pegylated form (SET-M33L-PEG) enabled a survival percentage of 60-80% in sepsis and lung infections when injected twice i.v. at 5 mg/Kg, and completely healed skin infections when administered topically. Plasma clearance showed different kinetics for SET-M33L and SET-M33L-PEG, the latter having greater persistence two hours after injection. Bio-distribution in organs did not show significant differences in uptake of the two peptides. Unlike colistin, SET-M33L did not select resistant mutants in bacterial cultures and also proved non genotoxic and to have much lower in vivo toxicity than antimicrobial peptides already used in clinical practice. The characterizations reported here are part of a preclinical development plan that should bring the molecule to clinical trial in the next few years.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Female; Humans; Klebsiella pneumoniae; Male; Mice; Mice, Inbred BALB C; Pneumonia; Polyethylene Glycols; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Skin

To describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death.. A prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7.0 (CDC, Atlanta, GA, USA) and SPSS (Chicago, IL, USA).. One hundred and twenty-seven patients were evaluated. Pneumonia, 52 (42 %), and urinary tract infections (UTI), 51 (40.2 %), were the most frequent sites of infection. The isolates were polyclonal; the Bla. CRE infection mortality was higher among patients with pneumonia. Infections caused by colistin-resistant isolates did not increase mortality. The use of more than two drugs on combination therapy did not show a protective effect on outcome. The isolates were polyclonal, and the bla

Topics: Adult; Age Factors; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cohort Studies; Colistin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Hospital Mortality; Humans; Kidney Failure, Chronic; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Polymerase Chain Reaction; Prospective Studies; Renal Dialysis; Risk Factors; Shock, Septic; Urinary Tract Infections

Sepsis due to multidrug-resistant Gram-negative pathogens is a challenge for clinicians and microbiologists and has led to use of parenteral colistin. There is a paucity of data regarding safety and efficacy of intravenous colistin use in neonates. The objective of this retrospective analysis was to study the efficacy and safety of intravenous colistin in the treatment of neonatal sepsis.. An audit of the data from neonates, admitted to a neonatal intensive care unit of a tertiary care hospital during January 2012 to December 2012, and who received intravenous colistin was carried out.. Sixty two neonates received intravenous colistin (52 preterm and 10 term) for the treatment of pneumonia, bloodstream infections and meningitis. The isolated pathogens in decreasing order of frequency were Acinetobacter baumannii, Klebsiella pneumonia and Pseudomonas aeruginosa. Of the total 62 neonates, 41 (66.12%) survived and 21 (33.87%) died. Significantly higher mortality was observed in neonates with lower body weights (P < 0.05). A significant association of mortality was found in those with sepsis due to Klebsiella species. Only one of seven with this infection survived as against 15 of the 23 who grew other organisms [P = 0.03; crude odds ratio = 11.25 (1.2, 110.5)]. None of the neonates developed neurotoxicity or nephrotoxicity.. This retrospective study in neonates with sepsis showed that intravenous colistin was safe and effective in the treatment of neonatal sepsis. Further, well-controlled, prospective clinical trials need to be done to corroborate these findings.

Topics: Acinetobacter baumannii; Administration, Intravenous; Colistin; Female; Humans; Infant, Newborn; Klebsiella pneumoniae; Male; Meningitis; Neonatal Sepsis; Pneumonia; Pseudomonas aeruginosa; Tertiary Care Centers

Colistin is used for the treatment of pneumonia associated with multidrug- resistant Acinetobacter baumannii and Pseudomonas aeruginosa. However, the best route of administration and dosage is not known. We report our experience with aerosolized colistin in twelve patients with pneumonia caused by colistin-only-susceptible (COS) A. baumannii.. We retrospectively reviewed patients' medical records who were treated with aerosolized colistin for the treatment of pneumonia.. Ten patients were treated only with aerosolized colistin inhalation and two patients received a 3-day course intravenous colistin, and then switched to colistin inhalation therapy. The median duration of aerosolized colistin therapy was 17 days (5-31 days). Four patients were treated only with aerosolized colistin, whereas 4 patients received concomitant glycopeptides, and 4 received concomitant levofloxacin or cefoperazone/sulbactam. At the end of the therapy, the clinical response rate and bacteriological clearance rate was 83% and 50%, respectively. Colistin-resistant strains were isolated from 3 patients after aerosolized colistin therapy; however, all of them showed favorable clinical response. The median interval between inhalation therapy and resistance was 7 days (range 5-19 days). Acute kidney injury developed in 3 patients. Two patients experienced Clostridium difficile associated diarrhea. One patient developed fever and skin rash after aerosolized colistin therapy. No patient developed neurotoxicity or bronchospasm.. Colistin inhalation therapy is deemed tolerable and safe, and could be beneficial as an adjuctive therapy for the management of pneumonia due to COS A. baumannii. However, the potential development of colistin resistance cannot be overlooked.

Topics: Acinetobacter baumannii; Administration, Inhalation; Aged; Anti-Bacterial Agents; Colistin; Female; Humans; Male; Middle Aged; Pneumonia; Retrospective Studies

Colistin and tigecycline have both been shown good in vitro activity among multi-drug resistant Acinetobacter baumannii (MDRAB). A comparative study of colistin versus tigecycline for MDRAB pneumonia is lacking.. The study enrolled adults with MDRAB pneumonia admitted to intensive care units at a referral medical center during 2009-2010. Since there were no standardized minimum inhibitory concentration (MIC) interpretation criteria of tigecycline against A. baumannii, MIC of tigecycline was not routinely tested at our hospital. During the study periods, MIC of colistin was not routinely tested also. We consider both colistin and tigecycline as definite treatments of MDRAB pneumonia. Patients who received tigecycline were selected as potential controls for those who had received colistin. We performed a propensity score analysis, by considering the criteria of age, gender, underlying diseases, and disease severity, in order to match and equalize potential prognostic factors and severity in the two groups.. A total of 294 adults with MDRAB pneumonia were enrolled, including 119 who received colistin and 175 who received tigecycline. We matched 84 adults who received colistin with an equal number of controls who received tigecycline. The two well matched cohorts share similar characteristics: the propensity scores are colistin: 0.37 vs. tigecycline: 0.37, (P = .97); baseline creatinine (1.70 vs. 1.81, P = .50), and the APACHE II score (21.6 vs. 22.0, P = .99). The tigecycline group has an excess mortality of 16.7% (60.7% vs. 44%, 95% confidence interval 0.9% - 32.4%, P = .04). The excess mortality of tigecycline is significant only among those with MIC >2 μg/mL (10/12 vs. 37/84, P = .01), but not for those with MIC ≦ 2 μg/mL (4/10 vs. 37/84, P = .81).. Our data disfavors the use of tigecycline-based treatment in treating MDRAB pneumonia when tigecycline and colistin susceptibilities are unknown, since choosing tigecycline-based treatment might result in higher mortality. The excess mortality of tigecycline-based group may be related to higher MIC of tigecycline (> 2 μg/mL). Choosing tigecycline empirically for treating MDRAB pneumonia in the critical setting should be cautious.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia; Retrospective Studies; Taiwan; Tigecycline

To identify risk factors for the first episode of Klebsiella Pneumonia resistant to carbapenems (KPRC) infection in critically ill patients.. This prospective cohort study was conducted in a 12-bed general Intensive Care Unit (ICU) in a University Hospital on ICU patients who required mechanical ventilation (MV) for >48 hours during a 12-month period. Clinical and microbiologic data were studied. Characteristics of KPRC patients were compared with those of critically ill patients who presented nonmultidrug resistant (MDR) bacterial infections or no documented infection at all.. Twenty-five patients presented KPRC infection, 18 presented non-MDR bacterial infection, and 39 patients presented no infection. Compared to patients without documented infection or infected by non MDR bacteria, patients with KPRC infection had received more frequently or for longer duration antibiotics against Gram-negative bacteria (carbapenems, colistin P < 0.05). Duration of colistin administration prior to KPRC isolation was independently associated with increased frequency of KPRC infection (odds ratio, 1.156 per day; 95% confidence interval, 1.010 to 1.312; P = 0.025). KPRC patients stayed longer in the ICU and received mechanical ventilation and sedation for longer periods and presented increased mortality (P < 0.05).. KPRC infection is an emerging problem which might be more common in patients with previous use of antibiotics and especially colistin.

Topics: Adult; Aged; Carbapenems; Colistin; Critical Illness; Drug Resistance, Microbial; Female; Humans; Intensive Care Units; Klebsiella pneumoniae; Male; Middle Aged; Pneumonia; Prospective Studies; Risk Factors

Acinetobacter baumannii is a leading cause of multidrug-resistant infections worldwide. This organism poses a particular challenge due to its ability to acquire resistance to new antibiotics through adaptation or mutation. This study was undertaken to determine the mechanisms governing the adaptability of A. baumannii to the antibiotic colistin. Screening of a transposon mutant library identified over 30 genes involved in inducible colistin resistance in A. baumannii. One of the genes identified was lpsB, which encodes a glycosyltransferase involved in lipopolysaccharide (LPS) synthesis. We demonstrate that loss of LpsB function results in increased sensitivity to both colistin and cationic antimicrobial peptides of the innate immune system. Moreover, LpsB is critical for pathogenesis in a pulmonary model of infection. Taken together, these data define bacterial processes required for intrinsic colistin tolerance in A. baumannii and underscore the importance of outer membrane structure in both antibiotic resistance and the pathogenesis of A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacterial Proteins; Colistin; Drug Resistance, Multiple, Bacterial; Female; Glycosyltransferases; Immune Tolerance; Immunity, Innate; Lipopolysaccharides; Lung; Mannosyltransferases; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Mutation; Pneumonia

The incidence of multidrug-resistant Pseudomonas aeruginosa (MDRPA) and metallo-beta-lactamase (MBL)-producing P. aeruginosa has increased worldwide. The treatment options are limited for infectious diseases caused by these two organisms. The use of colistin has been of recent interest in cases involving both types. We report the case of a 74-year-old man with acute myeloid leukemia who was successfully treated with intravenous colistin for maxillary sinusitis and orbital cellulites due to MBL-producing MDRPA during neutropenia, and then for pneumonia caused by the bacteria after the recovery of neutrophil counts.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Leukemia, Myeloid, Acute; Male; Maxillary Sinusitis; Orbital Cellulitis; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

We present 6 cases of multidrug-resistant (MDR) Acinetobacter baumannii pneumonia in lung transplant recipients. All cases were treated with imipenem and/or non-traditional antibiotics, such as tigecycline and colistimethate, and had different microbiologic and clinical outcomes. Prior treatment with broad-spectrum anti-microbial therapy was the single most likely risk factor for the development of infection due to MDR Acinetobacter baumannii. Ideal preventive and therapeutic strategies for this pathogen in lung transplant recipients require further study.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Infective Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Lung Transplantation; Male; Minocycline; Pneumonia; Risk Factors; Tigecycline; Treatment Outcome

Acinetobacter spp. and Pseudomonas aeruginosa are common pathogens of ventilator-associated pneumonia (VAP). The presentation and outcome of VAP due to Acinetobacter spp. and P. aeruginosa susceptible to carbapenems (Carb-S; imipenem and/or meropenem) and to colistin only (Col-S) were compared in the present retrospective study in three intensive care units. A total of 61 episodes of VAP caused by Acinetobacter spp. or P. aeruginosa were studied, of which 30 isolates were Carb-S and 31 were Col-S. Demographics, worsening of renal function and mortality were not different. The univariate analysis showed that a later onset and a previous episode of VAP, prior antimicrobial therapy for >10 days and previous therapy with carbapenems during the present admission were more frequent in patients with Col-S strains. On multivariate analysis, prior antimicrobial therapy for >10 days and a previous episode of VAP remained significantly associated with Col-S VAP. Approximately 41% of the infections caused by Col-S isolates, but none of those due to Carb-S isolates, had received prior carbapenem therapy. Colistin-susceptible ventilator-associated pneumonia episodes can be effectively treated using colistin without significant renal dysfunction. This susceptibility pattern could be suspected in patients with a previous ventilator-associated pneumonia episode or prior antibiotic therapy for >10 days preceding the present ventilator-associated pneumonia episode.

Topics: Acinetobacter Infections; Analysis of Variance; Anti-Bacterial Agents; Chi-Square Distribution; Colistin; Drug Resistance, Microbial; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Respiration, Artificial; Retrospective Studies; Risk Factors; Thienamycins; Ventilators, Mechanical

The intravenous use of polymyxins has been considered to be associated with considerable nephrotoxicity and neurotoxicity. For this reason, the systemic administration of polymyxins had been abandoned for about 20 years in most areas of the world. However, the problem of infections due to multidrug-resistant (MDR) Gram-negative bacteria such us Pseudomonas aeruginosa and Acinetobacter baumanniii has led to the re-use of polymyxins. Our objective was to study the toxicity of prolonged intravenous administration of colistin (polymyxin E).. An observational study of a retrospective cohort at "Henry Dunant" Hospital, a 450-bed tertiary care center in Athens, Greece, was undertaken.Patients who received intravenous colistin for more than 4 weeks for the treatment of multidrug resistant Gram-negative infections were included in the study. Serum creatinine, blood urea, liver function tests, symptoms and signs of neurotoxicity were the main outcomes studied.. We analyzed data for 19 courses of prolonged intravenous colistin [mean duration of administration (+/- SD) 43.4 (+/- 14.6) days, mean daily dosage (+/- SD) 4.4 (+/- 2.1) million IU, mean cumulative dosage (+/- SD) 190.4 (+/- 91.0) million IU] in 17 patients. The median creatinine value increased by 0.25 mg/dl during the treatment compared to the baseline (p < 0.001) but returned close to the baseline at the end of treatment (higher by 0.1 mg/dl, p = 0.67). No apnea or other evidence of neuromuscular blockade was noted in any of these patients who received prolonged treatment with colistin.. No serious toxicity was observed in this group of patients who received prolonged intravenous colistin. Colistin should be considered as a therapeutic option in patients with infections due to multidrug resistant Gram-negative bacteria.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Biliary Tract; Cohort Studies; Colistin; Creatinine; Female; Humans; Infusion Pumps; Kidney; Liver; Liver Function Tests; Male; Middle Aged; Nervous System; Neuromuscular Junction; Pneumonia; Retrospective Studies; Time Factors; Urea

The management challenges of patients with nosocomial pneumonia are great because of resistance among the responsible pathogens. In this issue of Critical Care, Argyris Michalopoulos and colleagues describe the use of inhaled colistin in the treatment of multidrug-resistant Gram-negative nosocomial pneumonia in a small group of patients. Although seven of eight patients who received nebulized colistin showed clinical improvement, some patients also received other active antibiotics. Microbiological eradication was demonstrated in only four of the eight patients. Serum levels of colistin were not measured. In addition, although adverse events were not documented in patients receiving colistin, formal assessments for bronchoconstriction and neurological toxicity were not completed in this retrospective study. Although resistance to colistin in Gram-negative organisms has not evolved, the risk of breakthrough infection with Gram-positive and inherently resistant Gram-negative bacteria remains a concern. The results of this limited study do, however, suggest that further studies examining the use of nebulized colistin are merited.

Topics: Aerosols; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Humans; Pneumonia; Retrospective Studies

We prospectively evaluated the efficacy and toxicity of intravenously administered colistin in 35 episodes of ventilator-associated pneumonia (VAP) due to multidrug-resistant Acinetobacter baumannii. Microbiological diagnosis was performed with use of quantitative culture. In 21 patients, the episodes were caused by a strain susceptible exclusively to colistin (the CO group) and were all treated with this antimicrobial intravenously. In 14 patients, the episodes were caused by strains that remained susceptible to imipenem and were treated with imipenem-cilastatin (the IM group). Acute Physiology and Chronic Health Evaluation II scores at the time of admission and Sequential Organ Failure Assessment scores at time of diagnosis were similar in both groups. VAP was considered clinically cured in 57% of cases in both groups. In-hospital mortality rates were 61.9% in the CO group and 64.2% in the IM group, and the VAP-related mortality rates were 38% and 35.7%, respectively. Four patients in the CO group and 6 in the IM group developed renal failure. Neurophysiological evaluation was performed during 12 episodes in the CO group, but it revealed no signs of neuromuscular blockade. Intravenous colistin appears to be a safe and effective alternative to imipenem for the management of VAP due to carbapenem-resistant strains of A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple; Female; Humans; Imipenem; Infusions, Intravenous; Male; Middle Aged; Pneumonia; Prospective Studies; Renal Insufficiency; Ventilators, Mechanical

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Drug Resistance, Multiple; Drug Utilization; Humans; Pneumonia; Ventilators, Mechanical

To evaluate the efficiency of intratracheal colistin in preventing nosocomial bronchopneumonia (BPN) in the critically ill.. Study evaluating the clinical incidence of nosocomial BPN in 2 groups of critically ill patients who receive or did not receive intratracheal colistin. BPN was assessed clinically in survivors and histologically in non-survivors.. A 14-bed surgical intensive care unit.. 598 consecutive critically ill patients were studied during a prospective non-randomized study over a 40-month period.. 251 patients--31 non-survivors and 220 survivors--did not receive intratracheal colistin and 347-42 non-survivors and 305 survivors--received intratracheal colistin for a 2-week period (1,600,000 units per 24 h).. The incidence of nosocomial BPN was evaluated clinically in survivors, using repeated protected minibronchoalveolar lavages, and histologically in non-survivors via an immediate postmortem pneumonectomy (histologic and semi-quantitative bacteriologic analysis of one lung). The clinical incidence of nosocomial BPN was of 37% in coli (-) survivors and of 27% in coli (+) survivors (p < 0.01). This result was histologically confirmed in non-survivors, where the incidence of histologic BPN was of 61% in coli (-) patients and of 36% in coli (+) patients (p < 0.001). Emergence of BPN due to colistin-resistant micro-organisms was not observed. Because colistin was successful in preventing Gram-negative BPN and did not change the absolute number of Gram-positive BPN, the proportion of BPN caused by staphylococcus species was higher in group coli (+) patients (33% vs 16%). Mortality was not significantly influenced by the administration of colistin.. This study suggests that the administration of intratracheal colistin during a 2-week period significantly reduces the incidence of Gram-negative BPN without creating an increasing number of BPN due to colistin-resistant micro-organisms.

Topics: Aged; Bronchoalveolar Lavage Fluid; Colistin; Critical Illness; Cross Infection; Drug Evaluation; Drug Resistance, Microbial; Female; Gram-Negative Bacterial Infections; Humans; Incidence; Instillation, Drug; Intubation, Intratracheal; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonectomy; Pneumonia; Prospective Studies; Respiration, Artificial; Survival Rate

to evaluate the effect of the prolonged systematic use of topical SDD (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg) on ICU ecology as expressed by changes in tracheal colonization and bacterial resistances.. Prospective microbiological survey.. Polyvalent ICU of a 2000 beds general hospital.. Data concerning bacterial strains isolated from the tracheo-bronchial aspirates of all the patients admitted to a polyvalent ICU over 3 consecutive periods of 12 months ('88, '89, '90) were prospectively entered in a database and subsequently analyzed. During a 3-year period 502 patients required artificial ventilation for more than 72 h and 332 of them ('89 and '90) were treated with SDD. All samples collected within 72 h from ICU admission were excluded as well as duplicate samples from the same patients.. All the patients admitted to the ICU in '89 and '90 and submitted to artificial ventilation for at least 24 h were routinely treated with topical SDD without i.v. antibiotic prophylaxis; in '88 SDD was not employed.. Criteria for collecting sputum samples and microbiological procedures remained unchanged throughout the study-time. Positive sputum were significantly less in '89 (80.8% versus 92.3% p < 0.001) and this was due to a very sharp decrease in the isolation of Gram-negative strains from 43-28% (-64% p < 0.0001) involving both: Enterobacteriaceae (-45%) and Pseudomonaceae (-77%). In 1990; however, a new increase in Gram negative was observed, although the overall amount of Gram-negative was still 49% lower in '90 if compared to '88 (p < 0.0001). A dramatic increase in Pseudomonas isolation was the only factor responsible for the "rebound" observed. An increasing percentage of Pseudomonas developed a resistance towards tobramycin and only 45% of Pseudomonas strains turned out to be sensible to tobramycin in '90 against 79% in '88. A similar trend was registered for all aminoglycosides with the exception of amikacin. Gram-positive colonizations tended to increase (+63%) (p < 0.0001) and this was mainly due to Coagulase negative Staphylococci (+290% p < 0.0001) and S. pneumoniae, whereas S. aureus isolations decreased (-18%) but not significantly.. Our data suggest that the prolonged use of SDD is associated with dramatic changes in ICU ecology: the incidence of Gram negative colonization is significantly diminished by SDD whereas Gram positive tend to increase. Pseudomonas developed an increasing resistance towards tobramycin one of the components of the SDD formula we used.

Topics: Administration, Oral; Administration, Topical; Amphotericin B; Bronchi; Colistin; Colony Count, Microbial; Cross Infection; Drug Resistance, Microbial; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Incidence; Infection Control; Intensive Care Units; Intubation, Gastrointestinal; Pneumonia; Respiration, Artificial; Sputum; Tobramycin; Trachea

Four blood isolates, 12 pneumonia isolates, and seven colonizing isolates of Branhamella catarrhalis were compared with respect to their ability to grow in normal human serum and in convalescent serum of a patient with B. catarrhalis bacteremia. Disease-causing isolates showed seven of 16 serum-resistant strains (43 percent) compared with one of seven (13 percent) colonizing strains. Bacteremic strains were not more serum-resistant than pneumonia-causing strains. Trypsin zones of inhibition were higher for disease-causing strains. There was no correlation between source of isolation and colistin sensitivity or ability to hemagglutinate red blood cells.

Topics: beta-Lactamases; Blood Bactericidal Activity; Colistin; Hemagglutination Tests; Humans; Moraxella catarrhalis; Phenotype; Pneumonia; Sputum; Trypsin

Colonization of the oropharynx with potentially pathogenic microorganisms (PPM) is a highly significant factor in the pathogenesis of bacterial pneumonia in intensive care patients. Via colonization of the oropharynx, bacteria pass into the tracheobronchial tree, where they can give rise to pneumonia after overcoming pulmonary resistance mechanisms. By a new, prophylactic antibiotic treatment schedule consisting in selective decontamination of the digestive tract (SDD) with locally applied nonabsorbable antibiotics, Stoutenbeek achieved drastic lowering of the colonization and infection rate in trauma patients. In the present study, we wanted to check whether this new prophylactic antibiotic schedule can be applied on a surgical intensive care ward in all patients with long-term ventilation, irrespective of the diagnosis, and whether it affords advantages over a conventional antibiotic schedule. MATERIALS AND METHODS. All patients on a surgical intensive care ward in whom it was expected that mechanical ventilation would be necessary for more than 4 days were included in the study. During the first 6 months 83 patients were investigated, in whom antibiotics were only administered when the presence of infection had been confirmed, in accordance with generally accepted guidelines (control group). In the second 6-month period, 82 patients were selectively decontaminated with 4 x 100 mg polymyxin E, 4 x 80 mg tobramycin and 4 x 500 mg amphotericin B, administered through the gastric tube and in an antimicrobial paste in the oropharynx (SDD group). The SDD schedule entailed systemic administration of cefotaxime in the first 3-4 days. RESULTS. In the control group, enterobacteria/Pseudomonas spp. were isolated significantly more frequently than in the SDD group (P less than 0.001): in the pharyngeal smear in up to 53%, in the tracheal secretion up to 36%, and in the rectal smear in up to 93% of the patients In the SDD group in the 1 week the frequency of gram-negative aerobic bacteria in the pharynx decreased from 33% to 5%, in the tracheal secretion from 23% to 14% and in the rectum from 86% to 52% (24% in the second week). However, the decrease in gram-negative microorganisms was accompanied by significant increase in the frequency of Staphylococcus epidermidis and enterococci. The SDD schedule proved to be effective with regard to the rate of infection. In the control group, 35 patients developed pneumonia (42%) as against 5 patients receiving SDD prophylaxi

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Bacteria; Cefotaxime; Colistin; Critical Care; Digestive System; Female; Humans; Male; Middle Aged; Oropharynx; Pneumonia; Respiration, Artificial; Time Factors; Tobramycin

We report the results of a prophylactic regime designed to prevent endogenous colonization and infection of the lower airways by Gram-negative bacilli. The 27 study patients spent an average of 30 days (range 11 to 84) in the respiratory ICU, during which time they were on mechanical ventilation. Within 3 days of application of 2% polymyxin E and tobramycin in an adhesive paste to the buccal mucosa, the oral cavity of each patient was free of Gram-negative bacilli, and subsequently, no patient developed tracheal aspirates containing Gram-negative bacilli, and no study patient developed nosocomial pneumonia.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Colistin; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Humans; Male; Middle Aged; Pneumonia; Prospective Studies; Respiration, Artificial; Respiratory System; Respiratory Tract Infections; Tobramycin

The bacteriological effect of chemotherapy against Pseudomonas aeruginosa (Ps.ae.) in lungs of patients with cystic fibrosis is reviewed. During a 5-year period 49 children and adults were treated with 190 courses of different antibiotics. The mucoid strains of Ps.ae. disappeared in 72.0% of the courses in which a combination of tobramycin and carbenicillin was employed. Tobramycin given alone had only bacteriological effect in 26.6% of the courses. Colimycin alone or in combination with carbenicillin had no effect. In 18 patients who received subsequent courses of tobramycin and combination of tobramycin and carbenicillin a significant difference in favour of the combination therapy was found, also in cases with many precipitins against Ps.ae. in serum. In 74.5% of the initially successful courses the patients were recolonized with Ps.ae. within 1 month. No nephrotoxic or ototoxic side effects were demonstrated in spite of the high doses of tobramycin (10 mg/kg/24 h) emmployed and the repeated courses.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Carbenicillin; Child; Child, Preschool; Chronic Disease; Colistin; Cystic Fibrosis; Drug Evaluation; Drug Therapy, Combination; Female; Gentamicins; Humans; Infant; Male; Pneumonia; Precipitins; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

Topics: Administration, Topical; Animals; Burns; Colistin; Cross Infection; Disease Models, Animal; Drug Resistance, Microbial; Ecthyma; Enterobacteriaceae; gamma-Globulins; Gentamicins; Humans; Pneumonia; Providencia; Pseudomonas; Pseudomonas Infections; Rats; Sepsis; Simplexvirus; Sulfonamides; Surgical Wound Infection; Thrombophlebitis; Time Factors

Topics: Carbenicillin; Colistin; Ecthyma; Gentamicins; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Meningitis; Neutropenia; Pneumonia; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Uremia

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteria; Cephalothin; Colistin; Female; Humans; Kanamycin; Male; Middle Aged; Pneumonia; Sepsis; Urinary Tract Infections

Topics: Acute Kidney Injury; Adolescent; Adult; Age Factors; Aged; Apnea; Body Weight; Colistin; Drug Hypersensitivity; Female; Follow-Up Studies; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Nausea; Nervous System Diseases; Paresthesia; Pneumonia; Prospective Studies; Pyelonephritis; Respiratory Insufficiency; Sepsis; Sex Factors; Statistics as Topic; Time Factors; Vomiting

Topics: Adult; Aged; Alcoholism; Anti-Bacterial Agents; Cephalothin; Chloramphenicol; Colistin; Female; Humans; Kanamycin; Klebsiella; Klebsiella Infections; Lung; Male; Middle Aged; Penicillin Resistance; Penicillins; Pneumonia; Polymyxins; Radiography; Sputum; Streptomycin

Topics: Adult; Aged; Colistin; Female; Humans; Lung; Male; Middle Aged; Pneumonia; Polymyxins; Pseudomonas Infections

Topics: Aged; Ampicillin; Candida; Carbon Dioxide; Cephalothin; Colistin; Drainage; Dyspnea; Enterococcus faecalis; Humans; Kanamycin; Klebsiella; Lung; Male; Oxygen; Partial Pressure; Pleural Effusion; Pneumonia; Pneumothorax; Pseudomonas aeruginosa; Pulmonary Emphysema; Radiography; Respiratory Function Tests; Sputum

Topics: Ampicillin; Colistin; Communicable Diseases; Humans; Infant, Newborn; Infant, Newborn, Diseases; Meningitis; Oxacillin; Pneumonia; Pseudomonas Infections; Pyoderma; Sepsis

Topics: Abscess; Amphotericin B; Brain Abscess; Candidiasis; Carrier State; Child; Chloramphenicol; Colistin; Deoxyribonucleases; DNA; Empyema; Enteritis; Humans; Kanamycin; Meningitis; Methicillin; Penicillins; Peritonitis; Phlebitis; Pneumonia; Pneumothorax; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Sulfadiazine; Troleandomycin

Topics: Administration, Intravenous; Blood Chemical Analysis; Colistin; Creatine; Creatinine; Humans; Injections, Intramuscular; Injections, Intravenous; Kidney Function Tests; Nitrogen; Pharmacology; Pneumonia; Probenecid; Pseudomonas Infections; Pyelonephritis; Sodium; Urea

Topics: Abscess; Cellulitis; Colistin; gamma-Globulins; Humans; Infections; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Methicillin; Neoplasms; Pharmacology; Pneumonia; Prednisone; Sepsis; Sinusitis; Statistics as Topic; Urinary Tract Infections

Topics: Abscess; Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Colistin; Dermatologic Agents; Erythromycin Ethylsuccinate; Lung Abscess; Pneumonia; Rats

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Colistin; Erythromycin Ethylsuccinate; Neomycin; Pneumonia