colistin and Gram-Positive-Bacterial-Infections

The widespread use of antibiotics has been associated with the emergence of antimicrobial resistance among bacteria. 'ESKAPE' (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acintobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) pathogens play a major role in the rapidly changing scenario of antimicrobial resistance in the 21st century. Chloramphenicol is a broad spectrum antibiotic that was abandoned in developed countries due to its association with fatal aplastic anemia. However, it is still widely used in the developing world. In light of the emerging problem of multi-drug resistant pathogens, its role should be reassessed. Our paper reviews in vitro data on the activity of chloramphenicol against ESKAPE pathogens. Susceptibility patterns for Gram-positives were good, although less favorable for Gram-negatives. However, in combination with colistin, chloramphenicol was found to have synergistic activity. The risk-benefit related to chloramphenicol toxicity has not been analyzed. Therefore, extra precautions should be taken when prescribing this agent.

Topics: Acinetobacter baumannii; Anemia, Aplastic; Anti-Bacterial Agents; Chloramphenicol; Colistin; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Enterobacter; Enterococcus faecium; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Klebsiella pneumoniae; Pseudomonas aeruginosa; Staphylococcus aureus

One hundred and eighteen (118) episodes of bacteremia and fungemia in children with cancer were compared to 401 episodes of bacteremia and fungemia in adults with cancer to assess differences in etiology, risk factors and outcome. A retrospective univariate analysis was performed of all episodes of bacteremia in national pediatric and adult cancer institutions appearing in 1990-1996. A total of 519 episodes of bacteremia were assessed and compared. Both cancer centers differed in prophylactic antibiotic policies. About 50% of adults but less than 5% of children received quinolone prophylaxis during neutropenia, even though the empiric antibiotic therapeutic strategy was similar. There were differences in etiology between the groups: staphylococci and Stenotrophomonas maltophilia were more frequently observed in children (P<0.01), Pseudomonas aeruginosa and Acinetobacter spp. in adults (P<0.05). Gram-positive bacteremia was surprisingly more commonly observed in adults (65.7% vs 33.3%, P<0.01). Mixed polymicrobial bacteremia occurred more commonly in adults (31.8% vs 7.6%, P<0.001) than in children. Analysis of risk factors did not observe differences in risk factors except for underlying disease (acute leukemia was more frequently observed in children -48.3% vs adults 33.7%, P<0.05 and prophylaxis: (prior prophylaxis with quinolones was more common in adults (47.5%) than in children (2.5%) P<0.0001). Overall and attributable mortality in pediatric bacteremia was significantly lower than in adults (P<0.03).

Topics: Adult; Analysis of Variance; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Agents; Bacteremia; Child; Colistin; Fluconazole; Fungemia; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Neoplasms; Neutropenia; Ofloxacin; Penicillin V; Penicillins; Retrospective Studies; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Coinfection; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterococcus faecalis; Enterococcus faecium; Eye Neoplasms; Febrile Neutropenia; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Klebsiella Infections; Leukemia, Myeloid, Acute; Male; Melanoma; Meropenem; Middle Aged; Neoplasms, Second Primary; Pseudomonas Infections; Tigecycline

Physicians are facing a worldwide increase in multidrug-resistant (MDR) organisms. Eradication of such bacteria, including so called superbugs (XDR), may cause physicians to prescribe last-resort antibiotics. However, experience with these drugs is limited and few data are available.. A before and after retrospective study was conducted from January 2008 to June 2016. Prescriptions of parenteral antimicrobials considered as last-resort antibiotics (colistin, fosfomycin, tigecycline and temocillin) were reviewed by 4 infectious disease specialists (according to microbiology results, susceptibility testing, clinical situation and alternative agents), while doses were analysed by a pharmacist. As a second step, the cohort was split before and after 2013 coinciding with the arrival of a referent in antimicrobial stewardship.. The treatment of 77 patients with a mean age of 55.4 ± 18.7 years was analysed. The majority were treated for gram-negative rods (69.2%), especially Pseudomonas and Klebsiella spp. and Escherichia coli while 20.0% of patients were treated for gram-positive cocci (mainly Staphylococcus aureus) and the remainder were polymicrobial. Of 84 prescriptions, fosfomycin was the most frequently prescribed (47.6%), followed by colistin (40.5%), tigecycline (10.7%) and temocillin (1.2%). Outcomes were favorable in 75.3% of patients. In patients with MDR and XDR infections (n = 54), the mortality rate was 11.1%. After 2013, there were significantly fewer prescriptions of last-resort antibiotics for susceptible microorganisms (29.2% vs 6.9%), in the absence of supporting microbiology results (22.9% vs 3.5%) and fewer dose errors (56.2% vs 27.6%) (P = 0.02).. Reinforcement of the antimicrobial stewardship task force seems to be valuable for promoting the better use of last-resort antibiotics.

Topics: Adult; Advisory Committees; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antimicrobial Stewardship; Colistin; Female; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome

Antibiotic-resistant bacterial infection is one of the most serious clinical problems worldwide. Vancomycin, teicoplanin, daptomycin, and colistin are glycopeptide and lipopeptide antibiotics that are frequently used to treat multidrug-resistant bacterial infections. Therapeutic drug monitoring is recommended to ensure both safety and efficacy and to improve clinical outcomes. This study developed a fast, simple, and sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of the concentrations of these four drugs in human plasma. The sample preparation process includes a simple protein denaturation step using acetonitrile, followed by an 11-fold dilution with 0.1% formic acid. Eight target peaks for the four drugs can be analyzed within 3 min using a Kinetex™ 2.6 μm C18 column. The mass spectrometry parameters were optimized, and two transitions for each target peak were used for multiple reaction monitoring, which provided high sensitivity and specificity. The UHPLC-MS/MS method was validated over clinical concentration ranges. The intra-day and inter-day precisions for the ratio of the peak area of each analyte to the peak area of the internal standard were all below 12.7 and 14.7% relative standard deviations, respectively. The accuracy at low, medium, and high concentrations of the eight target peaks was between 89.3 and 110.7%. The standard curves for the analytes were linear and had coefficients of determination higher than 0.997. The limits of detection were all below 70 ng mL(-1). The use of this method to analyze patient plasma samples confirmed that it is effective for the therapeutic drug monitoring of these four drugs and can be used to improve the therapeutic efficacy and safety of treatment with antibiotics.

Topics: Acetonitriles; Anti-Bacterial Agents; Calibration; Chromatography, High Pressure Liquid; Colistin; Daptomycin; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Formates; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Limit of Detection; Protein Denaturation; Reproducibility of Results; Tandem Mass Spectrometry; Teicoplanin; Vancomycin

Enterobacter cloacae is an important nosocomial pathogen responsible for various infections. Little is known about the synergistic effects of imipenem and colistin against multidrug-resistant E. cloacae. Therefore, we investigated the in vitro effects of imipenem and colistin against a clinical isolate of multidrug-resistant E. cloacae.. A strain of E. cloacae, designed Ent 831, was isolated from the sputum of a woman who developed severe pneumonia in a medical intensive care unit. Minimal inhibitory concentrations (MICs) of imipenem and colistin were determined by the agar dilution method. The synergistic effects were investigated using the time-kill method.. MICs of imipenem and colistin for E. cloacae strain Ent 831 were 0.5 microg/mL and 1.0 microg/mL, respectively. Using a standard inoculum (5 x 10(5)) CFU/mL), synergism was shown with a concentration of two times the MICs of imipenem and colistin. Furthermore, four times the MIC of imipenem completely inhibited bacterial growth for more than 48 hours, but four times the MICs of colistin resulted in re-growth after 4 hours. There was no synergism between imipenem and colistin at two times the MICs against a high concentration inoculum (6.24 x 10(6)) CFU/mL). Nevertheless, imipenem, with or without colistin, at a concentration of four times MICs could inhibit the growth of bacteria for more than 48 hours.. High-dose imipenem, alone or in combination with colistin, is effective against multidrug-resistant E. cloacae. Colistin alone, even at a high dose, is not effective. However, in vitro susceptibility to antimicrobial compounds does not always correlate with clinical success. Thus further testing of these antibiotic combinations in animal models is needed in order to predict their suitability for clinical use.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Enterobacter cloacae; Female; Gram-Positive Bacterial Infections; Humans; Imipenem; Microbial Sensitivity Tests; Microbial Viability; Middle Aged; Pneumonia, Bacterial; Sputum; Time Factors

Topics: Anti-Bacterial Agents; Cerebral Ventricles; Colistin; Gram-Positive Bacterial Infections; Humans; Injections, Intraventricular; Postoperative Complications; Safety