colistin and Sepsis

We aimed to describe the effect of aminoglycosides and tigecycline to reduce the mortality in colistin- and carbapenem-resistant Klebsiella pneumoniae (ColR-CR-Kp) infections. We included the studies with defined outcomes after active or non-active antibiotic treatment of ColR-CR-Kp infections. The active treatment was defined as adequate antibiotic use for at least 3 days (72 h) after the diagnosis of ColR-CR-Kp infection by culture. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and the checklist of PRISMA 2020 was applied. Crude and adjusted odds ratios (OR) with 95% confidence interval (CI) were calculated and pooled in the random effects model. Adding aminoglycosides to the existing treatment regimen reduced overall mortality significantly (OR 0.34, 95% CI 0.20-0.58). Overall mortality was 34% in patients treated with aminoglycoside-combined regimens and was 60% in patients treated with non-aminoglycoside regimens. Treatment with tigecycline is not found to reduce mortality (OR: 0.76, 95% CI: 0.47-1.23). Our results suggest that aminoglycoside addition to the existing regimen of colistin- and carbapenem-resistant Klebsiella pneumoniae infections reduces mortality significantly.

Topics: Aminoglycosides; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Sepsis; Tigecycline

Several clinicians use ceftazidime-avibactam (CAZ-AVI) to treat bloodstream infections (BSIs) due to carbapenem-resistant

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Carbapenems; Ceftazidime; Colistin; Drug Combinations; Humans; Microbial Sensitivity Tests; Sepsis

Colistin, an old cationic polypeptide antibiotic, have been reused due to rising incidence of infections caused by multi-drug resistant (MDR) Gram-negative microorganisms and the lack of new antibiotics. Therefore, we evaluated safety and efficacy of colistin in treatment of these infections. This study included 104 critically ill children with a median age of 55,9 months between January 2011 and January 2016. Nephrotoxicity occurred in 11 (10.5%) patients. Nephrotoxicity occurred between the third and seventh day of treatment in 63% of colistin induced nephrotoxicity episodes. The subgroup analysis between the patients who developed nephrotoxicity during colistin treatment and those that did not, showed no significant difference in terms of age, underlying disease, cause for PICU admission and type of infection required colistin treatment, P values were 0.615, 0.762, 0.621, 0.803, respectively. All patients were receiving a concomitant nephrotoxic agent (P = 0,355). The majority of the patients (52%) were having primary or secondary immune deficiency in treatment failure group and the most common cause of PICU admission was sepsis in treatment failure group, P values were 0.007 and 0.045, respectively. Mortality attributed to colistin failure and crude mortality were 14.4% and 29.8%, respectively. In conclusion, colistin may have a role in the treatment of infections caused by multidrug-resistant Gram-negative bacteria in critically ill children. However, the patients have to be followed for side effects throughout colistin treatment, not for only early stage. And the clinicians should be aware of increase in the rate of nephrotoxicity in patients those have been receiving a concomitant nephrotoxic agent.

Topics: Administration, Intravenous; Child, Preschool; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Immunologic Deficiency Syndromes; Intensive Care Units, Pediatric; Kidney; Referral and Consultation; Retrospective Studies; Sepsis; Treatment Outcome

The objective of this study was to describe the microbiological characteristics of an extensively drug-resistant (XDR) isolate of Morganella morganii obtained from a patient with sepsis of urinary origin and to describe the patient's clinical characteristics. We further aimed to perform a literature review of the situation in Latin America regarding Gram-negative bacillus (GNB) carriers of New Delhi metallo-β-lactamase (NDM-1) and qnr genes and current reports on the treatment of infections caused by XDR enterobacteria, with particular attention to colistin-resistant isolates.. The patient's clinical data were obtained from his medical history. Microbiological identification and susceptibility testing were done using the VITEK 2 Compact System. Resistance genes were detected by PCR and sequencing.. Blood and urine cultures grew an M. morganii isolate (Mm4232) harboring NDM-1 and qnrD1. The patient was treated successfully with fosfomycin and double doses of meropenem. There are no previous reports of the use of fosfomycin and meropenem to treat infections by XDR enterobacteria harboring NDM-1 carbapenemase.. This is the first report of qnrD1 in South America. We consider that this report could be helpful to physicians implementing treatments for infections caused by XDR GNB, including colistin-carbapenem-resistant GNB.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae Infections; Fosfomycin; Humans; Male; Meropenem; Morganella morganii; Sepsis; South America; Thienamycins; Young Adult

Critical illness, acute renal failure and continuous renal replacement therapy (CRRT) are associated with changes in pharmacokinetics. Initial antibiotic dose should be based on published volume of distribution and generally be at least the standard dose, as volume of distribution is usually unchanged or increased. Subsequent doses should be based on total clearance. Total clearance varies with the CRRT clearance which mainly depends on effluent flow rate, sieving coefficient/saturation coefficient. As antibiotic clearance by healthy kidneys is usually higher than clearance by CRRT, except for colistin, subsequent doses should generally be lower than given to patients without renal dysfunction. In the future therapeutic drug monitoring, together with sophisticated pharmacokinetic models taking into account the pharmacokinetic variability, may enable more appropriate individualized dosing.

Topics: Anti-Bacterial Agents; Colistin; Daptomycin; Drug Monitoring; Humans; Renal Insufficiency; Renal Replacement Therapy; Sepsis

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Biliary Tract Diseases; Carbenicillin; Cephalosporins; Chloramphenicol; Colistin; Endocarditis, Subacute Bacterial; Gentamicins; Humans; Meningitis; Osteomyelitis; Oxacillin; Sepsis; Tetracycline; Urinary Tract Infections

Topics: Chloramphenicol; Colistin; Dihydrostreptomycin Sulfate; Drug Synergism; Endocarditis, Subacute Bacterial; Hearing Disorders; Humans; Kanamycin; Penicillin Resistance; Penicillins; Polymyxins; Sepsis; Streptococcal Infections; Streptomycin; Tetracycline; Vestibulocochlear Nerve

An urgent need exists for antibiotics to treat infections caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC). Sulbactam-durlobactam is a β-lactam-β-lactamase inhibitor combination with activity against Acinetobacter, including multidrug-resistant strains. In a phase 3, pathogen-specific, randomised controlled trial, we compared the efficacy and safety of sulbactam-durlobactam versus colistin, both in combination with imipenem-cilastatin as background therapy, in patients with serious infections caused by carbapenem-resistant ABC.. The ATTACK trial was done at 59 clinical sites in 16 countries. Adults aged 18 years or older with ABC-confirmed hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bloodstream infections were randomised 1:1 using a block size of four to sulbactam-durlobactam (1·0 g of each drug in combination over 3 h every 6 h) or colistin (2·5 mg/kg over 30 min every 12 h) for 7-14 days. All patients received imipenem-cilastatin (1·0 g of each drug in combination over 1 h every 6 h) as background therapy. The primary efficacy endpoint was 28-day all-cause mortality in patients with laboratory-confirmed carbapenem-resistant ABC (the carbapenem-resistant ABC microbiologically modified intention-to-treat population). Non-inferiority was concluded if the upper bound of the 95% CI for the treatment difference was less than +20%. The primary safety endpoint was incidence of nephrotoxicity assessed using modified Risk, Injury, Failure, Loss, End-stage renal disease criteria measured by creatinine level or glomerular filtration rate through day 42. This trial is registered at ClinicalTrials.gov, NCT03894046.. Between Sep 5, 2019, and July 26, 2021, 181 patients were randomly assigned to sulbactam-durlobactam or colistin (176 hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, or ventilated pneumonia; and five bloodstream infections); 125 patients with laboratory-confirmed carbapenem-resistant ABC isolates were included in the primary efficacy analysis. 28-day all-cause mortality was 12 (19%) of 63 in the sulbactam-durlobactam group and 20 (32%) of 62 in the colistin group, a difference of -13·2% (95% CI -30·0 to 3·5), which met criteria for non-inferiority. Incidence of nephrotoxicity was significantly (p<0·001) lower with sulbactam-durlobactam than colistin (12 [13%] of 91 vs 32 [38%] of 85). Serious adverse events were reported in 36 (40%) of 91 patients in the sulbactam-durlobactam group and 42 (49%) of 86 patients in the colistin group. Treatment-related adverse events leading to study drug discontinuation were reported in ten (11%) of 91 patients in the sulbactam-durlobactam group and 14 (16%) of 86 patients in the colistin group.. Our data show that sulbactam-durlobactam was non-inferior to colistin, both agents given in combination with imipenem-cilastatin, for the primary endpoint of 28-day all-cause mortality. Sulbactam-durlobactam was well tolerated and could be an effective intervention to reduce mortality from serious infections caused by carbapenem-resistant ABC, including multidrug-resistant strains.. Entasis Therapeutics and Zai Lab.

Topics: Acinetobacter baumannii; Adult; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cilastatin, Imipenem Drug Combination; Colistin; Humans; Microbial Sensitivity Tests; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sepsis

The previously described anti-endotoxin effect of colistin has not been investigated in humans yet. We performed a randomized, double-blind, placebo-controlled crossover trial to determine the degree of colistin-driven modulation of inflammatory response in blood of lipopolysaccharide (LPS)-challenged healthy volunteers in a human endotoxemia model. After a single intravenous dose of 2.5 million IU colistin methanesulfonate, interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-α), and IL-1β concentrations as well as other biomarkers of inflammation such as C-reactive protein, differential leukocyte counts, and body temperature were measured up to 24 h postdose. Colistin significantly decreased the inflammatory cytokine response to LPS in blood of healthy volunteers. This effect was most evident for IL-6, IL-8, and TNF-α. This study is the first to confirm the anti-endotoxin effect of colistin in humans in vivo. Further studies might increase our knowledge on the interaction between colistin and the effectors of the immune system.

Topics: Adult; Anti-Inflammatory Agents; Biomarkers; Body Temperature Regulation; C-Reactive Protein; Colistin; Cross-Over Studies; Cytokines; Double-Blind Method; Endotoxemia; Healthy Volunteers; Humans; Inflammation; Inflammation Mediators; Infusions, Intravenous; Lipopolysaccharides; Male; Sepsis; Time Factors; Treatment Outcome

The emergence of multidrug-resistant nosocomial pathogens, such as Pseudomonas aeruginosa and Acinetobacter baumannii, has led to the revival of the systemic use of antimicrobial agent colistin in critically ill patients, but only limited data are available to define its pharmacokinetic profile in these patients.. The aim of this study was to assess steady-state serum concentrations of colistin after i.v. administration of colistin methanesulfonate (CMS) in critically ill patients with stable kidney function.. This prospective, open-label, uncontrolled study was conducted at 2 intensive care units in the Athens Trauma Hospital, KAT, Athens, Greece. Adult patients were nonconsecutively enrolled if they were critically ill and had stable kidney function (<0.5 mg/dL change in serum creatinine prior to and until the day of sample collection) and had been receiving CMS as part of a treatment regimen for sepsis irrespective of site of infection with multidrug-resistant, gram-negative bacilli. After i.v. administration of 225-mg CMS (with the exception of 1 patient who received 150 mg) every 8 or 12 hours for at least 2 days, blood samples were collected just before and at 10 minutes and 1, 2, 4, 6, and 8 hours after i.v. infusion (duration, 30 minutes) of the colistin dose on the sampling day.. Fourteen nonconsecutive patients were enrolled in the study (13 male, 1 female; mean [SD] age, 62.0 [19.2] years; mean [SD] estimated weight, 72.5 [8.5] kg; mean [SD] Acute Physiology And Chronic Health Evaluation II score on admission, 17.1 [6.0]). At steady state, mean (SD) colistin maximum and minimum concentrations were 2.93 (1.24) and 1.03 (0.44) mg/L, respectively, while mean (SD) apparent total body clearance, apparent volume of distribution, and t(1/2) were 13.6 (5.8) L/h, 139.9 (60.3) L, and 7.4 (1.7) hours, respectively. Colistin-related nephrotoxicity was not observed in the study patients.. CMS dosage regimens administered to these critically ill adult patients were associated with suboptimal Cmax/MIC ratios for many strains of gram-negative bacilli currently reported as sensitive (MIC, < or = 2 microg/mL).

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intravenous; Intensive Care Units; Male; Middle Aged; Prospective Studies; Pseudomonas Infections; Sepsis

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

Topics: Acinetobacter baumannii; Adult; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple; Female; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Male; Middle Aged; Pseudomonas aeruginosa; Sepsis

Three gastrointestinal tract decontamination regimens were tested in patients with granulopenia: vancomycin 250 mg, tobramycin 75 mg, and colistin 1 million international units (regimen A); vancomycin 125 mg, tobramycin 75 mg, and colistin 1 million IU (regimen B); and colistin 1 million IU (regimen C); nystatin was added to all three regimens. Effectiveness was evaluated by stool organism counts and blood cultures to detect bacterial translocation (passage of bacteria from the intestinal tract to the bloodstream). Regimen C proved insufficiently effective. Regimen A was found to be poorly tolerated by the digestive mucosa. Regimen B was the best treatment since the low dosage of vancomycin proved effective. Nystatin satisfactorily eliminated yeasts.

Topics: Agranulocytosis; Colistin; Drug Therapy, Combination; Gastrointestinal Diseases; Humans; Nystatin; Sepsis; Tobramycin; Vancomycin

To study the effect of enterally administered polymyxin E, tobramycin, and amphotericin B (selective flora suppression) on bacterial colonization, infection, resistance, and mortality rate.. Prospective, consecutive crossover controlled study.. Two surgical ICUs in a university hospital; ICU I with ten beds, ICU II with eight beds.. Two hundred patients entered the 1-yr trial. Fifty of 111 patients received selective flora suppression during the first 6 months in ICU I (test group), while 61 of 111 patients served as the control group in the following 6 months. In ICU II, 49 of 89 patients received no selective flora suppression in the first 6 months (control group), followed by 40 of 89 patients receiving selective flora suppression during the second 6-month period (test group).. The test group got a mixture of nonabsorbable antibiotics (paste and suspension) in the digestive tract. The control group received paste and suspension without antimicrobial agents. All 200 patients received cefotaxime during the first 4 days.. With the use of selective flora suppression, colonization with aerobic Gram-negative bacilli was significantly (p less than .01) reduced. There was also a significant reduction in nosocomial bronchopulmonary (ICU I and II; p less than .001) and urinary tract (ICU II; p less than .001) infections. The difference in mortality was not significant. There was no development of resistance against the antibiotics used during the limited period evaluated.. Selective flora suppression is effective in reducing secondary colonization by aerobic Gram-negative bacilli. Reduction of bronchopulmonary and urinary tract infections most likely occurs with colonization prevention.

Topics: Administration, Oral; Adult; Aged; Amphotericin B; Bacterial Infections; Bronchopneumonia; Colistin; Critical Care; Cross Infection; Female; Gram-Negative Aerobic Bacteria; Humans; Intensive Care Units; Male; Middle Aged; Mortality; Mouth; Ointments; Prospective Studies; Sepsis; Suspensions; Tobramycin; Urinary Tract Infections

The question to be answered in this study was: Is prophylactic selective florasuppression advantageous compared to conventional antibiotic policy as far as microbial colonisation, infection, mortality and development of resistance are concerned? A prospective, consecutive, placebo-controlled study in two ICU's was carried out during four 6-months periods. 200 patients who were intubated for at least 3 days, required intensive care for a minimum of 5 days, and belonged to either class III or IV according to the "Therapeutic Intervention Scoring System" were included in the study. They received either placebo or the prophylaxis regimen described by Stoutenbeek et al., consisting of polymyxin E, tobramycin and amphotericin B. Oropharyngeal, tracheobronchial and rectal colonisation with aerobic gram-negative bacilli markedly decreased in the test groups. The rates of nosocomial bronchopulmonary infections (ICU I and II) and urinary tract infections (ICU II) were significantly reduced. There was no significant reduction in wound infection, septicaemia and mortality rates. No development of resistance and no increase of multi-resistant strains occurred. Selective florasuppression is effective in reducing infection rates in critically ill patients without development of resistant strains.

Topics: Adult; Aged; Amphotericin B; Bacterial Infections; Bronchopneumonia; Clinical Trials as Topic; Colistin; Cross Infection; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Male; Prospective Studies; Risk Factors; Sepsis; Surgical Wound Infection; Tobramycin; Urinary Tract Infections

Topics: Administration, Oral; Adolescent; Adult; Aged; Agranulocytosis; Antineoplastic Agents; Clinical Trials as Topic; Colistin; Gentamicins; Humans; Leukemia; Middle Aged; Neutropenia; Nystatin; Sepsis; Vancomycin

113 patients being treated for acute non-lymphoblastic leukaemia were investigated to determine the effect of suppression of body microbial flora on prevention of infection. They were randomly allocated to a control group or a group which received non-absorbed antibiotics by mouth and topical applications of cutaneous and mucosal antiseptic preparations. The group receiving oral non-absorbed antibiotics had significantly few infections, fewer deaths from infection, fewer pyrexial episodes, and consequently received less systemic antibiotic therapy than the controls.

Topics: Acute Disease; Administration, Oral; Administration, Topical; Adolescent; Adult; Antineoplastic Agents; Bacterial Infections; Bacteroides Infections; Chlorhexidine; Colistin; Drug Combinations; Enterobacteriaceae Infections; Framycetin; Humans; Leukemia; Nystatin; Remission, Spontaneous; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections

In this retrospective cohort study, we aimed to evaluate the incidence, risk factors and outcomes of amikacin-induced acute kidney injury (AKI) in critically ill patients with sepsis. A total of 311 patients were included in the study. Of them, 83 (26.7%) had amikacin-induced AKI. In model 1, the multivariable analysis demonstrated concurrent use of colistin (OR 25.51, 95%CI 6.99-93.05, p< 0.001), presence of septic shock during amikacin treatment (OR 4.22, 95%CI 1.76-10.11, p=0.001), and Charlson Comorbidity Index (OR 1.14, 95%CI 1.02-1.28, p=0.025) as factors independently associated with an increased risk of amikacin-induced AKI. In model 2, the multivariable analysis demonstrated concurrent use of at least one nephrotoxic agent (OR 1.95, 95%CI 1.10-3.45; p=0.022), presence of septic shock during amikacin treatment (OR 3.48, 95%CI 1.61-7.53; p=0.002), and Charlson Comorbidity Index (OR 1.12, 95%CI 1.01-1.26; p=0.037) as factors independently associated with an increased risk of amikacin-induced AKI. In conclusion, before amikacin administration, the risk of AKI should be considered, especially in patients with multiple complicated comorbid diseases, septic shock, and those receiving colistin therapy.

Topics: Acute Kidney Injury; Amikacin; Colistin; Critical Illness; Humans; Intensive Care Units; Respiration, Artificial; Retrospective Studies; Risk Factors; Sepsis; Shock, Septic

Emerging mobile colistin resistance (

Topics: Anti-Bacterial Agents; Colistin; Genomics; Humans; Klebsiella Infections; Klebsiella pneumoniae; Phylogeny; Plasmids; Sepsis

Pseudomonas aeruginosa frequently becomes resistant to aminoglycosides by the acquisition of aminoglycoside modifying enzyme (AME) genes and the occurrence of mutations in the

Topics: Aminoglycosides; Anti-Bacterial Agents; Ciprofloxacin; Colistin; Drug Resistance, Bacterial; Genomics; Gentamicins; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Tobramycin; United States

This study examines the role of mesenchymal stem cells (MSCs) in an experimental sepsis model developed with colistin-resistant Acinetobacter baumannii (CRAB).. BALB-c mice were divided into treatment groups (MSC, MSC + colistin (C)-fosfomycin (F), and C-F and control groups (positive and negative)). CRAB was administered to mice through intraperitoneal injection. Three hours later, C, F, and MSC were given intraperitoneally to the treatment groups. Colistin administration was repeated every 12 h, F administration was done every 4 h, and the second dose of MSC was administered after 48 h. Mice were sacrificed at 24 and 72 h. The bacterial load was determined as colony-forming units per gram (cfu/g). Histopathological examination was conducted on the left lung, liver, and both kidneys. IL-6 and C-reactive protein (CRP) levels in mouse sera were determined by enzyme-linked immunosorbent assay.. Among the treatment groups, the C-F group had the lowest colony count in the lung (1.24 ± 1.66 cfu/g) and liver (1.03 ± 1.08 cfu/g). The highest bacterial clearance was observed at 72 h compared to 24 h in the MSC-treated groups (p = 0.008). The MSC + C-F group showed the lowest histopathological score in the liver and kidney (p = 0.009). In the negative control group, the IL-6 level at the 24th hour was the lowest (p < 0.001). Among the treatment groups, the CRP level was the lowest in the MSC + C-F group at 24 and 72 h.. In a CRAB sepsis model, adding MSCs to a colistin-fosfomycin treatment may be beneficial in terms of reducing bacterial loads and preventing histopathological damage.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Fosfomycin; Interleukin-6; Mesenchymal Stem Cells; Mice; Microbial Sensitivity Tests; Sepsis

Topics: Animals; Anti-Bacterial Agents; Colistin; Fosfomycin; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Sepsis; Tobramycin

Bloodstream infection (BSI) caused by carbapenem-resistant P. aeruginosa (CRPA) has high mortality in hematopoietic stem cell transplant (HSCT) recipients. We performed MIC, checkerboard, time-kill assay, PFGE, PCR, and whole genome sequence and described the clinical outcome through Epi Info comparing the antimicrobial combination in vitro. Mortality was higher in BSI caused by CRPA carrying the lasB virulence gene. The isolates were 97% resistant to meropenem displaying synergistic effect to 57% in combination with colistin. Seventy-three percent of the isolates harbored bla

Topics: Adolescent; Adult; Anti-Bacterial Agents; Brazil; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Young Adult

Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Patients were divided in two study groups according to the antibiotic treatment received: cefiderocol- and colistin-containing regimens. The primary outcome was the 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. A total of 124 patients were included: 47 (37.9%) received cefiderocol, while 77 (62.1%) colistin-containing regimens. Overall, 79 (63.7%) patients had a bloodstream infection (BSI), 35 (28.5%) a ventilator-associated pneumonia (VAP) and 10 (8.1%) other infections. Thirty-day mortality was higher in patients receiving colistin- compared to those who received cefiderocol-containing regimens (55.8% versus 34%,

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Carbapenems; Cefiderocol; Cephalosporins; Colistin; Humans; Pneumonia, Ventilator-Associated; Retrospective Studies; Sepsis

Sepsis due to carbapenemase-producing and colistin-resistant

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Enterobacteriaceae; Ethiopia; Genomics; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Sepsis

Klebsiella pneumoniae is a significant infectious pathogen that causes bloodstream infections. This study aimed to genetically characterize a novel sequence type 4523 (ST4523) multidrug-resistant (MDR) K. pneumoniae strain recovered from the blood of a 79-year-old Chinese female patient with severe pneumonia and chronic obstructive pulmonary disease who ultimately died of the infection. The susceptibility testing results showed that strain 18SHX180 is nonsusceptible to cephalosporin, carbapenems, combinations of β-lactam and β-lactamase inhibitors, levofloxacin, and colistin and is only susceptible to amikacin. The phylogenetic structure showed that strain 18SHX180 belongs to a novel sequence type, ST4523, and capsule serotype K111. ST4523 is closely related to ST11, the most dominant clone of clinical carbapenem-resistant K. pneumoniae in China. ST4523 has 2 single-base variants in

Topics: Aged; Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Cephalosporins; Colistin; Female; Formaldehyde; Humans; Klebsiella Infections; Klebsiella pneumoniae; Levofloxacin; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Plasmids; Sepsis

This study aims to investigate trends in bloodstream infections and their antimicrobial susceptibility profiles over 12 years in our hospital. This retrospective study was carried out in the Bursa Uludag University Hospital, Turkey, during 2008-2019. Blood cultures from patients were performed using BACTEC System. Isolates were identified with Phoenix System until 2018 and "matrix-assisted laser desorption ionization time-of-flight mass spectrometry" (MALDI-TOF MS) in 2019. Antibiotic susceptibility testing was performed with Phoenix System. Patient data came from the BD EpiCenter™ data management system.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Coagulase; Colistin; Escherichia coli; Hospitals, University; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Retrospective Studies; Sepsis

Topics: Acinetobacter; Anti-Bacterial Agents; Cerebral Ventriculitis; Colistin; Humans; Infant, Newborn; Meningitis; Sepsis

One potential approach to address the rising threat of antibiotic resistance is through novel formulations of established drugs. We designed antibiotic cross-linked micelles (ABC-micelles) by cross-linking the Pluronic F127 block copolymers with an antibiotic itself, via a novel one-pot synthesis in aqueous solution. ABC-micelles enhanced antibiotic encapsulation while also reducing systemic toxicity in mice. Using colistin, a hydrophilic, potent ″last-resort" antibiotic, ABC-micelle encapsulation yield was 80%, with good storage stability. ABC-micelles exhibited an improved safety profile, with a maximum tolerated dose of over 100 mg/kg colistin in mice, at least 16 times higher than the free drug. Colistin-induced nephrotoxicity and neurotoxicity were reduced in ABC-micelles by 10-50-fold. Despite reduced toxicity, ABC-micelles preserved bactericidal activity, and the clinically relevant combination of colistin and rifampicin (co-loaded in the micelles) showed a synergistic antimicrobial effect against antibiotic-resistant strains of

Topics: Animals; Anti-Bacterial Agents; Bacteria; Colistin; Cyclophosphamide; Drug Resistance, Multiple, Bacterial; Female; Mice; Micelles; Microbial Sensitivity Tests; Neurotoxicity Syndromes; Poloxamer; Sepsis

Mortality due to K. pneumoniae bacteremia is on rise, particularly in regions with high rates of carbapenem and colistin resistance. We aimed to define risk factors for colistin resistance and its impact on mortality. Patients diagnosed with "carbapenem-resistant K. pneumoniae (CRKp)" bacteremia between 2014 and 2018 were divided into two groups as "colistin susceptible (ColS)" and "colistin resistant (ColR)" based on broth microdilution method. Retrospective case-control study was conducted to compare characteristics and outcomes. Multiple logistic regression model was used to define independent risk factors for acquired colistin resistance and Cox proportional hazard model for 28-day mortality. A total of 82 patients (39 ColS and 43 ColR) were included. Mean age was 61.5 years, and 50 (61%) were male. Colistin resistance was significantly increased with duration of hospital stay (p = 0.007) and prior colistin use (p = 0.007). Overall, the 28-day mortality rate was 66%. Age (p = 0.014) and colistin resistance significantly increased 28-day (p = 0.009) mortality. Microbiological response to treatment within 7 days favors survival. PFGE analysis revealed an outbreak with K. pneumoniae ST78 and ST45 clones. Patients treated with combined antimicrobials had significantly lower 28-day mortality (p = 0.045) in comparison to monotherapy. However, types of combinations did not show significant superiority on each other. Colistin resistance increases 28-day mortality in CRKp bacteremia. Although combined regimens are more effective than monotherapy, existing antibacterial combinations have no apparent superiority to each other. New treatment options are pivotal.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Proportional Hazards Models; Retrospective Studies; Sepsis

Extremely drug-resistant (XDR) Acinetobacter baumannii is a notorious and frequently encountered pathogen demanding novel therapeutic interventions. An initial monoclonal antibody (MAb), C8, raised against A. baumannii capsule, proved a highly effective treatment against a minority of clinical isolates. To overcome this limitation, we broadened coverage by developing a second antibody for use in a combination regimen. We sought to develop an additional anti-A. baumannii MAb through hybridoma technology by immunizing mice with sublethal inocula of virulent, XDR clinical isolates not bound by MAb C8. We identified a new antibacterial MAb, 65, which bound to strains in a pattern distinct from and complementary to that of MAb C8. MAb 65 enhanced macrophage opsonophagocytosis of targeted strains and markedly improved survival in lethal bacteremic sepsis and aspiration pneumonia murine models of A. baumannii infection. MAb 65 was also synergistic with colistin, substantially enhancing protection compared to monotherapy. Treatment with MAb 65 significantly reduced blood bacterial density, ameliorated cytokine production (interleukin-1β [IL-1β], IL-6, IL-10, and tumor necrosis factor), and sepsis biomarkers. We describe a novel MAb targeting A. baumannii that broadens immunotherapeutic strain coverage, is highly potent and effective, and synergistically improves outcomes in combination with antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Antibodies, Monoclonal; Biomarkers; Colistin; Cytokines; Drug Resistance, Multiple, Bacterial; Mice; Microbial Sensitivity Tests; Sepsis

Colistimethate sodium (CMS) has been postulated as the principal cause of high incidence of clinical acute kidney injury (AKI) in multidrug-resistance (MDR) septic patients with normal baseline serum creatinine (sCr) who were treated with CMS. This prospective observational study was conducted to examine the incidence and clinical outcomes of clinical and subclinical AKI in MDR septic patients receiving CMS.. Forty-two MDR septic patients with normal sCr who required CMS were included. Clinical AKI was diagnosed by increased sCr levels according to the KDIGO2012 criteria while subclinical AKI was identified by elevated levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL > 150 ng/mL) or urinary liver-type fatty-acid-binding protein (uL-FABP > 10.5 ng/mL).. Clinical AKI was noted in 47.6% of patients on day 5 and 38.1% on day 7 after initiating CMS. By using uL-FABP, subclinical AKI was observed in 45.2% and 54.8% on day 5 and 7, respectively. At baseline prior to CMS treatment, subclinical AKI was already present in 90%. The baseline uL-FABP was superior to the baseline uNGAL in early prediction of clinical AKI on day 5. The subclinical AKI patients had comparable worse outcomes as clinical AKI patients.. The incidence of subclinical AKI in MDR septic patients before CMS treatment was extremely high. The baseline uL-FABP provided the best predictive capacity of clinical AKI. The causes of clinical AKI might include the persistence of sepsis process, subclinical AKI and CMS nephrotoxicity. Proper management of subclinical AKI patients before CMS initiation should be concerned to prevent further renal damage and improve patient and renal outcomes.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Asymptomatic Diseases; Biomarkers; Colistin; Creatinine; Drug Resistance, Multiple, Bacterial; Fatty Acid-Binding Proteins; Female; Humans; Incidence; Lipocalin-2; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Sepsis; Time Factors; Treatment Outcome

Background Colistin resistance in P. aeruginosa (CRPA) is due to the appearance of superbug strains. As this pathogen gains more transferrable resistance mechanisms and continues to adapt to acquire additional resistance mechanisms during antimicrobial therapy rapidly, we face the growing threat of CRPA in bloodstream infections (BSI). This study designed to evaluate the frequency of CRPA strains producing different β-lactamases by the High-Resolution Melting Curve Analysis (HRMA) method in BSI and to characterize the different types by multilocus sequence typing (MLST).. Sixty-nine (69) P. aeruginosa isolates were collected from blood culture. MIC E-test methods examined the antimicrobial susceptibilities of the bacterial isolates. Detection of resistant strains performed by using HRMA assay.. The strains resistant to amikacin (n = 11; 15.94%) and colistin (n = 10; 14.49%) were the least abundant and the gentamicin (n = 56; 82.6%) and ciprofloxacin (n = 67; 97.10%) resistant strains were the most frequent. Also, 39 isolates (56.52%) considered as multidrug-resistant (MDR), 20 isolates (28.98%) as extensively drug resistant (XDR), and 11 isolates (15.94%) as Pandrug Resistance (PDR). Further, 32 isolates (46.37%) considered as AmpC producer, and 28 isolates (40.57%) were considered an MBL producer. According to HRMA results, the blaSPM gene was detected in 19 isolates (27.53%), blaNDM gene in 11 isolates (15.94%), blaFOX gene in 31 isolates (44.92%), mcr-1 gene in 10 isolates (14.49%), blaACC and blaVIM genes in 27 isolates (39.13%), and blaTEM gene was reported in 20 isolates (28.98%). Furthermore, P. aeruginosa PASGNDM699, ST3340, and ST235 identified in 1.44%, 11.59% and 17.39% isolates, respectively.. CRPA strains play an essential role in the spread of antibiotic resistance in BSI. Likewise, the HRMA method was sensitive and specific for the detection of superbugs. Moreover, MLST analysis of a diverse collection of P. aeruginosa from blood culture suggests that particular strains or clonal complexes are associated with antibiotic resistance profile.

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Female; Genetic Variation; Genotype; Humans; Iran; Male; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Sequence Analysis

The emergence of polymyxin resistance in carbapenem-resistant and extended-spectrum β-lactamase (ESBL)-producing bacteria is a critical threat to human health, and alternative treatment strategies are urgently required. We investigated the ability of the hydroxyquinoline analog ionophore PBT2 to restore antibiotic sensitivity in polymyxin-resistant, ESBL-producing, carbapenem-resistant Gram-negative human pathogens. PBT2 resensitized

Topics: Animals; Anti-Bacterial Agents; Bacteria; Colistin; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Proteins; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Neurodegenerative Diseases; Pharmaceutical Preparations; Sepsis

The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB).. Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed.. A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52-73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24-8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69-13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17-0.88; P =  0.024) was associated with use of colistin monotherapy.. Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.

Topics: Administration, Intravenous; Aged; Anti-Bacterial Agents; Colistin; Cross-Sectional Studies; Drug Prescriptions; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Endemic Diseases; Female; Gram-Negative Bacterial Infections; Humans; Italy; Male; Middle Aged; Respiratory Tract Infections; Sepsis

This study aimed to determine potential host-, pathogen-, infection- and treatment-related risk factors that might predict a fulminant fatal course of bacteraemia caused by extensively drug-resistant Acinetobacter baumannii (XDR-Aba).. Eighty-seven patients with monomicrobial growth of XDR-Aba in blood cultures within a 6-year period (2011-2016) were studied. Patients were divided into three groups according to ICU outcome: Group A (n=40) consisted of patients who survived; Group B (n=10) included patients with fulminant sepsis who died early (≤48h); and Group C (n=37) included patients who died later (>48h) after the onset of bacteraemia.. Regarding patient co-morbidities, patients who died from fulminant XDR-Aba bacteraemia had a significantly higher prevalence of chronic renal failure compared with patients who survived (40.0% vs. 7.5%; P=0.029). Patients with fulminant sepsis showed more severe organ dysfunction based on SOFA score compared with survivors (10.83±2.93 vs. 6.65±3.6; P=0.013). The primary to secondary bacteraemia ratio and appropriate treatment were similar among the three outcome groups. Patients with fulminant bacteraemia displayed higher rates of colistin-, tigecycline- and pandrug-resistant strains, although not statistically significant.. Patients suffering from a fulminant course of XDR-Aba bacteraemia showed significantly higher rates of chronic renal failure and multiple organ dysfunction. Resistance patterns of XDR-Aba isolates and receipt of appropriate treatment did not affect outcomes. Further studies including larger samples of patients along with investigation of specific virulence determinants of individual Aba strains are needed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Risk Factors; Sepsis

This study aimed to assess the predictors of acute kidney injury (AKI) during colistin therapy in a cohort of patients with bloodstream infections (BSI) due to colistin-susceptible Gram-negative bacteria, focusing on the role of serum albumin levels. The study consisted of two parts: (1) a multicentre retrospective clinical study to assess the predictors of AKI during colistin therapy, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria; and (2) bioinformatic and biochemical characterization of the possible interaction between human serum albumin and colistin. Among the 170 patients included in the study, 71 (42%), 35 (21%), and 11 (6%) developed KDIGO stage 1 (K1-AKI), KDIGO stage 2 (K2-AKI), and KDIGO stage 3 (K3-AKI), respectively. In multivariable analyses, serum albumin <2.5 g/dL was independently associated with K1-AKI (subdistribution hazard ratio [sHR] 1.85, 95% confidence interval [CI] 1.17-2.93, p = 0.009) and K2-AKI (sHR 2.37, 95% CI 1.15-4.87, p = 0.019). Bioinformatic and biochemical analyses provided additional information nurturing the discussion on how hypoalbuminemia favors development of AKI during colistin therapy. In conclusion, severe hypoalbuminemia independently predicted AKI during colistin therapy in a large cohort of patients with BSI due to colistin-susceptible Gram-negative bacteria. Further study is needed to clarify the underlying causal pathways.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Computational Biology; Female; Humans; Hypoalbuminemia; Incidence; Male; Models, Molecular; Molecular Conformation; Retrospective Studies; Sepsis; Serum Albumin, Human; Severity of Illness Index; Structure-Activity Relationship

Empiric antimicrobial therapy (EAMT) using imipenem/colistin is commonly prescribed as a first line therapy in critically ill patients with severe sepsis. We aimed to assess the appropriateness of prescribing imipenem/colistin as EAMT in ICU patients.. A 3-year observational prospective study included ICU patients that required imipenem/colistin as EAMT. The EAMT was assessed according to microbiological and clinical outcomes. The outcomes were: delay in apyrexia, delay in the decrease of the biological inflammatory parameters (BIP), the requirement for vasoactive agents, bacteriological eradication, length of stay, ventilator days and 30-day mortality.. 79 administrations of EAMT in 70 patients were studied. EAMT was appropriate in 52% of the studied cases. An ICU stay > 6 days was related to inappropriateness, and chronic respiratory failure was associated with appropriateness. In the appropriate EAMT group, we showed: earlier apyrexia, shorter delay in the decrease of the BIP and a reduced significant vasopressors requirement. Furthermore, EAMT improved survival with a median gain of 4 days. Inappropriate EAMT increased the mortality risk by six. The acquisition of NI in ICU was also an independent factor of mortality.. EAMT using imipenem-colistin was appropriate in half of the cases and inappropriateness was associated with an increased ICU mortality risk.

Topics: Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Colistin; Critical Illness; Female; Humans; Imipenem; Intensive Care Units; Male; Middle Aged; Prospective Studies; Sepsis

To assess risk factors for recurrent carbapenem-resistant Klebsiella pneumoniae bloodstream-infection (CR-KP BSI), we performed a prospective observational cohort study of all consecutive adult patients cured of a CR-KP BSI at our hospital over a six-year period (June 2010 to June 2016). Maximum follow-up per patient was 180 days from the index blood cultures (BCs). Recurrent CR-KP BSI was defined as new evidence of positive BCs in patients with documented clinical response after completing a course of anti-CR-KP therapy. Univariate and multivariate cause-specific Cox proportional hazards analysis were performed. During the study period 249 patients were diagnosed with a CR-KP BSI, 193 were deemed as cured within 14 days after index BCs and were analysed. Recurrence occurred in 32/193 patients (16.6%) within a median of 35 (IQR 25-45) days after index BCs. All but one of the recurrences occurred within 60 days after the index BCs. Comparison of recurrent and non-recurrent cases showed significant differences for colistin use (84.4% vs. 62.2%, p = 0.01), meropenem-colistin-tigecycline regimen (43.8% vs. 24.8%, p = 0.03) and length of therapy for the index BSI episode (median 18 vs. 14 days, p = 0.004). All-cause 180-day mortality (34.4% vs. 16.1%, p = 0.02) was higher in recurrent cases. In the multivariate analysis, the only independent variable was source control as a protective factor for recurrence. Recurrence is frequent among patients cured of a CR-KP BSI and is associated with higher long-term mortality. When feasible, source control is mandatory to avoid recurrence. The role of antibiotic treatment should be further investigated in large multicentre studies.

Topics: Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Colistin; Cross Infection; Female; Hospitals; Humans; Incidence; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Minocycline; Prospective Studies; Recurrence; Risk Factors; Sepsis; Thienamycins; Tigecycline; Time Factors

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Bacteriophages; Colistin; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Extremely drug-resistant (XDR) Acinetobacter baumannii is one of the most commonly encountered, highly resistant pathogens requiring novel therapeutic interventions.. We developed C8, a monoclonal antibody (mAb), by immunizing mice with sublethal inocula of a hypervirulent XDR clinical isolate.. C8 targets capsular carbohydrate on the bacterial surface, enhancing opsonophagocytosis. Treating with a single dose of C8 as low as 0.5 μg/mouse (0.0167 mg/kg) markedly improved survival in lethal bacteremic sepsis and aspiration pneumonia models of XDR A. baumannii infection. C8 was also synergistic with colistin, substantially improving survival compared to monotherapy. Treatment with C8 significantly reduced blood bacterial density, cytokine production (tumor necrosis factor α, interleukin [IL] 6, IL-1β, and IL-10), and sepsis biomarkers. Serial in vitro passaging of A. baumannii in the presence of C8 did not cause loss of mAb binding to the bacteria, but did result in emergence of less-virulent mutants that were more susceptible to macrophage uptake. Finally, we developed a highly humanized variant of C8 that retains opsonophagocytic activity in murine and human macrophages and rescued mice from lethal infection.. We describe a promising and novel mAb as therapy for lethal, XDR A. baumannii infections, and demonstrate that it synergistically improves outcomes in combination with antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Antibodies, Monoclonal; Biomarkers; Colistin; Cytokines; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; HL-60 Cells; Humans; Macrophages; Male; Mice; Mice, Inbred C3H; Sepsis; Treatment Outcome

Colistin loading dose (LD) has been postulated as an advance in therapy. The clinical, microbiological effectiveness and nephrotoxicity of adding an LD to systemic colistin in ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) Acinetobacter baumannii remain unknown. In this quasi experimental study, the efficacy, outcomes and nephrotoxicity in 30 adults who received intravenous colistin with LD for MDR A. baumannii ventilator associated pneumonia were compared with 22 in absence of LD. Adding LD, the clinical cure rate at 14 days of therapy increased from 47.6% to 56.7% (p>0.397). No significant differences in bacteriological clearance (80 vs 81%), ICU mortality (50% vs 54.2%) or ICU length of stay (median: 32 vs 36 days) were identified. Mortality increased (76.2% vs 35.5%, p=0.004) in patients with nephrotoxicity, with age (median 67.0 vs. 50.0 years, p=0.002) being the only risk factor for nephrotoxicity. The nephrotoxicity rate increased from 27.3% in absence of LD to 35.3% with LD and SOFA <8, and 69.2% (p= 0.065) with LD and SOFA >7. Overall, nephrotoxicity was more severe in the LD group according to RIFLE criteria (p=0.015). Adding LD to systemic colistin for MDR A. baumannii VAP had no significant effect on clinical cure rates, bacteriologic clearance or pre-defined outcomes. However, the nephrotoxicity rate increased with LD, with special risk in adults with high organ failure development or advanced age. Further evidence regarding the risks and benefits of LD is required. The development of newer agents and strategies is urgently needed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Diseases; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Sepsis; Young Adult

Topics: Administration, Intravenous; Colistin; Humans; Infant, Newborn; Neonatal Sepsis; Sepsis

We investigated the efficacy of colistin combined with pexiganan in experimental mouse models of Acinetobacter baumannii infection.Adult male BALB/c mice received intraperitoneally 1 mL saline containing 2 × 10 CFU of susceptible and multiresistant A. baumannii. Two hours after bacterial challenge, animals received 1 mg/kg of colistin, 1 mg/kg of pexiganan, or 1 mg/kg of colistin plus 1 mg/kg of pexiganan.Blood culture positivity, the quantities of bacteria in the intra-abdominal fluid, the rate of lethality and immunological studies, such as immunophenotyping and NK cytotoxicity, were evaluated.In the in vitro study, A. baumannii showed susceptibility to colistin and pexiganan and a strong synergy was observed by testing colistin combined with pexiganan with fractionary inhibitory concentration index of 0.312 for both strains.In the in vivo study colistin or pexiganan alone showed a good antimicrobial efficacy. When colistin was combined with pexiganan, the positive interaction produced low bacterial counts that were statistically significant versus singly treated groups. For both strains the highest rate of survival was observed in combined-treated groups (90%).Pexiganan increased NK cytotoxic activity over the levels of infected and colistin-treated animals.In conclusion, pexiganan combined with colistin was found to be efficacious against A. baumannii infection.

Topics: Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Colistin; Immunophenotyping; Male; Mice; Mice, Inbred BALB C; Sepsis

Neonatal sepsis caused by multidrug-resistant gram-negative bacteria has been reported in different parts of the world. It is a major threat to neonatal care, carrying a high rate of morbidity and mortality. While Colistin is the treatment of choice, few studies have reported its use in neonatal patients.. A retrospective descriptive study of all neonatal patients who had multidrug-resistant Acinetobacter sepsis and were treated with Colistin over a 2-year period. Patients' charts and hospital laboratory data were reviewed.. During the study period, 21 newborns were treated with Colistin. All had sepsis evident by positive blood culture and clinical signs of sepsis. The median gestational age and birth weight were 33 weeks (26-39) and 1700 g (700-3600), respectively. Nine (43 %) were very low birth weight infants. Eighteen (86 %) were preterm infants. Nineteen (91 %) newborns survived. No renal impairment is documented in any of our patients. Fourteen (67 %) of our patients had elevated eosinophil counts following Colistin treatment, for those patients, the average eosinophilic counts ± standard deviation before and after Colistin therapy were 149.08 ± 190.38 to 1193 ± 523.29, respectively, with a p value of less than 0.0001.. Our study showed that Colistin was both effective and safe for treating multidrug-resistant Acinetobacter neonatal sepsis. This is a retrospective study. No universal protocol was used for the patients. The factors that might affect the response or cause side effects are difficult to evaluate.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Sepsis

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

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Daptomycin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Male; Mice, Inbred BALB C; Microbial Sensitivity Tests; Sepsis; Survival Analysis; Teicoplanin; Treatment Outcome

A 50-year-old woman known to have type 1 diabetes mellitus presented with a rare case of angio-oedema associated with colistin use. The angio-oedema was temporally associated with the use and discontinuation of colistin with the reasonable exclusion of important differential diagnoses. Pseudoallergy may be a probable underlying mechanism. However, we cannot exclude the possibility of hereditary angio-oedema type 2 or 3, or that her concomitant medications (particularly enalapril) and her renal impairment contributed to the risk and severity of her angio-oedema.

Topics: Acinetobacter baumannii; Angioedema; Anti-Allergic Agents; Anti-Bacterial Agents; Colistin; Diagnosis, Differential; Female; Humans; Hydrocortisone; Middle Aged; Promethazine; Sepsis; Treatment Outcome; Urinary Tract Infections; Withholding Treatment

Antimicrobial therapy for sepsis caused by carbapenem- and colistin-resistant Klebsiella pneumoniae is not well established. We hypothesized that the early use of gentamicin in cases due to susceptible organisms would decrease the crude mortality rate of this infection.. This retrospective cohort study examined 50 cases of sepsis caused by carbapenem-resistant K. pneumoniae occurring between June 2012 and February 2013 during an outbreak of K. pneumoniae ST512 producing KPC-3, SHV-11 and TEM-1. Survival curves categorized by the use of gentamicin were constructed using the Kaplan-Meier method and compared using the log-rank test. Eight multivariate models using Cox regression were designed to study the risk factors for mortality and test the hypothesis.. The 30 day crude mortality rate was 38%. The use of targeted gentamicin was associated with reduced mortality (20.7% versus 61.9%, P = 0.02). In all multivariate regression models, the use of gentamicin was independently associated with lower mortality until Day 30 (HR 0.17-0.29, P = 0.03-0.002 depending on the model) after controlling for other potential confounding variables such as age, optimal treatment, renal function, severity of infection, underlying disease, use of tigecycline and previous hospitalization.. Gentamicin reduced the mortality from sepsis caused by this K. pneumoniae ST512 clone producing KPC-3, SHV-11 and TEM-1.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Cohort Studies; Colistin; Disease Outbreaks; Drug Resistance, Bacterial; Female; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Retrospective Studies; Risk Factors; Sepsis; Survival Analysis; Treatment Outcome; Young Adult

To observe the safety and efficacy of Colistimethate sodium in children infected with gram-negative bacteria, susceptible only to colistimethate sodium.. This prospective observational study done over 2 years observed children who received colistin for >48 h, for renal failure as defined by p-RIFLE criteria.. Out of 68 children, 52 (76.5%) survived. There were three children with evidence of acute kidney injury and none had neurotoxicity. Serum creatinine significantly decreased at 48 h and at end of treatment, from that at beginning of therapy (P=0.007).. Colistimethate sodium is effective against carbapenem-resistant Gram-negative bacteria, and is safe in children.

Topics: Acute Kidney Injury; Administration, Intravenous; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Creatinine; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Prospective Studies; Sepsis

Acinetobacter baumannii is the most common species to have developed resistance to antibiotics. Due to increasing levels of drug resistance, the available therapeutic options are insufficient in A. baumannii infections. This study investigated the efficacy of doripenem monotherapy versus doripenem combination therapy with sulbactam, amikacin, colistin and tigecycline in experimental sepsis. A carbapenem-resistant A. baumannii was used to develop a sepsis model in 8-10-week-old Balb/c mice by intraperitoneal injection. Antibiotic therapies were initiated two hours after injection of bacterial suspension. Necropsy was performed at 24, 48 and 72 hours and cultures were made from heart, lung, liver and spleen samples. Bacterial loads of lung and liver were calculated as CFU/g. Combination therapies with doripenem were more effective than monotherapy at 24 and 48 hours of infection but no differences between groups were detected at 72 hours. The combination of doripenem with tigecycline and amikacin began to eradicate the bacterial load of lung and liver after 48 hours of infection, whereas doripenem+sulbactam and doripenem+colistin were started to eradication at 72 hours. The results of the study showed that combination therapies with doripenem are more effective than monotherapy and the combination of doripenem with tigeycline or amikacin has more rapid bactericidal effect than that with sulbactam or colistin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Humans; Male; Mice; Mice, Inbred BALB C; Minocycline; Sepsis; Sulbactam; Tigecycline

The prevalence of hospital strains of P. aeruginosa, A. baumannii and K. pneumoniae characterizing by multiple drug resistance to overwhelming majority of antibiotics anew evoked an increased interest to colistin. However, until now there is not enough information concerning pharmacokinetics of colistin to optimize dosage of this pharmaceutical. The study was carried out to analyze pharmacokinetics of both colistin and sodium colistimitate in children with chemically induced neutropenia. To quantitatively detect colistin in blood serum the technique of highly effective fluid chromatography with mass spectrometry was applied. The concentration of colistin was detected in 21 children with chemically induced neutropenia (13 patients with septicemia, 8 children of control group) after intravenous injection of sodium colistimitate. The significant variability of pharmacokinetic parameters of colistin was established both in patients with septicemia and in control group. The technique of highly effective fluid chromatography with mass spectrometry can be applied for therapeutic medicinal monitoring and optimization regimen of dosage.

Topics: Adolescent; Child; Child, Preschool; Colistin; Drug Resistance, Microbial; Female; Humans; Klebsiella pneumoniae; Male; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Topics: Adaptation, Physiological; Aged, 80 and over; Anti-Bacterial Agents; Cholecystitis; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Microbial Sensitivity Tests; Sepsis; Urinary Tract Infections

Critically ill patients with severe sepsis or septic shock may need relatively high colistin daily doses for efficacy against multidrug-resistant and extensively drug-resistant gram-negative rods. However, acute kidney injury (AKI) may represent a major dose-limiting adverse effect of colistin. We sought to determine AKI occurrence and to identify factors influencing AKI risk in severely ill patients receiving colistin according to a recently proposed dosing strategy.. A prospective, observational, cohort study involving patients with severe sepsis or septic shock who received colistin was performed. AKI was defined according to Acute Kidney Injury Network criteria. Colistin administration was driven by a modified pharmacokinetics-pharmacodynamics (PK/PD)-based dosing approach.. Of 70 patients who received colistin at a median daily dose of 9 million IU (MIU; interquartile range, 5.87-11.1 MIU), 31 (44%) developed AKI. In univariate analysis, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA), score and baseline renal impairment were significantly associated with AKI. Moreover, patients with AKI were less frequently treated with adjuvant ascorbic acid (P = .003). In multivariate analysis, independent predictors of AKI were baseline renal impairment (adjusted hazard ratio, 4.15; 95% confidence interval, 1.9-9.2; P < .001) and age (1.03; 1.0-1.05; P = .028), whereas a strong independent renal-protective role emerged for ascorbic acid (0.27; .12-.57; P < .001).. In severely ill patients receiving colistin according to a PK/PD-driven dosing approach, baseline renal impairment and older age strongly predict AKI occurrence, but concomitant administration of ascorbic acid markedly reduces AKI risk, allowing safer use of colistin.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antidotes; Ascorbic Acid; Blighia; Colistin; Critical Illness; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Sepsis; Young Adult

This study compared the effect of monotherapy of colistin, tigecycline, and their combination in sepsis model of mice. OXA-48 producing Carbapenem-resistant Klebsiella pneumoniae (CRKP) strain was used in Balb/c mice. The mice were divided into competent and Methylprednisolone acetate (MPA)-treated groups. Each group was sub-divided into (1) colistin or (2) tigecycline monotherapy and (3) colistin/tigecycline combination therapy. After 3 hours of intraperitoneal bacterial inoculation, antimicrobials were administered, and mice were sacrificed at 24 and 48 hours Time-kill curve study demonstrated that colistin sulphate had early bactericidal activity following re-growth. In competent and MPA-treated groups of mice at 24 hours, bacterial counts in liver samples significantly lowered compared to control, however, there were no statistically differences between monotherapy and combination therapy subgroup. Bacterial count in lung samples of competent group was significantly lesser than control for all three antimicrobial subgroups at 24 hours Colistin plus tigecycline combination therapy was not superior against colistin or tigecycline monotherapy.

Topics: Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Klebsiella pneumoniae; Methylprednisolone; Methylprednisolone Acetate; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Minocycline; Sepsis; Structure-Activity Relationship; Tigecycline

To describe the efficacy of intravenous colistin on clinical and microbiological outcomes in preterm infants with nosocomial sepsis in neonatal intensive care unit (NICU) and define adverse events observed with this treatment.. The records of preterm infants who received colistin with or without positive cultures in the NICU were retrospectively reviewed. Patients were evaluated for response to therapy and side effects.. A total of 21 preterm infants with medians of 28 weeks (23-36) gestational age and 870 g (620-2,650) birth weight were included. The median duration and dose of colistin therapy were 9 days (3-26) and 3 mg/kg/d (2-5). Recovery rate in patients including all with/without positive culture was 81% (17/21). Microbiological clearance by colistin was 69% (9/13). The major side effect observed was acute kidney injury (19%). At least 24% of infants required electrolyte supplementation during the colistin therapy. Magnesium levels were significantly lower at the end of the colistin therapy (p < 0.001). Acute kidney injury and electrolyte disturbances including hypomagnesemia were reversible in all surviving patients.. We suggest that renal function tests and serum electrolytes should be monitored closely and replaced in case of any need during the colistin therapy in preterm infants.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Administration, Intravenous; Anti-Bacterial Agents; Colistin; Cross Infection; Electrolytes; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intensive Care, Neonatal; Magnesium; Male; Microbial Sensitivity Tests; Retrospective Studies; Sepsis; Water-Electrolyte Imbalance

The fitness and virulence costs associated with the clinical acquisition of colistin resistance by Acinetobacter baumannii were evaluated. The growth of strain CR17 (colistin resistant) was less than that of strain CS01 (colistin susceptible) when the strains were grown in competition (72-h competition index, 0.008). In a murine sepsis model, CS01 and CR17 reached spleen concentrations when coinfecting of 9.31 and 6.97 log10 CFU/g, respectively, with an in vivo competition index of 0.016. Moreover, CS01 was more virulent than CR17 with respect to mortality and time to death.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Colony Count, Microbial; Drug Resistance, Bacterial; Female; Genetic Fitness; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Sepsis; Survival Analysis; Virulence

Use of colistin methanesulfonate (CMS) was abandoned in the 1970s because of excessive nephrotoxicity, but it has been reintroduced as a last-resort treatment for extensively drug-resistant infections caused by gram-negative bacteria (Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumonia). We conducted a retrospective cohort study to evaluate risk factors for new-onset acute kidney injury (AKI) in critically ill patients receiving high intravenous doses of colistin methanesulfonate and/or other nephrotoxic antibiotics.. The cohort consisted of 279 adults admitted to two general ICUs in teaching hospitals between 1 April 2009 and 30 June 2011 with 1) no evidence on admission of acute or chronic kidney disease; and 2) treatment for more than seven days with CMS and/or other nephrotoxic antimicrobials (NAs, that is, aminoglycosides, glycopeptides). Logistic regression analysis was used to identify risk factors associated with this outcome.. The 279 cases that met the inclusion criteria included 147 patients treated with CMS, alone (n = 90) or with NAs (n = 57), and 132 treated with NAs alone. The 111 (40%) who developed AKI were significantly older and had significantly higher Simplified Acute Physiology Score II (SAPS II) scores than those who did not develop AKI, but rates of hypertension, diabetes mellitus and congestive heart failure were similar in the two groups. The final logistic regression model showed that in the 147 patients who received CMS alone or with NAs, onset of AKI during the ICU stay was associated with septic shock and with SAPS II scores ≥43. Similar results were obtained in the 222 patients treated with CMS alone or NAs alone.. In severely ill ICU patients without pre-existing renal disease who receive CMS high-dose for more than seven days, CMS therapy does not appear to be a risk factor for this outcome. Instead, the development of AKI was strongly correlated with the presence of septic shock and with the severity of the patients as reflected by the SAPS II score.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Colistin; Critical Illness; Female; Humans; Infusions, Intravenous; Kidney; Male; Middle Aged; Prospective Studies; Retrospective Studies; Risk Factors; Sepsis

Colistin is a decades-old drug that fell out of favour due to its nephrotoxicity. Today, colistin is experiencing a renaissance as a treatment against multiresistant Gram-negative bacteria such as Pseudomonas and Acinetobacter in critically ill patients. The optimal dosing of colistin for most infections is unknown. Here we present the intravenous dosing, optimised by therapeutic drug monitoring (TDM), of a borderline patient with severe burns and a consecutive transfemoral amputation. A 32-year-old woman with severe burns (35% total body surface area) and sepsis exhibited normal serum creatinine (SCr) concentrations at the beginning of her intensive care unit (ICU) stay, but over the course of her ICU stay her SCr increased to 100 μmol/L. With the colistin standard dose of 3 × 3 million units (MU) colistin/day after a loading dose of 9 MU, she failed to achieve effective plasma concentrations. The estimated glomerular filtration rate (eGFR) via CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) revealed GFRs between 180 mL/min and 63 mL/min after correcting for body surface. The patient required a high daily dosage of colistin (3 × 6 MU) that exceeded the approved maximum dose. Most clinicians rely heavily on SCr concentrations as the primary biochemical marker of GFR. At most, the CKD-EPI formula is helpful in determining creatinine clearance. The pharmacokinetics of colistin are currently poorly understood. TDM of colistin methanesulfonate and colistin may represent an invaluable approach to optimise colistin drug exposure in ICU patients with fluctuating renal clearance.

Topics: Administration, Intravenous; Adult; Amputation, Surgical; Anti-Bacterial Agents; Bacterial Infections; Burns; Colistin; Creatinine; Drug Monitoring; Female; Glomerular Filtration Rate; Humans; Sepsis

In recent years, multidrug-resistant Acinetobacter baumannii has been reported as an important nosocomial pathogen, and treatment options are limited. The aim of this study was to investigate the additional effect of sulbactam on monotherapy with colistin, tigecycline and imipenem in experimental sepsis with carbapenem-resistant A. baumannii in mice.. Sepsis was developed in 8- to 10-week-old BALB/c mice by an intraperitoneal injection of A. baumannii. Antibiotic was given intraperitoneally 2 h after bacterial inoculation. Each experimental group had 15 mice and was divided into 3 subgroups. Mice were sacrificed at 24, 48 or 72 h. Lung, liver, heart and spleen samples were cultured, and homogenates of lung and liver were used to detect the number of colony-forming units per gram. Bacterial clearance was compared in lung and liver at different time points.. Imipenem did not decrease the bacterial load, but the other antibiotics showed significant bactericidal activity compared with the control group, and the combination of imipenem with sulbactam decreased the bacterial load in lung and liver. However, the addition of sulbactam to colistin and tigecycline had no significant effect on bacterial counts. Only the addition of sulbactam to imipenem showed better bactericidal activity compared to imipenem alone.. These results suggested that combining sulbactam with tigeycline or colistin does not increase the efficiency of these antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Load; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Imipenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Minocycline; Sepsis; Sulbactam; Tigecycline; Time Factors

Macrophage activation syndrome (MAS) is a systemic disorder with a high mortality, commonly associated with rheumatological conditions, but which can also occur as a complication of several infections. Here we present a case of MAS following Acinetobacter baumannii sepsis. Early institution of therapy with prednisolone, cyclosporine, colistin, and polymyxin resulted in a prompt clinical recovery. There are very few reported cases of Acinetobacter-related MAS that have been successfully treated.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Cyclosporine; Drug Resistance, Multiple, Bacterial; Humans; Macrophage Activation Syndrome; Male; Polymyxins; Prednisolone; Sepsis

Gram-negative bacteria susceptible only to colistin (COS) are emerging causes of severe nosocomial infections, reviving interest in the use of colistin. However, consensus on the most effective way to administer colistin has not yet been reached.. All patients who had sepsis due to COS gram-negative bacteria or minimally susceptible gram-negative bacteria and received intravenous colistimethate sodium (CMS) were prospectively enrolled. The CMS dosing schedule was based on a loading dose of 9 MU and a 9-MU twice-daily fractioned maintenance dose, titrated on renal function. For each CMS course, clinical cure, bacteriological clearance, daily serum creatinine clearance, and estimated creatinine clearance were recorded.. Twenty-eight infectious episodes due to Acinetobacter baumannii (46.4%), Klebsiella pneumoniae (46.4%), and Pseudomonas aeruginosa (7.2%) were analyzed. The main types of infection were bloodstream infection (64.3%) and ventilator-associated pneumonia (35.7%). Clinical cure was observed in 23 cases (82.1%). Acute kidney injury developed during 5 treatment courses (17.8%), did not require renal replacement therapy, and subsided within 10 days from CMS discontinuation. No correlation was found between variation in serum creatinine level (from baseline to peak) and daily and cumulative doses of CMS, and between variation in serum creatinine level (from baseline to peak) and duration of CMS treatment.. Our study shows that in severe infections due to COS gram-negative bacteria, the high-dose, extended-interval CMS regimen has a high efficacy, without significant renal toxicity.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Colistin; Critical Illness; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Kidney Diseases; Male; Middle Aged; Prospective Studies; Sepsis; Treatment Outcome

Topics: Anti-Bacterial Agents; Colistin; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Male; Sepsis

Available data on colistin pharmacokinetics in patients undergoing continuous renal replacement therapy (CRRT) are limited. Our aim was to study colistin pharmacokinetics in critically ill patients treated with colistin methane sulphonate for Gram-negative sepsis and undergoing continuous venovenous haemodiafiltration for acute renal failure.. Three patients were studied. The colistin methane sulphonate dose administered was at the discretion of the attending physician and was in all cases lower than that recommended for individuals with intact renal function. Colistin methane sulphonate was administered intravenously over 30 min, and blood samples were collected from each patient pre- and post-filter for the HPLC determination of colistin levels in serum before infusion, at 10, 60, 120, 240, 360, 480 and 600 min from the end of infusion, and immediately before the next dose. Concurrently, spot samples of effluent from the haemofilter were also collected and analysed. Both colistin total extracorporeal clearance and clearance in the effluent were calculated.. Extracorporeal clearance resulted in substantial removal of colistin (43%-59% of total colistin clearance). Total colistin clearance was found to be reduced (varying between 3.3 and 4.5 L/h), compared with patients with normal renal function. Colistin methane sulphonate dosage resulted in clearly suboptimal colistin steady-state concentrations.. In spite of substantial extracorporeal clearance, total colistin clearance was reduced, compared with patients with normal renal function. Colistin adsorption by the haemofilter contributed to its extracorporeal clearance to a large extent. Studies on other patients receiving colistin methane sulphonate and undergoing CRRT are required before more appropriate dosage regimens can be recommended.

Topics: Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Colistin; Critical Illness; Gram-Negative Bacterial Infections; Hemodiafiltration; Humans; Infusions, Intravenous; Intensive Care Units; Male; Metabolic Clearance Rate; Middle Aged; Sepsis; Serum; Time Factors

Topics: Anti-Bacterial Agents; Colistin; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Male; Sepsis

Acinetobacter baumannii (American Type Culture Collection strain 19606) acquires mutations in the pmrB gene during the in vitro development of resistance to colistin. The colistin-resistant strain has lower affinity for colistin, reduced in vivo fitness (competition index, .016), and decreased virulence, both in terms of mortality (0% lethal dose, 6.9 vs 4.9 log colony-forming units) and survival in a mouse model of peritoneal sepsis. These results may explain the low incidence and dissemination of colistin resistance in A. baumannii in clinical settings.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Female; Mice; Mice, Inbred C57BL; Mutation; Peritonitis; Sepsis; Survival Analysis; Transcription Factors; Virulence

An experimental study was performed to evaluate the interaction between s-thanatin and colistin both in vitro and in vivo, using two Pseudomonas aeruginosa strains with different patterns of susceptibilities. We evaluated whether selecting for colistin-resistant P. aeruginosa could be prevented in vitro by combining colistin with s-thanatin. The strains were serially exposed in broth to twofold stepwise increasing concentrations of colistin alone or in combination with a fixed concentration [0.25× minimum inhibitory concentration (MIC)] of s-thanatin. We also performed an in vitro synergy study. For in vivo studies, a mouse model of Pseudomonas sepsis has been used. Main outcome measures were lethality and quantitative blood cultures. Exposure to colistin alone gradually selected for Pseudomonas strains with an increased MIC. In vitro studies, s-thanatin showed a positive interaction with colistin, and was able to prevent its resistance. In vivo studies, s-thanatin combined with colistin exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of this combination and provide a future therapeutic alternative in severe Pseudomonas infections.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Colistin; Disease Models, Animal; Drug Resistance, Microbial; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of tachyplesin III, colistin, and imipenem against a multiresistant Pseudomonas aeruginosa strain. In vitro experiments included MIC determination, time-kill, and synergy studies. For in vivo studies, a mouse model of sepsis has been used. The main outcome measures were bacterial lethality, quantitative blood cultures, and plasma levels of lipopolysaccharide, tumor necrosis factor alpha, and interleukin-6. The combination of tachyplesin III or colistin with imipenem showed in vitro synergistic interaction. A significant increase in efficacy was also observed in vivo: combination-treated groups had significantly lower levels of bacteremia than did groups treated with a single agent. Tachyplesin III combined with imipenem exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of these combinations and provide therapeutic alternatives for serious infections caused by gram-negative bacteria in the coming years.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Colistin; DNA-Binding Proteins; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Imipenem; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Peptides, Cyclic; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Treatment Outcome

Topics: Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Humans; Pseudomonas Infections; Rats; Rifampin; Sepsis; Treatment Failure

Klebsiella pneumoniae that was resistant to all available antibiotics (minimum inhibitory concentration of imipenem, 32 microg/mL), including carbapenems, was isolated from blood samples obtained from a 48-year-old patient in the intensive care unit. The patient developed septic shock, which was successfully treated with colistin, the only antibiotic with activity against this multidrug-resistant strain.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Sepsis

The efficacy of cationic peptides combined with betalactams was investigated in a peritonitis rat model. Intraabdominal sepsis was induced in adult Wistar rats via cecal ligation and single puncture. The study included eight drug-treated groups: each of them received intravenous polymyxin-E (1 mg/kg), buforin II (1 mg/kg), imipenem (20 mg/kg), amoxicillin-clavulanate (50 mg/kg), polymyxin-E (1 mg/kg) plus imipenem (20 mg/kg), or amoxicillin-clavulanate (50 mg/kg), and buforin II (1 mg/kg) plus imipenem (20 mg/kg), or amoxicillin-clavulanate (50 mg/kg). The study included an untreated control group that received intravenous isotonic sodium chloride solution. All compounds significantly reduced the lethality and the number of bacteria in abdominal fluid compared with saline treatment. Among compounds, imipenem showed the highest antimicrobial activity, while buforin II produced the highest reduction in plasma endotoxin and TNF-alpha levels. Overall, buforin II and imipenem association were the most effective therapeutic approach. Data presented here suggest the potential advantages of combining antimicrobial agents and compounds able to neutralize the biological effect of the endotoxin.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Colistin; Colony Count, Microbial; Disease Models, Animal; Drug Therapy, Combination; Endotoxins; Exudates and Transudates; Imipenem; Male; Peritonitis; Proteins; Rats; Rats, Wistar; Sepsis; Tumor Necrosis Factor-alpha

The first 25 BMTs at the Royal Liverpool Children's Hospital (Alder Hey) were performed between April 1987 and July 1991. The aim of this report is to evaluate selective decontamination of the digestive tract (SDD) during the first post-BMT month in this series of 14 allografts and 11 autografts. SDD is a method used to abolish carriage of potentially pathogenic microorganisms including yeasts, Staphylococcus aureus and Gram-negative bacilli (GNB). Chlorhexidine mouth wash was used to decontaminate the oropharynx, and neomycin, colistin (polymyxin E) and nystatin (NEOCON) were given to eradicate gut carriage. Oropharyngeal decontamination was successful in 48% of patients, gut carriage was abolished in 60%, and eradication of the carrier state at both sites was achieved in 33%. A septic response was seen in 76% of children and 36% developed septicaemia (indigenous Gram-positive cocci only). A low carriage index for the target microorganisms during the study manoeuvre of SDD was associated with negative blood cultures (p < 0.01). Acute GVHD occurred in 28% of allografts, but was seen in none of the successfully decontaminated children (p < 0.05). It is concluded that septicaemia from yeasts and GNB, but not the septic response, were successfully prevented by SDD.

Topics: Adolescent; Bone Marrow Transplantation; Carrier State; Child; Child, Preschool; Chlorhexidine; Colistin; Digestive System; Disease Susceptibility; Drug Therapy, Combination; England; Female; Graft vs Host Disease; Humans; Incidence; Infant; Male; Neomycin; Neutropenia; Nystatin; Premedication; Retrospective Studies; Sepsis; Survival Analysis

Topics: Anti-Bacterial Agents; Colistin; Enterobacteriaceae Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestines; Klebsiella; Sepsis; Serotyping

The chemotherapy of septicaemia in newborns differs fundamentally from that in older children or adults because, although newborns have a fully developed immunological system, the system has not yet "learned" to operate completely. Ultimately, optimal chemotherapy can only be found empirically. In this respect a few basic guidelines can be given however: 1. The initial therapy must bring the pathogen under control with a high degree of certainty, since a correction in therapy following pathogen indentification is usually too late. 2. Since the pharmacokinetics of antibiotics in newborns vary considerably, the minimal peak serum concentration observed should exceed the MIC of the pathogen. 3. In rapidly maturing newborns and premature babies the pharmacokinetics of each antibiotic must be known precisely. 4. Since in the individual case there can never be absolute certainty with respect to the three above-mentioned problems, combination therapy should be given at all times.

Topics: Amikacin; Anti-Bacterial Agents; Cefuroxime; Colistin; Dose-Response Relationship, Drug; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Kinetics; Meningitis; Sepsis; Tobramycin

The effect of antibiotic therapy on the intestinal flora was studied qualitatively and quantitatively in 41 infants. The results have been compared with 27 normal children of the same age and background. Antibiotics were responsible for the suppression of sensitive strains and for their replacement by resistant organisms but above all to a rapid multiplication of the intestinal flora. Colistin and pristinamycin caused these changes when given orally. Ampicillin when given both orally and parenterally but Colistin and the aminoglycosides when given parenterally did not have any effect. Fourteen cases of secondary septicaemia due to resistant organisms were observed but other factors were also important, namely the young age of the patients and intestinal problems (stasis and diarrhoea).

Topics: Age Factors; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Colistin; Feces; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Diseases; Intestines; Klebsiella Infections; Penicillin Resistance; Proteus Infections; Sepsis; Staphylococcal Infections

Of the 108 patients explored, all received four days preoperatively dietary and mechanical preparation and were given one of the two antibiotic combinations according to their date of birth (58 patients, group I--Neomycin-Bacitracin; 50 patients, group II--Cephaloridin-Colistinsulfate). Bacteriologic studies of stools from the day before beginning of preparation, preoperatively and from the day of operation (intestinal mucous membrane of 70 patients) revealed that the fecal flora of the majority of the patients was abnormal. After antibiotic treatment the bacteriologic studies of stools showed a significant reduction of bacteria. In group II, full asepsis was reached in 42.4% of patients, in group I, in only 13.5%. The price of antibiotics and the preoperative intestinal bacteria should be used as criteria in choosing the preparation for colon operations.

Topics: Anti-Bacterial Agents; Bacitracin; Cephaloridine; Colistin; Colon; Enterobacteriaceae; Feces; Female; Humans; Male; Neomycin; Preoperative Care; Sepsis; Surgical Wound Infection

An epidemic caused by Serratia marcescens occurred in intensive care unit of the Children's clinic in Essen, with three deaths. Although there was good sensitivity of the strain to gentamicin in vitro, there was no noticeable clinical improvement when it was administered. But cotrimoxazole, given systemically and locally, and colistin locally cured the disease.

Topics: Colistin; Cross Infection; Disease Outbreaks; Enterobacteriaceae Infections; Gentamicins; Germany, West; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Intensive Care Units; Sepsis; Serratia marcescens; Sulfamethoxazole; Trimethoprim

Topics: Ampicillin; Anti-Bacterial Agents; Carbenicillin; Cefazolin; Cephalothin; Colistin; Drug Therapy, Combination; Gentamicins; Humans; Kanamycin; Polymyxins; Sepsis; Tetracycline

Topics: Aminoglycosides; Anti-Bacterial Agents; Cephalosporins; Colistin; Humans; Kidney; Kidney Function Tests; Penicillins; Polymyxins; Sepsis; Tetracyclines; Urinary Tract Infections

The current circumstances associated with Pseudomonas aeruginosa bacteremia are reviewed in 108 episodes to assess the impact of new antimicrobial drugs on this infection. Since 1961, Pseudomonas bacteremia has apparently become more frequent with proportional increases in middle-aged patients. The respiratory tract has become the major source of infection. Clinical features are not characteristic, but infected patients are almost uniformly severely ill before blood stream invasion occurs. The use of gentamicin, carbenicillin and colistin has not changed the outcome of Pseudomonas bacteremia. Although better than no antimicrobial treatment, these drugs cannot be shown to be superior to any other available antibiotics. A reassessment is needed to evaluate the relationship between the in vitro action and the effectiveness of antibiotics in the treatment of Pseudomonas infection and the use of gentamicin, carbenicillin and colistin in these bacteremias. In view of the poor results with antibiotics, investigation into immunologic prophylaxis and therapy is needed. At the present time, control of the patients' underlying disease contributes most towards assuring survival with Pseudomonas bacteremia.

Topics: Anti-Bacterial Agents; Carbenicillin; Chronic Disease; Colistin; Cross Infection; Gentamicins; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Neoplasms; Penicillin Resistance; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

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: Acute Kidney Injury; Alcuronium; Colistin; Diuresis; Drug Synergism; Female; Humans; Middle Aged; Muscle Spindles; Nerve Block; Neuromuscular Blocking Agents; Sepsis; Time Factors

Topics: Adult; Blood; Carbenicillin; Cephalothin; Colistin; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Gentamicins; Heart Valve Prosthesis; Heroin Dependence; Humans; Male; Mesylates; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Tricuspid Valve

Topics: Birth Weight; Carbenicillin; Catheterization; Cephalothin; Colistin; Gentamicins; Humans; Infant, Newborn; Oxacillin; Sepsis; Time Factors; Umbilical Arteries; Umbilical Veins

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Child; Colistin; Drainage; Female; Gentamicins; Humans; Hypotension; Male; Middle Aged; Peritoneal Dialysis; Postoperative Complications; Renal Dialysis; Sepsis

Topics: Ampicillin; Anti-Bacterial Agents; Carbenicillin; Cephalothin; Chloramphenicol; Colistin; Dicloxacillin; Escherichia coli Infections; Gentamicins; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Streptococcal Infections

Topics: Ampicillin; Bacterial Infections; Carbenicillin; Cephalothin; Child, Preschool; Chloramphenicol; Colistin; Erythromycin; Gentamicins; Humans; Lincomycin; Male; Microbial Sensitivity Tests; Moraxella; Neomycin; Oleandomycin; Oxacillin; Penicillins; Sepsis; Stomatitis; Streptomycin; Sulfamethoxazole; Sulfonamides; Tetracycline; Trimethoprim

Topics: Adult; Aortic Valve; Carbenicillin; Colistin; Corynebacterium diphtheriae; Corynebacterium Infections; Endocarditis, Bacterial; Fascia Lata; Heart Valve Prosthesis; Humans; Male; Penicillin Resistance; Penicillins; Postoperative Complications; Sepsis; Streptomycin

Topics: Ampicillin; Antigens, Bacterial; Cephalothin; Child; Chloramphenicol; Colistin; Escherichia coli; Gentamicins; Humans; Immune Sera; Infant; Kanamycin; Meningitis; Neomycin; Penicillin Resistance; Polymyxins; Sepsis; Serotyping; Streptomycin; Tetracycline; Urinary Tract Infections

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

Topics: Adult; Aged; Agranulocytosis; Bacteria; Carbenicillin; Catheterization; Colistin; Diabetes Complications; Drug Combinations; Endocarditis; Female; Gentamicins; Humans; Leukocytosis; Male; Middle Aged; Plasmacytoma; Pregnancy; Prostatic Hyperplasia; Pseudomonas aeruginosa; Pseudomonas Infections; Puerperal Infection; Sepsis; Stevens-Johnson Syndrome; Uremia

Topics: Acute Kidney Injury; Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Colistin; Deafness; Endocarditis, Bacterial; Female; Humans; Kanamycin; Kidney; Kidney Function Tests; Male; Middle Aged; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Streptococcal Infections; Urea; Vancomycin

Topics: Ampicillin; Cephalothin; Chloramphenicol; Colistin; Cross Infection; Gentamicins; Humans; Kanamycin; Klebsiella Infections; Lung; Penicillin Resistance; Prognosis; Sepsis; Skin; Streptomycin; Sulfonamides; Surgical Wound Infection; Tetracycline; Urinary Tract

Topics: Adolescent; Adult; Age Factors; Aged; Colistin; Cross Infection; Escherichia coli Infections; Female; Fever; Humans; Kanamycin; Klebsiella Infections; Leukocyte Count; Male; Microbial Sensitivity Tests; Middle Aged; Nitrogen; Penicillins; Proteus Infections; Pseudomonas Infections; Retrospective Studies; Sepsis; Sex Factors; Shock; Uremia

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cephaloridine; Chloramphenicol; Colistin; Erythromycin; Escherichia coli; Female; Gentamicins; Humans; Kanamycin; Lincomycin; Male; Meningitis; Microbial Sensitivity Tests; Middle Aged; Novobiocin; Penicillins; Radiography; Respiratory Tract Infections; Sepsis; Staphylococcus; Streptococcus; Streptomycin; Sulfonamides; Tetracycline; Urinary Tract Infections

Topics: Carbenicillin; Colistin; Ecthyma; Gentamicins; Humans; Male; Middle Aged; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Topics: Adolescent; Adult; Aged; Cardiac Output; Cephalothin; Child; Child, Preschool; Colistin; Cross Infection; Female; Hemorrhage; Humans; Immunosuppression Therapy; Kanamycin; Lung; Male; Middle Aged; Neoplasms; Oxygen Consumption; Pancreatitis; Pyelonephritis; Retrospective Studies; Sepsis; Shock, Septic; Thromboembolism

Topics: Abdominal Injuries; Blood Urea Nitrogen; Cardiac Output; Colistin; Creatinine; Humans; Kanamycin; Kidney; Male; Military Medicine; Osmolar Concentration; Penicillins; Sepsis

Topics: Adolescent; Adult; Aged; Chloramphenicol; Colistin; Enterobacteriaceae; Female; Humans; Injections, Intravenous; Kanamycin; Male; Middle Aged; Nalidixic Acid; Nitrofurantoin; Penicillin Resistance; Penicillins; Polymyxins; Sepsis; Urologic Diseases

Topics: Adolescent; Adult; Anti-Bacterial Agents; Benzene Derivatives; Bronchopneumonia; Burns; Child; Child, Preschool; Colistin; Gentamicins; Humans; Infant; Injections, Intravenous; Ointments; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Sulfonamides; Wound Infection

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; Ampicillin; Bacteroides; Bacteroides Infections; Cephalothin; Chloramphenicol; Colistin; Erythromycin; Female; Humans; Kanamycin; Male; Microbial Sensitivity Tests; Middle Aged; Penicillins; Sepsis; Tetracycline

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Colistin; Female; Humans; Infections; Lung Diseases; Male; Middle Aged; Sepsis

Topics: Adult; Burns; Burns, Electric; Candidiasis, Cutaneous; Child; Child, Preschool; Colistin; Escherichia coli Infections; Female; Gentamicins; Humans; Male; Patient Isolators; Penicillins; Polymyxins; Proteus Infections; Pseudomonas Infections; Sepsis; Silver Nitrate; Staphylococcal Infections; Streptococcal Infections; Sulfonamides; Toluene

Topics: Adult; Ampicillin; Colistin; Drug Synergism; Female; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Topics: Amphotericin B; Bronchopneumonia; Candidiasis; Child; Colistin; Female; Humans; Iatrogenic Disease; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infusions, Parenteral; Male; Meningitis; Sepsis; Sterilization; Vaccination

Topics: Animals; Brain; Chloramphenicol; Colistin; Electrocardiography; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Fever; Humans; Infant, Newborn; Infant, Newborn, Diseases; Leukocyte Count; Meningitis; Penicillins; Sepsis; Snakes; Spinal Puncture; Streptomycin; Sulfadiazine

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

Topics: Anti-Bacterial Agents; Child; Chloramphenicol; Colistin; Diazepam; Heparin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Meningitis; Penicillins; Pneumonia, Staphylococcal; Prednisone; Sepsis; Sulfonamides

Topics: Animals; Anti-Bacterial Agents; Burns; Chloramphenicol; Colistin; Gentamicins; In Vitro Techniques; Mice; Neomycin; Polymyxins; Pseudomonas Infections; Sepsis; Streptomycin; Sulfadiazine; Sulfanilamides

Topics: Aged; Catheterization; Chloramphenicol; Clostridium perfringens; Colistin; Dextrans; Enterobacter; Erythromycin; Escherichia coli Infections; Female; Humans; Hydrocortisone; Isoproterenol; Kanamycin; Klebsiella; Male; Methicillin; Middle Aged; Ointments; Penicillins; Sepsis; Staphylococcal Infections; Streptomycin; Strongyloides; Veins

Topics: Adrenal Cortex Hormones; Adult; Ampicillin; Anti-Bacterial Agents; Cephalothin; Chloramphenicol; Colistin; Enterobacter; Enterobacteriaceae; Escherichia coli; Female; Humans; Kanamycin; Klebsiella; Middle Aged; Polymyxins; Proteus; Pseudomonas; Pseudomonas aeruginosa; Sepsis; Shock, Septic; Streptomycin; Tetracycline; Vasoconstrictor Agents

Topics: Acetates; Animals; Anti-Infective Agents, Local; Burns; Colistin; Culture Techniques; Liver; Male; Pseudomonas aeruginosa; Rats; Sepsis; Sulfanilamides

Topics: Adult; Cephalothin; Child; Colistin; Cross Infection; Enterobacter; Enterobacteriaceae Infections; Gentamicins; Germany, West; Humans; Infant, Newborn; Middle Aged; Penicillin Resistance; Penicillins; Postoperative Complications; Sepsis

Topics: Animals; Anti-Bacterial Agents; Burns; Colistin; Immune Sera; Mice; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Wound Infection

Topics: Colistin; Dysentery, Bacillary; Humans; Infant; Male; Sepsis

Topics: Anticoagulants; Colistin; Diagnosis; Drug Therapy; Enterobacter; Escherichia coli Infections; Heparin; Hydrocortisone; Kanamycin; Klebsiella; Mannitol; Proteus Infections; Pseudomonas Infections; Sepsis; Streptomycin; Urinary Tract Infections; Urology; Vasodilator Agents

Topics: Adrenal Cortex Hormones; Bacillus; Colistin; Cross Infection; Drug Therapy; gamma-Globulins; Humans; Lung Diseases; Polymyxins; Postoperative Complications; Pseudomonas aeruginosa; Pseudomonas Infections; Resuscitation; Sepsis

Topics: Anemia; Anemia, Aplastic; Blood Cell Count; Bone Marrow Examination; Colistin; Erythromycin; Female; Humans; Neomycin; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Pseudomonas Infections; Sepsis; Streptomycin; Testosterone; Tetracycline

Topics: Adolescent; Anti-Bacterial Agents; Antibiotic Prophylaxis; Burns; Child; Chloramphenicol; Colistin; Erythromycin; Escherichia coli Infections; gamma-Globulins; Humans; Immune Sera; Infant; Infant, Newborn; Kanamycin; Novobiocin; Polymyxins; Proteus Infections; Pseudomonas Infections; Salmonella Infections; Sepsis; Serum Albumin; Shigella; Sodium Chloride; Solutions; Staphylococcal Infections; Streptococcal Infections; Tetracycline; Vancomycin

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: Anti-Bacterial Agents; Bacteriological Techniques; Cerebrospinal Fluid; Chloramphenicol; Colistin; Coma; Diagnosis; Epidemiology; Erythromycin; Listeria; Listeria monocytogenes; Meningitis; Meningitis, Listeria; Novobiocin; Oleandomycin; Oxytetracycline; Penicillins; Seizures; Sepsis; Serologic Tests; Spiramycin; Sulfonamides; Tetracycline

Topics: Abortion, Septic; Bacteremia; Chloramphenicol; Cholangitis; Colistin; Escherichia coli Infections; Gastroenteritis; Hydrocortisone; Kanamycin; Polymyxins; Prognosis; Sepsis; Shock, Septic; Streptomycin; Urinary Tract Infections

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: Aging; Angiotensins; Bacteremia; Bacteroides; Chloramphenicol; Colistin; Drug Therapy; Enterobacter aerogenes; Escherichia coli Infections; Humans; Iatrogenic Disease; Kanamycin; Metaraminol; Polymyxins; Postoperative Complications; Proteus; Pseudomonas Infections; Sepsis; Sex; Streptomycin; Sympatholytics; Tetracycline; Urinary Tract Infections

Topics: Colistin; Fluid Therapy; Humans; Kidney; Kidneys, Artificial; Pyelonephritis; Renal Dialysis; Sepsis; Serratia marcescens; Streptomycin

Topics: Blood Chemical Analysis; Chemical and Drug Induced Liver Injury; Colistin; Diverticulitis; Diverticulitis, Colonic; Escherichia coli Infections; Hepatitis A; Intestinal Perforation; Kidney Diseases; Pathology; Sepsis; Toxicology

Topics: Agammaglobulinemia; Anti-Bacterial Agents; Chloramphenicol; Colistin; Diagnosis, Differential; Drug Resistance, Microbial; gamma-Globulins; Humans; Infant; Pseudomonas; Pseudomonas Infections; Sepsis

Topics: Candida albicans; Candidiasis; Colistin; Humans; Infections; Klebsiella; Oxytetracycline; Sepsis; Streptomycin

Topics: Acinetobacter; Anti-Bacterial Agents; Cerebrospinal Fluid; Colistin; Humans; Kanamycin; Polymyxins; Sepsis; Streptomycin; Tetracycline