colistin and Shock--Septic

Endotoxin is a potent stimulator of the inflammatory response and is believed to initiate the pathology in gram-negative sepsis. Agents are being searched for that bind and neutralize or block the effects of endotoxin. The aim was to study the anti-endotoxic effects of polymyxin-E (colistin) in endotoxaemic dogs. The study included a total of 30 endotoxaemic dogs, which were divided into two groups (control = 15; test = 15) of both sexes, different breeds and ages. Hetastarch colloid solution (Expahes,10 mL/kg, i.v.) with lactated Ringer's solution (20 mL/kg, i.v., Q12 h) was given to all dogs. While ampicillin was administered (Alfasilin, 10 mg/kg, i.m., Q12 h) as an antibacterial to the control group, colistin (12,500 IU/kg, i.m., Q12 h) + ampicillin were administered to the test group. The clinical examination (body temperature, pulse and respiration rates, capillary filling times, peripheral pulse qualities, dehydration degrees), hematological and biochemical examinations (WBC, RBC, HGB, HCT, thrombocyte, serum urea, creatinine and TNF-alpha) were performed both before the treatment, and 2, 4, 12 and 24 h after the treatment. In comparison with the control group, it was observed that test group had shorter capillary filling time at 24 h (P < 0.001). Moreover, the degree of dehydration in test group, was significantly improved at 24 h (P < 0.01). While the differences in peripheral pulse qualities significantly differed between 0 and 2 h in controls, at 2, 4, 24 h after treatment it was found to be significantly increased when compared with 0 h in the test group. Serum TNF-alpha concentrations were statistically decreased in the test group between 0 h and other times (P < 0.01). When compared with controls, serum TNF-alpha concentrations were lower at 2, 4, 12 and 24 h in test group (P < 0.05). Results of the study indicated that polymyxin-E (colistin) has an anti-endotoxic effect and is safe for the dogs with endotoxemia at the dosage used in this study.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Blood Chemical Analysis; Colistin; Dog Diseases; Dogs; Double-Blind Method; Drug Combinations; Female; Injections, Intramuscular; Male; Shock, Septic; Treatment Outcome; Tumor Necrosis Factor-alpha

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

Colistin is considered as the last-line antibiotic for the treatment of infections caused by extensively drug-resistant Gram-negative pathogens belonging to the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) group. The present study aimed to explore the colistin resistance mechanisms of a Klebsiella aerogenes (formerly Enterobacter aerogenes) isolate (Kae1177-1bg) obtained from a Bulgarian critically ill patient with septic shock in 2020. Antimicrobial susceptibility testing and whole-genome sequencing using DNA nanoball technology were performed. The resulting read pairs were used for draft genome assembly, MLST analysis and mutation screening in the pmrA/B, phoP/Q, and mgrB genes. Kae1177-1bg demonstrated high-level resistance to colistin, resistance to 3rd generation cephalosporins and susceptibility to all other antibiotics tested. In our strain a CMY-2-type class C cephalosporinase was the only β-lactamase identified. No mobile colistin resistance (mcr) genes were detected. A total of three missense variants in the genes for the two-component PmrA/PmrB system were identified. Two of them were located in the pmrB (pR57K and pN275K) and one in the pmrA gene (pL162M). The pN275K variant emerged as the most likely cause for colistin resistance because it affected a highly conservative position and was the only nonconservative amino acid substitution. In conclusion, to the best of our knowledge, this is the first documented clinical case of a high-level colistin-resistant K. aerogenes in Bulgaria and the first identification of the nonconservative amino acid substitution pN275K worldwide. Colistin-resistant Gram-negative pathogens of ESKAPE group are serious threat to public health and should be subjected to infection control stewardship practices.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bulgaria; Colistin; Critical Illness; Drug Resistance, Bacterial; Enterobacter aerogenes; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Shock, Septic

This study aimed to assess the effectiveness of trimethoprim-sulfamethoxazole (TMP/SMX) as monotherapy for the treatment of carbapenem-resistant Acinobacter baumannii (A. baumannii) (CRAB) infections.. This retrospective cohort study included patients receiving TMP/SMX as the main treatment for severe infections caused by CRAB, who were matched with patients treated with colistin or ampicillin-sulbactam (AMP/SUL) by age, Charlson score, department, and source of infection. Outcomes were compared among all patients and in a subgroup of propensity-score (PS) matched patients. The PS matching was performed using a match tolerance of 0.15 with replacement.. Fifty-three patients treated with TMP/SMX and 83 matched patients treated with colistin or AMP/SUL were included. Variables that were independently significantly associated with TMP/SMX treatment included admission for infection and septic shock, while abnormal cognition on admission and intensive care unit admission were associated with colistin or AMP/SUL treatment. All-cause 30-day mortality was lower with TMP/SMX compared with the comparator antibiotics among all patients (24.5%, 13 of 53 vs. 38.6%, 32 of 83, P=0.09) and in the PS-matched subgroup (29%, 9 of 31 vs. 55.2% 16 of 29, P=0.04). Treatment failure rates were not significantly different overall (34%, 18 of 53 vs. 42.4%, 35 of 83, P=0.339) and in the PS-matched subgroup (35.5%, 11 of 31 vs. 44.8%, 13 of 29, P=0.46). Time to clinical stability and hospitalization duration were significantly shorter with TMP/SMX. Patients treated with TMP/SMX probably had less severe infections than those treated with other antibiotics, even after matching.. TMP/SMX might be a valuable treatment option for TMP/SMX-susceptible CRAB infections. Given the very limited available treatment options, further studies assessing its effectiveness and safety are necessary.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Ampicillin; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Retrospective Studies; Shock, Septic; Sulbactam; Trimethoprim, Sulfamethoxazole Drug Combination

A significant cause of mortality in the intensive care unit (ICU) is multidrug-resistant (MDR) Gram-negative bacteria, such as MDR

Topics: Acinetobacter baumannii; Aged; Bacterial Proteins; beta-Lactamases; Colistin; Critical Care; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Retrospective Studies; Shock, Septic

Topics: Anti-Bacterial Agents; Ciprofloxacin; Colistin; Cupriavidus; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Middle Aged; Shock, Septic; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Child; Child, Preschool; Colistin; Diabetes Complications; Diabetes Mellitus; Drug Resistance, Bacterial; Female; Hospitalization; Humans; Infant; Infant, Newborn; Intensive Care Units; Lebanon; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Mortality; Prevalence; Respiration, Artificial; Retrospective Studies; Risk Factors; Shock, Septic; Steroids; Tigecycline; Treatment Outcome; Young Adult

Despite of proven LPS neutralizing activity, intravenous polymyxin use was waned due to experience of associated nephrotoxicity. But, increasing resistance to all available antibiotics has necessitated their resurgence and the prodrug of colistin sulfate (CS), known as colistin-methanesulfonate (CMS), is increasingly used as the only therapeutic option in many infections. Currently available CMS employ very different dose definitions and thus because of complex pharmacokinetics/pharmacodynamics information and short half-life, this drug use remains confusing. We aimed to expose CS in endotoxic shock models by micro-osmotic pump and evaluated its effectiveness.. We used micro-osmotic pumps to deliver either sterile saline or CS at different dosages ranging from 0.25mg/day to 7mg/day for consecutive 3days in LPS (8mg/kg body weight) induced endotoxic mice and observed their outcome twice daily for a week to determine the survival rate. Serum pro-inflammatory cytokine levels and apoptosis in renal tissues in these models were evaluated.. We showed endotoxic shock was reversed and all mice survived with a CS administration at a dosage of 2mg/day for 3 days, in comparison to survival rate with saline administration (p≤0.0001) in endotoxic models. CS infusion in shock models using micro-osmotic pump ameliorated rising of serum TNF-α, IL-12p70 and IL-6 levels. Nephrotoxicity was evident only with a higher dosage, but not with a lower dosage which was optimum to control endotoxic shock in models.. These results highlighted that an optimal dosage of CS effectively improved outcome in endotoxic shock models without causing nephrotoxicity when administered at a slow and sustained manner. And a higher CS dosage administration was nephrotoxic and fatal. Thus this study bought an opportunity to consider future investigations with CS administration in murine Gram-negative bacterial infections in a novel way.

Topics: Animals; Apoptosis; Colistin; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Endotoxins; Gram-Negative Bacterial Infections; Kidney; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Necrosis; Polymyxins; Shock, Septic; Survival Rate

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

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

Colistin pharmacokinetics data are scarce regarding patients undergoing renal replacement therapy (RRT), or even absent as in patients treated with sorbent technologies potentially capable of removing colistin by extensive absorption on many polymeric materials.. Twelve septic shock patients with acute kidney injury (AKI) undergoing RRT [continuous venovenous hemodiafiltration (CVVHDF) n = 7, coupled-plasma filtration adsorption-HF (CPFA-HF) n = 4, hemoperfusion n = 1] treated with colistin methanesulfonate at a dose of 4.5 × 10(6) U bid were studied. Colistin A (Col-A) and colistin B (Col-B) concentrations on plasma and effluent at time 0, 0.2, 1, 3, 6, 12, 24 and 48 h were determined by the liquid chromatography-tandem mass spectrometry method.. With CVVHDF the sieving coefficient was lower for Col-A, peaked early (0.40 for Col-A at 10 min, and 0.59 for Col-B at 3 h) and declined after 48 h (0.22 and 0.30 for Col-A and Col-B, respectively). Colistin's filter clearance showed a similar pattern, with the highest clearance value of 18.7 ml/min for Col-B at 1 h. With CPFA-HF after the cartridge the Col-A and Col-B levels were negligible (<0.2 mg/l) or not detectable. The sum of the effluent and cartridge clearances reached values of 30 and 40 ml/min for Col-A and Col-B, respectively. With hemoperfusion the postcartridge concentrations for Col-A and Col-B were about 30 % lower than those determined precartridge.. During CPFA-HF and CVVHDF, the extent of colistin removal is high, and patients should receive an unreduced dosage. However, due to risk of accumulation in long-term administration colistin plasma levels determination is recommended.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Chromatography, Liquid; Colistin; Critical Illness; Female; Follow-Up Studies; Hemodiafiltration; Humans; Male; Mass Spectrometry; Middle Aged; Shock, Septic; Sorption Detoxification

Topics: Adult; Anti-Bacterial Agents; Coinfection; Colistin; Combined Modality Therapy; Disease Susceptibility; Drug Substitution; Drug Therapy, Combination; Humans; Kidney Failure, Chronic; Male; Muscle Hypotonia; Osteomyelitis; Renal Dialysis; Reoperation; Respiration, Artificial; Respiratory Insufficiency; Shock, Septic; Spinal Dysraphism; Surgical Wound Infection

Lipopolysaccharide (LPS) is a major contributing factor to endotoxic shock. Colistin specifically binds to LPS. However, it has the disadvantages that adverse reactions are common and it has a short half-life. To overcome these disadvantages, we prepared slow-releasing colistin microspheres and examined the efficacy of these colistin microspheres in a mouse model of endotoxin-induced sepsis. We prepared the colistin microspheres using poly-lactic-co-glycolic acid. For acute toxicity investigations, mice were overdosed with colistin sulfate or colistin microspheres. The group administered with colistin microspheres was associated with less acute toxicity and fewer nephrotoxic changes on histopathological examination compared to the group administered with colistin sulfate alone. For pharmacokinetic analysis, mice were subcutaneously administered with colistin microspheres or colistin sulfate alone. The plasma concentration of colistin was higher in the colistin microspheres group than in the colistin sulfate group at 12 and 24 h after administration. Moreover, mice were intraperitoneally injected with LPS and then immediately subcutaneously administered with blank microspheres, colistin microspheres or colistin sulfate alone. The levels of endotoxin in the sera and cytokine in the spleens were then measured. A significant reduction in the serum endotoxin level in the colistin microspheres group was observed at 24 h. The reduced endotoxin levels in the sera were correlated with the lower cytokine levels in the spleens of mice treated with colistin microspheres. Our results suggest that the use of colistin microspheres may help to maintain a higher colistin concentration in blood, reduce the levels of endotoxin and cytokines in endotoxin-induced sepsis, and lead to decreased toxicity.

Topics: Animals; Anti-Bacterial Agents; Colistin; Delayed-Action Preparations; Disease Models, Animal; Endotoxins; Injections, Subcutaneous; Kidney; Lipopolysaccharides; Male; Mice; Mice, Inbred C3H; Microspheres; Shock, Septic

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Amikacin; Brain Ischemia; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Fatal Outcome; Humans; Hydrocephalus; Injections, Spinal; Male; Meningitis, Bacterial; Pseudomonas Infections; Shock, Septic; Surgical Wound Infection; Ventriculostomy

To investigate the efficacy of rifampin and colistin in three experimental rat models of Pseudomonas aeruginosa sepsis.. Prospective, randomized, controlled animal study.. Research laboratory in a university hospital.. Adult male Wistar rats.. Adult male Wistar rats were given a) an intraperitoneal injection of 1 mg of P. aeruginosa 10 lipopolysaccharide; b) 2 x 10(10) colony-forming units of P. aeruginosa ATCC 27853; and c) 2 x 10(10) colony-forming units of one clinically multiresistant strain of P. aeruginosa. For each model, all animals were randomized to receive intravenously isotonic sodium chloride solution, 10 mg/kg rifampin, 1 mg/kg colistin, and 10 mg/kg rifampin plus 1 mg/kg colistin.. Lethality, bacterial growth in blood and peritoneum, and endotoxin and tumor necrosis factor-alpha concentrations in plasma were measured. Colistin exerted a strong antimicrobial activity and achieved a significant reduction of plasma endotoxin and tumor necrosis factor-alpha concentration compared with control and rifampin-treated groups. Rifampin exhibited no antimicrobial activity with no substantial impact on endotoxin and tumor necrosis factor-alpha plasma concentrations. The combination of colistin and rifampin resulted in a significant reduction in bacterial count compared with colistin monotherapy, whereas no significant difference was found in positive hem cultures and mortality rates between the two groups.. Colistin and rifampin might have a role in the therapy of multiresistant P. aeruginosa infection.

Topics: Animals; Anti-Bacterial Agents; Cells, Cultured; Colistin; Colony Count, Microbial; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Male; Microbial Sensitivity Tests; Prospective Studies; Pseudomonas Infections; Random Allocation; Rats; Rats, Wistar; Rifampin; Shock, Septic; Survival Analysis

Reported here is the case of a patient with septic shock due to multidrug-resistant Acinetobacter baumannii, which developed after complicated acute pancreatitis with intra-abdominal abscess. Treatment with colistin methanesulphonate and high doses of meropenem were initiated, but since shock persisted, tigecycline was added to the regimen, resulting in successful resolution of the infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Meropenem; Minocycline; Pancreatitis, Acute Necrotizing; Shock, Septic; Thienamycins; Tigecycline; Treatment Outcome

An animal study was performed to investigate the efficacy of two glycopeptides and two cationic peptides in the prevention of lethality in a septic shock rat model. Adult Wistar rats were given an intraperitoneal injection of 2x10(10) CFU of Escherichia coli ATCC 25922, with the exception of an uninfected control group (C0). Animals were randomized to receive, immediately after bacterial challenge, intraperitoneally isotonic sodium chloride solution (control group C1), 3 mg/Kg teicoplanin (group 1), 7 mg/Kg vancomycin (group 2), 1 mg/Kg colistin (group 3), 1 mg/Kg buforin II (group 4), or 60 mg/Kg piperacillin (group C(PIP)). In addition, four groups (1a, 2a, 3a, and 4a) received the above mentioned drugs in combination with piperacillin. All compounds and combinations significantly reduced the lethality and the number of E. coli in abdominal fluid compared with C1 group, with the exception of the glycopeptides. Colistin and buforin II combined with piperacillin significantly decreased the lethality compared with piperacillin alone. Finally, colistin, buforin II, and teicoplanin significantly reduced plasma endotoxin concentration in comparison with piperacillin and saline treatment. Antimicrobial peptides and teicoplanin act as antiendotoxin agents and enhance the efficacy of piperacillin.

Topics: Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Injections, Intraperitoneal; Male; Penicillins; Piperacillin; Proteins; Random Allocation; Rats; Rats, Wistar; Shock, Septic; Teicoplanin; Vancomycin

Pretreatment with multiple doses of polymyxin B and colistimethate was evaluated as to its ability to sequester sufficient antibiotic in tissues to neutralize the effects of endotoxin in three animal models. Animals were challenged with endotoxin 24, 48, or 72 h after the last dose of antibiotic when there was minimal or not detectable drug in serum. Pretreatment with polymyxin B was successful in preventing the generalized Shwartzman reaction in rabbits and reducing endotoxin lethality in mice; however, large doses (20 mg per kg per day for 2 or 4 days) were required. Prolongation by more than 24 h of the interval between the last dose of polymyxin B and endotoxin challenge resulted in reduction or loss of protection. Dogs were unable to tolerate the high polymyxin B dosage which was protective in the mouse and rabbit. Lower, nontoxic doses of polymyxin B in dogs did not prevent endotoxin shock and lethality, even when challenged as soon as 1 h after the last dose. Pretreatment with colistimethate was ineffective in all three animal models.

Topics: Animals; Colistin; Dogs; Drug Antagonism; Endotoxins; Escherichia coli; Kidney; Kidney Cortex Necrosis; Lethal Dose 50; Lipopolysaccharides; Liver; Mice; Muscles; Polymyxins; Polysaccharides, Bacterial; Premedication; Rabbits; Shock, Septic; Shwartzman Phenomenon

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: Adult; Amphotericin B; Colistin; Diagnosis, Differential; Endocarditis, Subacute Bacterial; Humans; Hydrocortisone; Infusions, Parenteral; Injections, Intravenous; Male; Mycoses; Penicillins; Shock, Septic; Streptomycin

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

Topics: Colistin; Drug Hypersensitivity; Otitis Media; Prednisolone; Shock; Shock, Septic; Therapeutic Irrigation; Toxicology