colistin and Peritonitis

Alternative treatments are needed against NDM-1-producing Escherichia coli. Colistin (COL) and fosfomycin (FOS) often remain active in vitro but selection of resistant mutants is frequent if used separately. We determined whether the combination of colistin and fosfomycin may be useful to treat infections with NDM-1-producing E. coli with varying levels of resistance.. Isogenic derivatives of E. coli CFT073 with blaNDM-1 and variable levels of resistance to colistin and fosfomycin (CFT073-NDM1, CFT073-NDM1-COL and CFT073-NDM1-FOS, respectively) were used. The combination (colistin + fosfomycin) was tested in vitro and in a fatal peritonitis murine model. Mortality and bacterial loads were determined and resistant mutants detected.. Colistin MICs were 0.5, 16 and 0.5 mg/L and fosfomycin MICs were 1, 1 and 32 mg/L against CFT073-NDM1, CFT073-NDM1-COL and CFT073-NDM1-FOS, respectively. In time-kill curves, combining colistin with fosfomycin was synergistic and bactericidal against CFT073-NDM1 and CFT073-NDM1-FOS, with concentrations of 4× MIC (for both drugs), but not against CFT073-NDM1-COL (concentrations of colistin = 0.5× MIC), due to regrowth with fosfomycin-resistant mutants. Mice died less and bacterial counts were lower in spleen with the combination compared with monotherapy against all strains; the combination prevented selection of resistant mutants except for CFT073-NDM1-COL where fosfomycin-resistant mutants were found in all mice.. Combining colistin and fosfomycin was beneficial in vitro and in vivo against NDM-1-producing E. coli, even with strains less susceptible to colistin and fosfomycin. However, the combination failed to prevent the emergence of fosfomycin-resistant mutants against colistin-resistant strains. Combining colistin and fosfomycin constitutes an alternative for treatment of NDM-1 E. coli, except against colistin-resistant strains.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Colistin; Disease Models, Animal; Drug Synergism; Escherichia coli; Fosfomycin; Mice; Microbial Sensitivity Tests; Peritonitis

Multidrug-resistant organisms cause significant morbidity and mortality. Infections due to resistant gram-negative bacilli are increasingly being reported. For years, carbapenem antibiotics have been successfully used to treat infections due to resistant Enterobacteriaceae, such as

Topics: Aged, 80 and over; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Colistin; Enterobacteriaceae Infections; Female; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Peritonitis

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

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

Topics: Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Genotype; Humans; Male; Microbial Sensitivity Tests; Molecular Typing; Peritonitis; Sequence Analysis, DNA

Topics: Abdominal Injuries; Coinfection; Colistin; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Intestinal Perforation; Intestine, Small; Male; Middle Aged; Peritonitis; Phylogeny; Pneumoperitoneum; Ribotyping; RNA, Bacterial; RNA, Ribosomal, 16S; Sequence Alignment; Sequence Homology, Nucleic Acid; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Wounds, Nonpenetrating

Immunocompromised patients, such as those with multiple myeloma on peritoneal dialysis, are particularly susceptible to the occurrence of peritonitis.. We presented a 56-year-old female patient with a 10-year history of multiple myeloma. The patient was on peritoneal dialysis since 2010. During 2012 the patient had the first episode of peritonitis that was successfully managed, but in 2013 the second episode of peritonitis occured. Analysis of dialysate culture and exit site swab revealed the presence of multiresistant Acinetobacter spp., which was susceptible only to colistin. Prompt colistin therapy was administered at the doses of 100,000 units/day during six days, which resulted in complete recovery of the patient, as well as improvement of local abdominal findings. Gram-negative bacteria (genus Acinetobacter) are common causative agents in hospital-acquired infections. Studies confirmed susceptibility of Acinetobacter to colistin, which was also the case with the presented patient. Intravenous administration of colistin resulted in a complete remission of this severe, life-threatening peritonitis.. Patients with multiple myeloma and renal failure are highly prone to severe life-threatening infections.

Topics: Acinetobacter; Anti-Bacterial Agents; Colistin; Cross Infection; Female; Humans; Immunocompromised Host; Kidney Failure, Chronic; Middle Aged; Multiple Myeloma; Peritoneal Dialysis; Peritonitis; Treatment Outcome

A carbapenem-resistant Acinetobacter baumannii strain was isolated from the peritoneal fluid of a patient with complicated intra-abdominal infection and evaluated at the Multidrug-resistant Organism Repository and Surveillance Network by whole-genome sequencing and real-time PCR. The isolate was sequence type 25 and susceptible to colistin and minocycline, with low MICs of tigecycline. blaNDM-1 was located on a plasmid with >99% homology to pNDM-BJ02. The isolate carried numerous other antibiotic resistance genes, including the 16S methylase gene, armA.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; High-Throughput Nucleotide Sequencing; Honduras; Humans; Male; Methyltransferases; Minocycline; Peritonitis; Plasmids; Tigecycline

Topics: Aged, 80 and over; Anti-Bacterial Agents; Ascitic Fluid; Colistin; Humans; Male; Peritonitis

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

Nosocomial infections due to MDR P. aeruginosa are an increasing problem. Therapeutical options are few. We describe two haematological patients with severe neutropenia and systemic infection due to MDR P. aeruginosa treated successfully with colistin plus ceftazidime. Severe adverse events were not described.

Topics: Acute Disease; Adrenal Cortex Hormones; Aged; Anemia, Refractory, with Excess of Blasts; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Ceftazidime; Colistin; Colitis; Disease Susceptibility; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Infusions, Intravenous; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasms, Second Primary; Peritonitis; Postoperative Complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pseudomonas Infections; Radiation Injuries; Spinal Neoplasms; Typhlitis

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

This study was undertaken to find out whether translocation of bacteria to the abdominal cavity and endotoxemia in rats with sterile peritonitis could be prevented by selective decontamination of the digestive tract. Sterile peritonitis was caused by the intraperitoneal injection of either 100, 150, 200, or 300 mg of zymosan suspended in paraffin.. The frequency of infection of the abdominal cavity depended on the dose of zymosan given, ranging from 20% in rats receiving 100 mg to 89% in rats receiving 300 mg of zymosan. In rats not receiving antibiotics for selective decontamination of the digestive tract (the control group). Gram-negative bacilli were isolated from the digestive tract in all rats, and Gram-negative bacilli were isolated from the abdominal cavity in ten of 19 rats. In rats receiving antibiotics for selective decontamination of the digestive tract, Gram-negative bacilli were isolated from the digestive tract in none of the 14 rats, and likewise, Gram-negative bacilli were isolated from the abdominal cavity in none of the 14 rats (p < .005). Moreover, in rats receiving antibiotics for selective decontamination of the digestive tract, endotoxin levels in feces and plasma were significantly lower, as compared with rats not receiving antibiotics for selective decontamination of the digestive tract.. Selective decontamination of the digestive tract prevents translocation of Gram-negative bacilli to the abdominal cavity, and endotoxemia and mortality in rats with sterile peritonitis.

Topics: Animals; Anti-Bacterial Agents; Colistin; Digestive System; Endotoxins; Feces; Gram-Negative Bacteria; Gram-Positive Bacteria; Peritonitis; Rats; Tobramycin; Zymosan

Edwardsiella tarda is an uncommon enteric bacterium which has been found generally in animal hosts and occasionally in human feces. Three cases of extraintestinal infection caused by E. tarda which are described herein include a typhoid-like illness, peritonitis with sepsis, and cellulitis from a wound acquired while fishing. The microbiology of E. tarda and the previous reports of infection due to this organism are reviewed.

Topics: Adult; Cellulitis; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Male; Middle Aged; Peritonitis

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Burns; Cephalothin; Colistin; Drug Therapy, Combination; Gentamicins; Humans; Male; Middle Aged; Peritonitis; Postoperative Complications; Pseudomonas Infections

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Cephaloridine; Chloramphenicol; Colistin; Humans; Injections, Intraperitoneal; Kanamycin; Mice; Microbial Sensitivity Tests; Penicillin G; Peritonitis; Streptomycin; Tetracycline

Topics: Anti-Bacterial Agents; Colistin; Humans; Infection Control; Intestine, Large; Microbial Sensitivity Tests; Neomycin; Peritoneal Cavity; Peritonitis; Postoperative Complications; Procaine; Rectum; Tyrothricin

Topics: Abdomen, Acute; Appendicitis; Colistin; Drug Synergism; Exudates and Transudates; Humans; Intestines; Penicillins; Peritonitis; Postoperative Care

Topics: Abnormalities, Multiple; Blood Glucose; Calcium; Colistin; Female; Hernia, Umbilical; Humans; Hydrocortisone; Hypoglycemia; Infant, Newborn; Peritonitis; Pregnancy; Tongue

Topics: Animals; Anti-Bacterial Agents; Blood Pressure; Blood Proteins; Chloramphenicol; Colistin; Dogs; Erythromycin; Feces; Gastric Juice; Hematocrit; Hydrogen-Ion Concentration; Injections, Intraperitoneal; Injections, Intravenous; Kanamycin; Mice; Penicillins; Peritonitis; Streptomycin; Tetracycline

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: Abdomen; Abdomen, Acute; Abdominal Cavity; Anti-Bacterial Agents; Biomedical Research; Colistin; Dogs; Intestines; Oxytetracycline; Peritonitis; Rabbits; Research; Streptomycin; Surgical Procedures, Operative

Topics: Acute Disease; Anti-Bacterial Agents; Appendicitis; Child; Colistin; Humans; Infant; Peritonitis; Urinary Tract