cefamandole and Pseudomonas-Infections

A combination of tobramycin sulfate and cefamandole nafate was used as initial empiric therapy for the treatment of 71 evaluable febrile (temperature greater than 38.5 degrees C) episodes in 64 (neutrophils, less than 1,000/microL) adult patients with cancer and granulocytopenia. Carbenicillin sodium or ticarcillin disodium was substituted for cefamandole in patients with Pseudomonas infections and in patients in whom the initial regimen was unsuccessful. Twenty-nine episodes were randomized to receive tobramycin by continuous infusion, while 42 were randomized to receive tobramycin by interrupted infusion. Twenty-seven (79%) of the 34 documented infections responded to the initial empiric antibiotic combination, ten (83%) of 12 being given continuous infusion and 17 (77%) of 22 being given interrupted infusion of tobramycin. Nephrotoxic reaction occurred in 7% of patients treated with continuous infusion and 15% treated with interrupted infusion, mostly patients older than 60 years. Tobramycin, by either continuous or interrupted infusion, plus cefamandole is safe and efficacious empiric therapy for infections in patients with cancer and granulocytopenia.

Topics: Adult; Aged; Agranulocytosis; Bacterial Infections; Blood Urea Nitrogen; Cefamandole; Clostridium Infections; Creatinine; Drug Administration Schedule; Drug Therapy, Combination; Ear Diseases; Female; Humans; Infusions, Parenteral; Kidney Diseases; Male; Middle Aged; Neoplasms; Pseudomonas Infections; Tobramycin

Ceftizoxime, a new beta-lactamase-resistant, semisynthetic antibiotic, was compared to cefamandole in a prospective randomized trial to determine its efficacy and safety in 21 patients with acute, complicated urinary tract infections. Four patients randomized initially to receive cefamandole were found to have resistant organisms and were treated with ceftizoxime. Dosage for ceftizoxime was 1 gm. administered parenterally every 12 hours, while 1 gm. cefamandole was given every 6 hours. Urine cultures were obtained before the initiation of therapy, on day 4, after completion of therapy and 4 to 6 weeks after therapy. Specified laboratory tests were obtained. Of 14 patients receiving ceftizoxime 11 (79 per cent) and of 7 patients receiving cefamandole 7 (100 per cent) had negative cultures at the completion of therapy and 4 to 6 weeks later. No patient had any adverse reaction to ceftizoxime. Ceftizoxime is a safe and effective antibiotic agent when used as a single agent for complicated urinary tract infections. However, ceftizoxime is much more expensive than cefamandole therapy. Therefore, it is recommended that ceftizoxime be reserved for treatment of urinary tract infections stemming from pathogenic species resistant to the less expensive antimicrobials.

Topics: Adolescent; Adult; Aged; Cefamandole; Cefotaxime; Ceftizoxime; Cephalosporins; Clinical Trials as Topic; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Prospective Studies; Pseudomonas Infections; Random Allocation; Urinary Tract Infections

Pseudomonas luteola (formerly classified as CDC group Ve-1 and named Chryseomonas luteola) is an unusual pathogen implicated in rare but serious infections in humans. A novel beta-lactamase gene, bla(LUT-1), was cloned from the whole-cell DNA of the P. luteola clinical isolate LAM, which had a weak narrow-spectrum beta-lactam-resistant phenotype, and expressed in Escherichia coli. This gene encoded LUT-1, a 296-amino-acid Ambler class A beta-lactamase with a pI of 6 and a theoretical molecular mass of 28.9 kDa. The catalytic efficiency of this enzyme was higher for cephalothin, cefuroxime, and cefotaxime than for penicillins. It was found to be 49% to 59% identical to other Ambler class A beta-lactamases from Burkholderia sp. (PenA to PenL), Ralstonia eutropha (REUT), Citrobacter sedlakii (SED-1), Serratia fonticola (FONA and SFC-1), Klebsiella sp. (KPC and OXY), and CTX-M extended-spectrum beta-lactamases. No gene homologous to the regulatory ampR genes of class A beta-lactamases was found in the vicinity of the bla(LUT-1) gene. The entire bla(LUT-1) coding region was amplified by PCR and sequenced in five other genetically unrelated P. luteola strains (including the P. luteola type strain). A new variant of bla(LUT-1) was found for each strain. These genes (named bla(LUT-2) to bla(LUT-6)) had nucleotide sequences 98.1 to 99.5% identical to that of bla(LUT-1) and differing from this gene by two to four nonsynonymous single nucleotide polymorphisms. The bla(LUT) gene was located on a 700- to 800-kb chromosomal I-CeuI fragment, the precise size of this fragment depending on the P. luteola strain.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; beta-Lactamases; Catheters, Indwelling; Chromosomes, Bacterial; Cloning, Molecular; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Genetic Variation; Isoelectric Focusing; Kinetics; Microbial Sensitivity Tests; Molecular Sequence Data; Phylogeny; Plasmids; Pseudomonas; Pseudomonas Infections; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; Substrate Specificity

Effects of an N-terminal fragment of bactericidal/permeability increasing protein (rBPI21) on bacterial infections were determined. Intravenous (i.v.) rBPI21 increased survival and reduced bacteremia in rats after an iv injection of Escherichia coli O7:K1 bacteria. rBPI21 inhibited the rise in tumor necrosis factor-alpha resulting from challenge with 2 strains of E. coli. Intraperitoneal (ip) injection of rBPI21 increased survival of mice after ip injection of E. coli O7:K1 and Pseudomonas aeruginosa and reduced bacteria in peritoneal lavage fluid and blood and inhibited cytokine production in response to E. coli. rBPI21 alone did not protect mice challenged with E. coli O111:B4 but was protective and reduced bacterial counts when administered in combination with the antibiotic cefamandole. The data show that protection with rBPI21 is associated with reductions in bacterial counts and is enhanced by antibiotics. Bactericidal activity, in addition to antiendotoxin activity, is involved in the efficacy of rBPI21 in models of gram-negative infection.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Blood Proteins; Bronchoalveolar Lavage Fluid; Cefamandole; Colony Count, Microbial; Escherichia coli; Escherichia coli Infections; Interleukin-6; Male; Membrane Proteins; Mice; Mice, Inbred ICR; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Recombinant Proteins; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

The relationships between resistant pathogens, serum levels of gentamicin, and the outcomes of gangrenous or perforated appendicitis were analyzed in 147 patients. Failure to cure the infection occurred significantly more frequently among patients treated with cefoperazone or cefamandole than among those treated with clindamycin and gentamicin in combination. The failures were associated with recovery of resistant Bacteroides fragilis from intraoperative cultures. Pseudomonas species were also associated with failures, their in vitro susceptibility not correlating with clinical cure. Patients with gentamicin peak serum levels of less than 6 micrograms/ml in the first three days were not more likely to be associated with failure than were patients with higher levels. These clinical observations indicate that antibiotic therapy of intra-abdominal sepsis should include antibiotics with in vitro activity against B fragilis and that precise adjustments of gentamicin levels may not improve outcome. In addition, Pseudomonas species may play a significant role in some of these infections.

Topics: Anti-Bacterial Agents; Appendicitis; Bacteroides fragilis; Bacteroides Infections; Cefamandole; Cefoperazone; Cephalosporins; Clindamycin; Drug Therapy, Combination; Female; Gangrene; Gentamicins; Humans; Male; Pseudomonas; Pseudomonas Infections; Rupture, Spontaneous

The safety and efficacy of treatment with cefamandole were evaluated in 30 patients (from 18 institutions) with serious bone and joint infections. Five of the subjects were children. The antibiotic was given intramuscularly or intravenously in doses ranging from 2 to 12 g daily for five to 44 days. Twenty-six of the 30 patients responded satisfactorily. Fourteen of the fifteen infections due to Staphylococcus aureus were among the successful cases. Other pathogens were streptococci, Escherichia coli, Proteus mirabilis, and Bacteroides fragilis. The drug was well tolerated in patients in this series. Studies indicated that cefamandole penetrated the bones and joints. Further investigation of cefmandole in the treatment of bone and joint infections is warranted.

Topics: Adolescent; Adult; Aged; Arthritis, Infectious; Bacterial Infections; Bacteroides Infections; Bursitis; Cefamandole; Cephalosporins; Child; Child, Preschool; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Osteomyelitis; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Surgical Wound Infection