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PubMedDate not supplied

The polymicrobial etiology of acute pelvic inflammatory disease and treatment regimens.

Continued research on acute pelvic inflammatory disease (PID) has demonstrated that PID has a rather remarkably varied etiology, the pathogens responsible including Neisseria gonorrhoeae, Chlamydia trachomatis, aerobic and anaerobic gram-positive and gram-negative organisms, and possibly mycoplasmas. There is clearly no single antimicrobial agent that is effective against all of the organisms implicated in the etiology of acute PID. The aminoglycosides, generally in combination with an antibiotic such as clindamycin, are commonly used in the treatment of patients with acute PID. The combination of a new monocyclic beta-lactam antibiotic, aztreonam, and clindamycin may be less toxic and equally or more effective for the treatment of acute PID.

Anti-Bacterial Agents↗
PubMedDate not supplied

Infections due to gram-negative bacteria: an overview.

Infections caused by gram-negative bacteria have continued to be a major problem for hospitalized patients. Malignant necrotizing otitis due to Pseudomonas aeruginosa has been encountered with increasing frequency as the number of older diabetic patients has increased. Nosocomial sinusitis and bacteremia due to Escherichia coli, Klebsiella pneumoniae, Enterobacter species, or P. aeruginosa develop in hospitalized patients. Bacteremia due to E. coli, K. pneumoniae, or P. aeruginosa often follows instrumentation of the urinary, respiratory, or gastrointestinal tracts in the hospitalized patient. Mortality still is excessively high. Infections of skin structure, particularly decubitus ulcers in debilitated, bedridden patients, are due to a mixed gram-negative and anaerobic flora; frequently, P. aeruginosa and Enterobacteriaceae resistant to many older agents are the major pathogens. Similarly, osteomyelitis in patients who have undergone previous surgical procedures is caused by various multiply resistant Enterobacteriaceae and P. aeruginosa. In all of these situations, therapy has usually included an aminoglycoside. The availability of drugs such as aztreonam, which has activity directed at aerobic gram-negative bacilli, provides an alternative approach that has proved successful and can be evaluated in more detail in the coming years.

Arthritis, Infectious↗
PubMed1984

Therapeutic activity of ceftazidime and eleven other beta-lactam antibiotics against experimental Haemophilus influenzae, type b meningitis.

Twelve beta-lactams (11 cephalosporins and aztreonam) were compared in an infant rat model of Haemophilus influenzae, type b meningitis. Ceftazidime was the most effective compound tested and showed greater activity than cefuroxime, latamoxef (moxalactam) and cefotaxime--all of which have been used successfully in clinical haemophilus meningitis in children.

Animals↗
PubMed1985

In-vitro antibacterial activity of AMA-1080.

The in-vitro antibacterial activity of AMA-1080 against both Gram-positive and Gram-negative clinical isolates was studied in comparison with that of aztreonam, cefotaxime, ceftazidime and cefoperazone. AMA-1080 showed a potent antibacterial activity against Gram-negative bacteria, particularly, the strains of Enterobacteriaceae. In addition, AMA-1080 inhibited the strains of genus Pseudomonas at the low concentrations. However, AMA-1080 showed less active against Gram-positive bacteria. It was found that AMA-1080 was highly resistant to hydrolysis by both chromosomal and plasmid-mediated beta-lactamases.

Anti-Bacterial Agents↗
PubMed1986

In-vitro antibacterial activity of BO-1165, a new monobactam antibiotic.

BO-1165 has excellent antibacterial activity against Gram-negative bacteria but it is almost inactive against Gram-positive and anaerobic bacteria. BO-1165 was more active than the four reference drugs against Escherichia coli, Salmonella spp., Shigella spp., Klebsiella pneumoniae, Serratia marcescens, indole-positive and indole-negative Proteus. Also, BO-1165 exhibited high antibacterial activity against strains of Pseudomonas aeruginosa (MIC50, 3.12 mg/l) and P. cepacia (MIC50, 1.56 mg/l), but did not against Ps. maltophilia strains. BO-1165 had good stability to plasmid-mediated and chromosome-mediated beta-lactamases. However, the compound was slightly hydrolyzed by the beta-lactamases isolated from Proteus vulgaris, Ps. cepacia, Klebsiella oxytoca and Ps. maltophilia, which were capable of hydrolyzing aztreonam.

Aztreonam↗
PubMed1986

In-vitro evaluation of carumonam (Ro 17-2301).

The in-vitro antibacterial activity of carumonam (Ro 17-2301) was assessed and compared with those of aztreonam and other beta-lactam antibiotics. Carumonam was highly active against the Enterobacteriaceae and Pseudomonas strains resistant to ampicillin (MIC greater than or equal to 256 mg/l) and carbenicillin (MIC greater than or equal to 64 mg/l), respectively. The MICs of carumonam for 90% of the strains ranged between 0.25 mg/l for Klebsiella spp. to 32 mg/l for Pseudomonas spp. The antibacterial activity was minimally altered by changes of medium or inoculum size. Carumonam was resistant to hydrolysis by the plasmid-mediated and chromosomal beta-lactamases tested. Also in the microbiological assay no inactivation was observed. Carumonam was an effective inhibitor of the SHV enzyme and the chromosomal beta-lactamases tested. Against the other plasmid-mediated enzymes carumonam was not an effective inhibitor.

Anti-Bacterial Agents↗
PubMed1990

A comparison of aztreonam/metronidazole and cefotaxime/metronidazole in elective colorectal surgery: antimicrobial prophylaxis must include gram-positive cover.

Aztreonam/metronidazole and cefotaxime/metronidazole were compared in a prospective trial in 154 patients undergoing elective colorectal surgery. Three antibiotic doses were given over 16 hours. A significant excess of wound sepsis in the aztreonam group was seen (23/71 vs 9/70 chi 2 6.60; P less than 0.01). Sepsis was almost invariably due to Gram-positive organisms and, in particular, Staphylococcus aureus.

Aztreonam↗
PubMed1991

In-vitro and in-vivo antimicrobial activities of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain.

The antibacterial activity of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain, was evaluated in vitro and in vivo, with ceftazidime, aztreonam and cefoperazone as the reference antibiotics. CP6162 showed weak or little activity against Gram-positive bacteria, but potent activity against clinical isolates of the Gram-negative species including strains of Pseudomonas aeruginosa, Ps. cepacia, Acinetobacter sp., Xanthomonas maltophilia, Serratia marcescens, Enterobacter cloacae and Citrobacter freundii, which were resistant to the reference antibiotics. The MICs of CP6162 were only slightly affected by the high producers of beta-lactamases except for cephalosporinase-producing C. freundii. It was, however, affected by the presence of ferric ion. CP6162 showed in-vivo activity paralleling the in-vitro activity, and also showed pharmacokinetic parameters similar to those of ceftazidime in mice and rats.

Animals↗
PubMed1993

Reactivity and protective capacity of a polyclonal antiserum derived from mice immunized with antibiotic exposed Escherichia coli.

The murine immune response to Escherichia coli O6:K-alone or pre-exposed to 0.1 x MIC of aztreonam was investigated. Relative to mice immunized with untreated bacteria, mice immunized with antibiotic-treated microorganisms presented a significantly enhanced protection towards a challenge of 100 x LD50 of viable E. coli O6:K-. Previous injection of 0.1 mL of serum drawn from mice immunized with treated and untreated bacteria protected non-immunized mice towards a challenge of 10 x LD50 of viable E. coli O6:K--. Serum from mice immunized with treated bacteria also protected non-immunized mice towards a lethal challenge of E. coli O111. The antiserum contained high titre of IgG antibodies that cross-reacted with lipopolysaccharide isolated from smooth and rough Gram-negative bacteria. Immunoblotting showed additional bands of reactivity to the untreated E. coli O6:K-. Immunization with antibiotic-treated bacteria led to the production of type specific and cross reactive antibodies that protected animals against viable homologous and heterologous lethal challenges.

Animals↗
PubMed1995

In-vitro activities of various antibiotics, alone and in combination with amikacin against Pseudomonas aeruginosa.

The in-vitro activities of various antibiotics, either alone or in combination with amikacin were assessed in clinical isolates of Pseudomonas aeruginosa. Clinically relevant synergic interactions were most frequent with piperacillin (92%), ceftazidime (87%) and aztreonam (84%), and less frequent with imipenem (35%). Ciprofloxacin-amikacin showed only an additive effect.

Amikacin↗
PubMed1996

The effect of aminoglycoside-induced adaptive resistance on the antibacterial activity of other antibiotics against Pseudomonas aeruginosa in vitro.

The effect of gentamicin-induced adaptive resistance on the antibacterial activity of six non-aminoglycoside antibiotics was studied. Adaptive resistance was induced in Pseudomonas aeruginosa in a dynamic in-vitro model of infection. The bactericidal effect of ceftazidime, imipenem, aztreonam, ciprofloxacin, and piperacillin was not altered in the presence of adaptive resistance but the effect of rifampicin was increased.

Anti-Bacterial Agents↗
PubMed1999

In-vitro effects of a combination of antipseudomonal antibiotics against multi-drug resistant Pseudomonas aeruginosa.

We evaluated the in-vitro effects of various combinations of five types of widely used antipseudomonal antibiotics (piperacillin, meropenem, ceftazidime, aztreonam and amikacin) against six Pseudomonas aeruginosa strains that were resistant to each of these antibiotics. Among two-drug combinations, the combinations of two beta-lactam antibiotics inhibited growth of one to three P. aeruginosa strains, while those of one beta-lactam antibiotic and amikacin inhibited growth of two to four strains. Among three-drug combinations, the combinations of three beta-lactam antibiotics inhibited growth of four to five strains, and those of two beta-lactam antibiotics and amikacin inhibited growth of five strains. These results suggest the potential usefulness of a combination of two beta-lactam antibiotics and amikacin or that of three beta-lactam antibiotics in treating multi-drug resistant P. aeruginosa infections.

Amikacin↗
PubMed2006

Treatment of culture-negative skull base osteomyelitis.

OBJECTIVE: To evaluate the efficacy of a therapeutic regimen in the treatment of patients with culture-negative skull base osteomyelitis. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral hospital. PATIENTS: Eight patients with diabetes mellitus presented with otalgia and were found to have positive technetium and gallium scans of the temporal bone. These patients, however, all had negative cultures of their external auditory canals. All patients had been treated with ototopic drops and two patients had undergone a 2-week course of oral quinolones. INTERVENTIONS: All patients were treated with a 6-week course of intravenous ceftazidime or aztreonam for penicillin-allergic patients, oral ciprofloxacin at a higher dose than normal, and topical aminoglycoside steroid drops. MAIN OUTCOME MEASURES: Resolution of the temporal bone gallium scan abnormality, recurrence rate, and time to discharge from the hospital. RESULTS: The patients were discharged from the hospital within 4 days from admission. All patients showed resolution of the temporal bone abnormality on the gallium scan at the 6-week time point. The median follow-up period was 6 months, and none of the patients had a recurrence of the infection. CONCLUSION: The above-described treatment regimen will result in a high cure rate and a short hospitalization period.

Administration, Topical↗
PubMed1994

Murine monoclonal antibody elicited with antibiotic-exposed Escherichia coli exerts protective capacity in experimental bacterial infections.

Escherichia coli pre-exposed to a sub-minimal inhibitory concentration (sub-MIC) of several antibiotics elicits an enhanced humoral response which is protective against challenges with untreated homologous and heterologous bacteria. To characterise the specificity of this response we produced murine monoclonal antibodies (MAbs) to aztreonam-treated E. coli O6:K-. This resulted in the identification of MAb MT 1F, of isotype IgG1, that recognised a 12-kDa protein component of the untreated bacterial cells. After passive transfer, the MAb displayed protective activity in mice infected with lethal doses of live E. coli O6:K- and E. coli O111:B4. In ELISA experiments the MAb cross-reacted with structures located on whole cells of E. coli O6:K-, E. coli O111:B4, E. coli J5 and Salmonella minnesota Re595 and it also exerted a bactericidal activity against live E. coli O6:K-. The modifications induced by antibiotic treatment may unmask bacterial epitopes that may elicit the production of MAbs endowed with protective capacity.

Animals↗
PubMed1997

Characterisation and protective capacity of monoclonal antibodies elicited in mice against protein epitopes of antibiotic-exposed Escherichia coli.

The binding capacity and the protective activity of three monoclonal antibodies (MAbs)-ARM 1-4, ARM 1-7 and ARM 2-2-obtained from spleen cells of mice immunised with Escherichia coli O6:K-pre-treated with sub-MIC of aztreonam were studied. The MAbs belonged to IgG1 isotype and showed different reactivity toward protein epitopes of E. coli in an immunoblotting assay. ARM 1-4 recognised epitopes on molecules of 30 kDa and 40 kDa. ARM 1-7 identified an epitope of a molecule of 41 kDa, and ARM 2-2 recognised epitopes of molecules of 15 kDa and 41 kDa. In ELISA the MAbs cross-reacted with E. coli O7:K-, E. coli O111:B4 and E. coli O128:K- with different binding affinity. Furthermore, the MAbs showed complement-dependent bactericidal activity. The MAbs displayed different protective capacities when given to mice 90 min before lethal challenges with 2 x LD50, 4 x LD50 and 8 x LD50 of E. coli strains. In all but one instance (ARM 1-4 versus E. coli O7:K-) it was not possible to correlate protective capacity with binding affinity of a MAb to a given bacterial cell. Therefore, the epitopes recognised by the MAb may be more closely associated with bacterial virulence than in binding to the bacterial cell.

Animals↗
PubMed2005

Continuous infusion beta-lactams for intensive care unit pulmonary infections.

This study evaluated the pharmacodynamics of continuous infusion beta-lactams against pulmonary isolates of Gram-negative bacteria from patients managed in intensive care units (ICUs) in the USA. Multiple 10,000-patient Monte Carlo simulations were performed by integrating pharmacokinetic data from healthy individuals with 2408 MICs from the 2002 Intensive Care Unit Surveillance System database. These pharmacodynamic simulations suggested that continuous infusion regimens of cefepime, aztreonam, ceftazidime and piperacillin-tazobactam 13.5 g have the greatest likelihood of achieving pharmacodynamic targets against isolates of Enterobacteriaceae in the ICU. Beta-lactams are unlikely to achieve pharmacodynamic targets against Pseudomonas aeruginosa or Acinetobacter baumannii when administered as monotherapy.

Anti-Bacterial Agents↗
PubMed1999

Biochemical and genetic characteristics of TEM-29B, a novel extended spectrum beta-lactamase.

A clinical strain of Escherichia coli (strain Ec 41553) that was resistant to ceftazidime produced a TEM-type beta-lactamase with a pI of 5.4. Clavulanic acid restored the ceftazidime activity, thus suggesting an extended spectrum beta-lactamase (ESBL). The gene encoding ESBL was located in a plasmid of 57 kb. After cloning and sequencing, the ESBL (TEM-29B) showed one amino acid replacement with respect to the TEM-1 sequence, Arg-164 to His. This change increased mainly the rate of hydrolysis of ceftazidime but not of cefotaxime and aztreonam. The relevance of this substitution in the increase of ceftazidime MIC is thus stressed.

Aztreonam↗
PubMed2000

Outbreak of Klebsiella pneumoniae producing transferable AmpC-type beta-lactamase (ACC-1) originating from Hafnia alvei.

Fifty-two strains of Klebsiella pneumoniae producing an AmpC-type plasmid-mediated beta-lactamase were isolated from 13 patients in the same intensive care unit between March 1998 and February 1999. These strains were resistant to ceftazidime, cefotaxime and ceftriaxone, but susceptible to cefoxitin, cefepime and aztreonam. Plasmid content and genomic DNA restriction pattern analysis suggested dissemination of a single clone. Two beta-lactamases were identified, TEM-1 and ACC-1. We used internal bla(ACC-1) primers, to sequence PCR products obtained from two unrelated strains of Hafnia alvei. Our results show that the ACC-1 beta-lactamase was derived from the chromosome-encoded AmpC-type enzyme of H. alvei.

Amino Acid Sequence↗