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PubMed1984

Treatment of serious gram-negative infections with aztreonam.

Aztreonam (SQ 26,776) is the first parenteral monobactam agent to be used in patient trials. The agent has significant activity in vitro against facultative aerobic gram-negative bacteria but not against gram-positive or anaerobic bacteria. Aztreonam was used for a year to treat 106 hospitalized patients with a total of 131 documented gram-negative infections. Important exclusion criteria included granulocytopenia, hyperbilirubinemia, meningitis, patients less than 13 years of age, pregnancy, and history of anaphylaxis to penicillin. In this study of 35 men and 71 women, there were 67 cases of pyelonephritis (25% bacteremic), 19 of pneumonia (16% bacteremic), 10 of skin or soft-tissue infections, 9 cases of osteomyelitis, and 6 cases of postpartum endometritis. During the study period, 159 facultative aerobic gram-negative bacteria were tested for aztreonam susceptibility, and 144 (91%) were found to be susceptible. Eighty percent of infections were cured by both clinical and microbiological criteria and each of the other 26 infections showed clinical improvement. Eradication of the infecting organism was achieved in 89% of infections without adverse reaction or drug toxicity.

Adolescent↗

PubMed1985

Penetration of aztreonam into human cerebrospinal fluid in the presence of meningeal inflammation.

Cerebrospinal fluid of aztreonam were measured in 11 patients with meningeal inflammation. Two to eight hours after a single 2 gm intravenous dose, CSF aztreonam levels ranged from 0.76 to 16.6 mg/l. The mean CSF concentration in four patients with viral meningitis was 1.28 mg/l, which was lower than the mean concentration of 7.2 mg/l in the five with bacterial, cryptococcal or carcinomatous meningitis. Two patients with infected subdural drains were also sampled serially and had CSF levels greater than 1 mg/l between 1 and 8 h post dose. Penetration of aztreonam into the CSF in the presence of meningeal inflammation appears adequate to warrant therapeutic trials in patients infected with susceptible organisms.

Adult↗

PubMed1986

Evaluation of aztreonam, cefoperazone, latamoxef and ceftazidime in the hamster colitis model.

Aztreonam, ceftazidime, cefoperazone and latamoxef (moxalactam) were evaluated in a hamster model for antibiotic-associated colitis. Aztreonam, a novel monocyclic beta-lactam antibiotic specifically directed against aerobic Gram-negative bacteria with limited activity against Gram-positive and anaerobic bacteria did not cause haemorrhagic caecitis and death in hamsters when administered intraperitioneally or orally. Quantitative caecal cultures showed no changes in the anaerobic caecal microflora of hamsters treated intraperitoneally with aztreonam and only a temporary decrease in anaerobic Gram-negative bacilli in hamsters treated orally. Clostridium difficile and its cytotoxin were not present in these animals. Parenteral administration of ceftazidime also did not affect the anaerobic caecal microflora or cause caecitis. However, when given orally, ceftazidime suppressed the anaerobic caecal microflora and a lethal C. difficile-induced caecitis developed. Latamoxef or cefoperazone given parenterally resulted in caecitis and death in five days with marked changes in the anaerobic caecal microflora and C. difficile present in the caecal contents of these animals. The lethal haemorrhagic caecitis observed in this study was indistinguishable from that seen in the clindamycin-induced colitis model in the hamster. The possible correlation of these findings to gastrointestinal disturbances as a complication of antibiotic therapy in humans is discussed.

Administration, Oral↗

PubMed1988

The use of aztreonam in serious gram-negative infections.

Aztreonam, the first available monobactam, was used to treat 38 episodes of serious infection presumed or proven to be due to aerobic Gram-negative bacteria. On 15 occasions it was used empirically in combination with other antibiotics and on 23 occasions as therapy specifically directed against Gram-negative pathogens. Thirty-six Gram-negative infections were documented (including 23 septicaemias) and 35 of them were clinically cured by aztreonam. Likewise 35 of the 36 aerobic Gram-negative pathogens were eradicated. Both of the failures (one clinical and one microbiological were Salmonella infections). No major toxicity was seen but there were five superinfections (four due to Streptococcus faecalis). The results indicate that aztreonam is a useful alternative to the aminoglycosides or the broad-spectrum beta-lactam antibiotics for the treatment of severe Gram-negative infections.

Adolescent↗

PubMed1989

Enhanced in-vitro bactericidal activity of amikacin combined with latamoxef, cefotaxime and aztreonam against multi-resistant Enterobacter cloacae.

The in-vitro interactions of amikacin with latamoxef, cefotaxime and aztreonam were studied for 20 multiresistant strains of Enterobacter cloacae isolated from clinical specimens of nosocomial origin. All the strains were resistant to amikacin, cefotaxime and aztreonam while 14 were resistant and six sensitive to latamoxef. Interactions were studied simultaneously by the killing curve technique after exposure to 16 mg/l of each antibiotic, whenever the MIC was above 16 mg/l and 1/4 the MICs whenever the MIC was less than or equal to 16 mg/l. Enhanced killing was defined as a greater than or equal to 2 log increase in bactericidal effect after three or five and a half or 24 h incubation with both drugs, as compared to the single most effective antibiotic alone. Aztreonam enhanced the rate of killing by amikacin for 13 strains, latamoxef for 12 strains and cefotaxime for 11 strains. For seven strains, all interactions exhibited enhanced killing over time. No antagonism was observed. The interaction results were independent of the MICs as well as of the underlying resistance mechanism to either of the combined antibiotics. The significance of these in-vitro results requires confirmation in vivo.

Amikacin↗

PubMed1989

The influence of cefoperazone, cefotaxime, ceftazidime and aztreonam on phagocytosis by human neutrophils in vitro.

The uptake and intracellular breakdown of Escherichia coli by human neutrophils was studied under the influence of cefoperazone, cefotaxime, ceftazidime and aztreonam. Non-opsonized as well as serum- and IgG-opsonized bacteria were used, and bacteria and neutrophils were exposed both separately before phagocytosis and together during uptake and in the postingestion phase. Preincubation of the neutrophils with the drugs stimulated their subsequent uptake of untreated serum-opsonized and non-opsonized E. coli in an antibiotic-free medium. With serum-opsonized bacteria this stimulating effect was reversed when the drugs were also present during phagocytosis. The uptake of IgG-opsonized bacteria was largely unaffected both after preincubation of the neutrophils and when the antibiotics were present during phagocytosis. With all four drugs, pre-exposure of bacteria before IgG-opsonization gave a much higher uptake than exposure after IgG-opsonization. Contrary to this, preincubation of the bacteria followed by serum-opsonization inhibited (cefotaxime, ceftazidime) or did not influence (cefoperazone, aztreonam) subsequent uptake in the absence of the drugs. The release of bacterial breakdown products from the cells in the postingestion phase was also inhibited by cefotaxime and ceftazidime after serum-opsonization. With non-opsonized and IgG-opsonized bacteria, however, a stimulation of intracellular breakdown was induced by the presence of these drugs during phagocytosis. Aztreonam and cefoperazone did not significantly influence this phase of phagocytosis. These observations suggest that the drugs bind to both neutrophils and bacteria in an individual manner and modify the binding and function of opsonins.

Anti-Bacterial Agents↗

PubMed1989

Intracellular activity of cefamandole and aztreonam against phagocytosed Escherichia coli and Staphylococcus aureus.

The intracellular activity of cefamandole and aztreonam against phagocytosed Escherichia coli and cefamandole against phagocytosed Staphylococcus aureus was studied using a sensitive and standardized method of murine peritoneal macrophages. Cefamandole and aztreonam exerted an intracellular antibacterial activity against E. coli which was greater than their extracellular one. With concentrations of both antibiotics up to 16 x MBC a dose-dependent decrease of the initial number of intracellular E. coli which ranged from 32% to 90% was observed. However, similar antibiotic concentrations above the MBC affected the viability of extracellular E. coli by only 20% to 30%. The intracellular antibacterial activity of both antibiotics against E. coli was further enhanced by immune serum. Cefamandole at 4 x the MBC did not affect the survival of intracellular S. aureus, but killed 41% of extracellular bacteria by 1 h and 99% after 3 h. The intracellular activity of both antibiotics against E. coli was also maintained in NaF-pulsed macrophages which have an impaired oxidative metabolism. The data suggest that both cefamandole and aztreonam possess an intracellular antibacterial activity against E. coli that seems at least in part due to a positive cooperation of antibiotics with the O2-independent microbicidal system of macrophages.

Animals↗

PubMed1991

Characterization of Klebsiella oxytoca septicaemia isolates resistant to aztreonam and cefuroxime.

Eleven clinical isolates of Klebsiella oxytoca from Stockholm hospitals were found to be resistant to aztreonam and cefuroxime, but susceptible to cefotaxime, ceftazidime and imipenem. Resistance could be overcome by combining the beta-lactams with the inhibitor clavulanic acid. Crude beta-lactamase preparations from the isolates inactivated aztreonam and cefuroxime rapidly. By isoelectric focusing, a single common beta-lactamase of pI 5.25 was detected. The K. oxytoca isolates belonged to three subgroups, based on their plasmid profiles and Bg/II restriction endonuclease digestion of plasmid DNA. It was concluded that resistance to aztreonam and cefuroxime in these isolates was conferred by a beta-lactamase distinct from TEM-1, TEM-2 and SHV-1, but possibly derived from TEM-like enzymes.

Aztreonam↗

PubMed1987

Surgically treated gangrenous or perforated appendicitis. A comparison of aztreonam and clindamycin versus gentamicin and clindamycin.

A randomized, double-blinded, controlled clinical study of 84 patients with surgically treated gangrenous or perforated appendicitis was done to compare the efficacy of the combination of aztreonam, the first monobactam antibiotic, with gentamicin when either was combined with clindamycin. Fifty-six patients who were treated with aztreonam and clindamycin (A/C) and 28 patients who were treated with gentamicin and clindamycin (G/C) fulfilled criteria for evaluation. A matched historic control group of 56 G/C patients was also included for comparison. All measures of outcome, including days of fever, hospitalization, antibiotic therapy, and the incidence of antibiotic failures, were similar. It was concluded that aztreonam was as effective as gentamicin in this study and may offer some advantages with regard to toxicity and serum drug level monitoring.

Adult↗

PubMed1989

The role of aztreonam in treatment of complicated urinary tract infections in children.

Urinary tract infections are common among pediatric patients, occurring in approximately 2% of children within the first 5 to 10 years of life. Most urinary tract infections are uncomplicated and respond readily to treatment. However, complications may make treatment difficult and result in serious adverse sequelae. Several characteristics of aztreonam make it an attractive alternative to aminoglycosides and certain other antibiotics for the treatment of complicated urinary tract infections in children. It has been shown, for example, that the drug is highly active against most of the pathogenic organisms responsible for urinary tract infections in the pediatric population, as well as Pseudomonas aeruginosa and many less common, aminoglycoside- and cephalosporin-resistant Gram-negative bacteria. Aztreonam is widely distributed throughout the body and achieves potentially therapeutic concentrations in the kidneys and in urine for up to 24 hours after dosing. The efficacy and safety of this agent compare favorably with standard antibiotic agents. Aztreonam is associated with high rates of microbiologic and clinical cures, and the few side effects reported have been mild and transient.

Aztreonam↗

PubMed1994

Klebsiella oxytoca: resistance to aztreonam by overproduction of the chromosomally encoded beta-lactamase.

Aztreonam-resistant Klebsiella oxytoca strain SL7811 was selected on agar containing 1 microgram of aztreonam per ml from a susceptible strain SL781. The MICs for the resistant mutant towards penicillins, aztreonam and ceftriaxone were much higher, to cefotaxime slightly higher and to ceftazidime unchanged. Synthesis of beta-lactamase was 223-fold greater in the mutant compared with the susceptible strain. SL781 and its resistant mutant SL7811 produced beta-lactamase with the same isoelectric point and substrate profile. The beta-lactamase genes from SL781 and SL7811 were cloned in plasmid pBGS18 giving pBOF-1 and pBOF-4 respectively. The sequences of the two putative promoters indicated two modifications in the resistant plasmid pBOF-4: a transversion (G-->T) in the first base of the -10 consensus sequence and a deletion of one C residue four base pairs upstream of the -10 hexamer.

Amino Acid Sequence↗

PubMed1992

[Aztreonam or gentamicin combined with piperacillin as empiric antibiotic therapy during neutropenia of patients with hematologic diseases].

Fourty-two febrile episodes of 32 patients with hematologic disease during neutropenia were treated with two randomly assigned antibiotic combinations of either piperacillin plus gentamicin or piperacillin plus aztreonam. Eleven of the 22 febrile episodes treated with piperacillin plus gentamicin and 12 of the 20 febrile episodes treated with piperacillin plus aztreonam responded. Addition of cefamandole to non-responders improved the outcome in 2 of the 16 febrile episodes. Mean nadir leucocyte count, age, sex, and underlying disease were not significantly different in both groups. Side effects were tolerable in both groups, although 1 patient treated with piperacillin plus gentamicin showed severe renal impairment. Piperacillin plus aztreonam is as effective as piperacillin plus gentamicin as an empiric antibiotic combination in the treatment of febrile episodes with hematologic disease during neutropenia.

Adolescent↗

PubMed1983

Pharmacokinetics of aztreonam in rabbit eyes.

Subconjunctival injection of 100 mg of aztreonam in rabbits with Pseudomonas aeruginosa endophthalmitis produced transiently high antibiotic concentrations in most intraocular sites. Concentrations of approximately 2.5 micrograms/ml were achieved in the vitreous humor 15 min after injection and persisted for 6 h. Repeated intramuscular injections in dosages of 25 mg/kg every 4 h resulted in drug concentrations in the vitreous humor of 2.4 micrograms/ml in infected eyes. These levels might be adequate for the treatment of intraocular infections caused by highly susceptible organisms. Direct intravitreal injection of 100 micrograms of aztreonam in normal rabbit eyes produced an estimated peak concentration in the vitreous humor of 62 micrograms/ml, with a half-life of 7.5 h, which declined to 6 micrograms/ml by 48 h. The pharmacokinetic indices suggest that, like other beta-lactam antibiotics, aztreonam is eliminated from the vitreous humor by the retinal route. This novel antibiotic warrants further study of its efficacy and toxicity to determine whether it may be a useful alternative to the aminoglycosides for selected cases of ocular infection.

Animals↗

PubMed1984

In vitro activity of aztreonam in combination with newer beta-lactams and amikacin against multiply resistant gram-negative bacilli.

The in vitro synergistic activity of aztreonam in combination with piperacillin, moxalactam, cefotaxime, cefoperazone, and amikacin was examined against multiply resistant isolates of the family Enterobacteriaceae and Pseudomonas aeruginosa. Aztreonam in combination with amikacin demonstrated synergy against 71% of the isolates, whereas combinations of aztreonam plus a second beta-lactam demonstrated synergy against 42% of the isolates.

Amikacin↗

PubMed1984

Aztreonam concentrations in human prostatic tissue.

The concentrations of aztreonam in human prostatic tissue specimens obtained by transurethral resection were measured in nine patients after the intramuscular administration of a single 1-g dose. The average concentration of aztreonam was 7.8 microgram/g of prostate between 50 and 180 min after dosage. The average ratio of the drug concentration in prostate to that in serum was 0.25. The concentrations of aztreonam achieved were significantly higher than the MICs for most members of the family Enterobacteriaceae implicated in chronic prostatitis.

Adult↗

PubMed1984

Comparative activities of aztreonam and cefotaxime against Escherichia coli and Bacteroides spp. in pure and mixed cultures.

The activities of aztreonam and cefotaxime against one Escherichia coli strain and three Bacteroides strains have been studied by using pure and mixed cultures of aerobic and anaerobic bacteria. A fixed concentration (8 micrograms/ml) of cefotaxime or aztreonam killed E. coli that was exposed in pure culture, but the pressure of Bacteroides spp. in the same system deteriorated cefotaxime, allowing the full growth of E. coli after 24 h. On the other hand, the presence of Bacteroides spp. produced less deterioration of aztreonam, which reduced the initial E. coli inoculum. This observation could be useful in clinical practice when treating mixed aerobic and anaerobic infections.

Anti-Bacterial Agents↗

PubMed1985

Effectiveness of aztreonam for the treatment of gonorrhea.

Aztreonam, 1 g intramuscularly, was compared with spectinomycin, 2 g intramuscularly, for uncomplicated gonorrhea. There were no failures with either drug. For aztreonam, there were 26 urethral, 3 rectal, and 3 endocervical sites that were infected. Aztreonam in a single dose of 1 g intramuscularly is satisfactory therapy for uncomplicated urethral gonorrhea in men and may be effective for rectal and endocervical infection as well.

Adolescent↗

PubMed1985

Evaluation of aztreonam in the treatment of severe bacterial infections.

We investigated the clinical efficacy and safety of aztreonam in the treatment of 50 episodes of infection in 46 adult patients. The clinical condition of patients at the beginning of treatment was critical or poor in 28 of the episodes of infection. Episodes treated were 39 urinary tract infections (12 of them with concomitant bacteremia), 2 soft tissue infections, 8 patients with osteomyelitis (1 with concomitant bacteremia), and one episode of pneumonia. Significant isolated microorganisms were aerobic or facultative gram-negative rods and were responsible for the following episodes of infection (number of episodes): members of the family Enterobacteriaceae (49), Pseudomonas aeruginosa (5), and Haemophilus influenzae (1). The overall rate of clinical response to aztreonam was 94% of the treated episodes. Colonization or superinfection or both occurred in 29 episodes, but only 8 episodes required antimicrobial therapy. Aztreonam seems to be an effective single agent therapy for many bacterial infections. Colonization and superinfection by Candida sp., Streptococcus faecalis or Staphylococcus aureus must be monitored.

Adolescent↗