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Of 108 consecutive patients with urogenital gonorrhoea treated with a single 1 g intramuscular dose of aztreonam, 102 were suitable for evaluation. There was 100% cure at urogenital sites but treatment failed at three of 14 (21%) rectal or pharyngeal sites. In vitro resistance to aztreonam was not noted.
Regression lines and error rate-bounded analyses were performed for correlating inhibitory zone diameters with the 30-micrograms aztreonam disk and aztreonam minimal inhibitory concentration for gram-negative aerobic clinical isolates. A correlation coefficient of -0.81 was found for the regression line. Preliminary proposed criteria to distinguish susceptible isolates from resistant ones are: susceptible greater than or equal to 22 mm (MIC less than or equal to 8 micrograms/ml), intermediate 16-21 mm (MIC = 16 micrograms/ml) and resistant less than or equal to 15 mm (MIC greater than or equal to 32 micrograms/ml). Using these criteria, the rates for false-susceptible and false-resistant isolates were zero.
The susceptibility of 310 mainly clinically isolated Gram-negative nonfermenters to aztreonam, carumonam, ciprofloxacin, ofloxacin and fleroxacin was determined by agar dilution. All 3 quinolones were very active, with MIC90 ranges (micrograms/ml) against all organisms ranging between 0.25 and 8 for ciprofloxacin, and 0.25 and 16.0 for ofloxacin and fleroxacin, respectively. Aztreonam and carumonam showed less activity than the quinolones on a weight-for-weight basis, with MIC90 values ranging from 4 to 32 for both drugs; only Pseudomonas aeruginosa and Acinetobacter calcoaceticus biotypes haemolyticus and alcaligenes were uniformly susceptible to both monobactams. The broad-spectrum activity of the 3 quinolones suggests potential use in therapy of infections caused by nonfermenters; monobactams should be reserved for infections caused by P. aeruginosa and possibly Acinetobacter spp.
The combination aztreonam + cefotaxime (AZ + CE) was compared to amikacin + cefotaxime (AM + CE) in the treatment of nosocomial pneumonia acquired at the intensive-care unit. This study included a total of 33 patients fulfilling criteria for nosocomial pneumonia. 16 of them were randomly allocated to the AZ + CE group and 17 to the AM + CE group. The empirical treatment was effective for 78% of AZ + CE cases and 92% of AM + CE cases (p = NS). Clinical care was observed in 77% of cases (10 out of 13 evaluable) in the AZ group and in 75% of the group treated with AM (12 cases out of 16 evaluable; p = NS). In the evaluable cases, treatment failure was associated with injections due to the following organisms: Acinetobacter calcoaceticus (1) and Pseudomonas aeruginosa (1) in the AZ group and A. calcoaceticus (1) in the AM group. Superinfections were observed only in the AM group P. aeruginosa. A. calcoaceticus, Streptococcus viridans, Candida albicans, Aspergillus fumigatus and Serratia marcescens. Both the peak and through serum concentrations of AZ and AM were maintained within normal ranges. Finally, an impairment of renal tubular function was observed in the group of patients treated with AM, as measured by urinary levels of N-acetyl-beta-D-glucosaminidase and leucine aminopeptidase sequentially during the treatment. These changes in renal functions alterations mentioned were not observed in the AZ group. It is concluded that the AZ + CE combination is an effective empirical and active antibiotic treatment against severe nosocomial pneumonia. Aztreonam has no renal toxicity, which is an advantage to take into account in patients with altered renal function.
Aztreonam was administered to 20 children diagnosed as having any of the following infections: urinary tract infection, pneumonia, meningitis, and abscess of the appendix. Haemophilus influenzae, Escherichia coli, and Klebsiella pneumoniae were isolated. The minimum inhibitory concentrations of aztreonam for these bacteria ranged from 0.03 to 0.5 micrograms/ml. All patients were clinically and bacteriologically cured within 5-16 days of treatment. Six months after completion of therapy, patients who had had meningitis appeared to be free of any neurologic sequelae. The antibiotic was well tolerated by all patients.
The monobactam aztreonam was used to treat 22 young patients with meningitis caused by gram-negative bacilli. Haemophilus influenzae was isolated from the CSF of 21 patients and Salmonella heidelberg from the CSF of 1. Dosages ranged from 100 to 200 mg/kg/day in 4 doses at 6-hour intervals. Minimal inhibitory concentrations were determined by the broth dilution method for all isolated strains, and values ranged from 0.05 to 2.0 micrograms/ml. Blood and CSF drug levels were determined by a microbiologic plate diffusion method, and mean values for CSF and blood were 1.4 and 14.9 micrograms/ml, respectively. The outcome was good in 21 patients; 1 patient died. Complications were mild; subdural effusion occurred in 6 cases and was managed clinically; asymptomatic hydrocephalus was seen in 4; seizure during the acute phase occurred in 6 cases; hypoacusis was noted in 2, and motor impairment was detected at the follow-up in 1 case. Aztreonam achieved good blood and CSF penetration and performed well in the treatment of 20 cases of H. influenzae meningitis and in the one case of S. heidelberg meningitis.
One hundred ten patients were randomized to receive one of the following antibiotic combinations: aztreonam + clindamycin, tobramycin + clindamycin, or amikacin + mezlocillin for the treatment of lower respiratory tract infections (LRTI) caused by gram-negative bacilli. Of the 68 patients who received aztreonam + clindamycin, 60 were clinically evaluable and 50 were bacteriologically evaluable. Of the 60 clinically evaluable patients, 54 were cured and 5 were treatment failures or died during the study period. Of the 50 bacteriologically evaluable patients, 46 were cured and 3 failed to respond to therapy. Of the 26 clinically evaluable patients in the tobramycin + clindamycin group, 22 were cured and 4 either failed to respond or died during the study period. Of 18 bacteriologically evaluable patients in this group, 16 were cured and 2 failed to respond. In the amikacin + mezlocillin group, 14 of the 15 clinically and bacteriologically evaluable patients were cured, and 1 failed to respond. The most commonly isolated pathogens were Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. The very few adverse drug reactions that were seen were transient and comparable in all three groups except for renal function parameters, which deteriorated in 6-8% of patients receiving the aminoglycoside combination. All three antibiotic combinations were similar in effectiveness and safety.
Bacteriophage AP-151, isolated from a multidrug resistant Pseudomonas aeruginosa strain, was found to transduce antibiotic resistance determinants to recipient strains of P. aeruginosa. Resistance to cefotaxime, ceftazidime, aztreonam, imipenem and meropenem was transduced as a block, at different frequencies, to two P. aeruginosa strains. Resistance was two logarithms higher (in the range 10(-5)) for cefotaxime, ceftazidime or aztreonam than for imipenem in recipient strain PAO-1670. The frequency of transduced imipenem resistance was also lower in recipient strain ML-1008. This phenomenon reflects the difference in the lytic activity of AP-151 in both strains, as the titer of the AP-151 phage in the PAO strain was found to be restricted to 10(-4)-10(-5) in contrast to the titer of the same phage in the ML strain which was 10(-10). The limited lytic activity in the PAO recipient strain was correlated with higher transducing activity. It can be concluded that some wild-type bacteriophages of P. aeruginosa might have highly individual relations between lytic and transducing activity in various potential recipient nosocomial strains of P. aeruginosa. The nature of resistance to ceftazidime and imipenem was studied using clavulanate and EDTA as inhibitors of individual class of beta-lactamases, indicating the presence of extended-spectrum beta-lactamase and a metallo-beta-lactamase in this isolate.
We evaluate the antimicrobial interactions between aztreonam and selected beta-lactams when tested against metallo-beta-lactamase (MbetaL)-producing clinical strains. Ten Pseudomonsa aeruginosa strains, including nine MbetaL-producers (IMP-1, -2, -13, -16, VIM-1, -2, -7, SPM-1 and GIM-1) and five Acinetobacter baumannii strains, including three MbetaL-producers (IMP-1 and -2) were tested using time kill/bactericidal activity methods. Aztreonam at 4, 8 and 16 mg/L was combined with four other beta-lactam antimicrobials (cefepime, ceftazidime, meropenem and piperacillin/tazobactam or ampicillin/sulbactam), each tested at the recognized susceptible breakpoint concentration. Enhanced activity (synergism or additive effect) was observed with four P. aeruginosa strains (IMP-16, VIM-2, SPM-1 and GIM-1 containing strains) and four A. baumannii strains, while antagonism was observed with two P. aeruginosa (IMP-16 and SPM-1-producing strains) and one A. baumannii (non-MbetaL) strain. All other strains showed indifferent interaction (variation of +/- 1 log10 CFU/ml) with any combination evaluated.
33 patients undergoing colorectal surgery were treated prophylactically with aztreonam (19 patients), moxalactam (10 patients) and ampicillin plus sulbactam (4 patients). The effect on the normal oropharyngeal microflora and new colonization of oropharynx were studied during and after the treatment. Aztreonam had minor effect on the normal flora but induced colonization with staphylococci. Moxalactam suppressed gram-negative aerobic and anaerobic bacteria and promoted colonization with Candida albicans. Ampicillin plus sulbactam had marked effect on the normal flora and suppressed aerobic as well as anaerobic bacteria. New colonization with enteric gram-negative rods or fungi was observed in all patients.
13 children, 8 girls and 5 boys, aged 2-15 months (mean 8.5 months), with Haemophilus influenzae meningitis were treated with aztreonam. Aztreonam was administered intramuscularly in a dose of 50 mg/kg every 8 h. 10 of the infants were in coma and 3 were drowsy when first examined in hospital. All except 2 infants, who were in coma and who died within 24 h of starting therapy, recovered quickly. All patients became fully alert within 4-5 days and afebrile within 5 to 6 days.
Aztreonam treatment was successful in 4 cases of typhoid fever. The patients were seriously ill with growth of Salmonella typhi in blood cultures despite treatment with chloramphenicol. Aztreonam appears to be a useful alternative to standard therapy of typhoid fever.
143 aplastic episodes with fever in 91 haematological patients with granulocytopenia were treated empirically in a randomized prospective study using either imipenem (Imi) or a combination of tobramycin and cefuroxime (T/C). Response after 72 h was significantly better in patients receiving Imi (44/75 vs 27/68, p < 0.05). This was seen especially in patients with bacteriologically proven infections where the isolated staphylococci and streptococci were more susceptible to Imi. In both groups, patients who failed to respond to the initial antibiotic therapy were given vancomycin and aztreonam (V/A). The response rate after another 72 h, measured using the same criteria as after the first 72 h, did not differ statistically between the groups. One patient in each study group died from the bacterial infection, both from Gram-positive bacteraemia. Duration of fever was significantly shorter in the Imi group (4 days vs 7 days, p < 0.04). Serum peak and trough concentrations of the antibiotics were comparable. Both regimens were well tolerated. Our results show that monotherapy with imipenem is superior to the combination of tobramycin and cefuroxime during the first 72 h of therapy and can be safely administered to neutropenic patients with predominantly Gram-positive infections. A combination of vancomycin and aztreonam, given when initial imipenem treatment has failed, was effective in only a few patients. Adjuvant glycopeptide therapy from the outset in the treatment of febrile granulocytopenic patients did not seem worthwhile.
A 24 year old Saudi housewife was admitted thrice with life threatening community acquired pneumonia. Even though she responded to an initial cocktail of cefriaxone, erythromcin, rifampicin and flucloxacillin during the second admission, she relapsed within four days of discharge when she was on erythromycin only. During the third admission she was put on ceftriaxone and aztreonam and recovered fully without any relapse. Serology results received later showed Legionella IgM titres of more than 1:256 for Legionella micdadei and Legionella bozemanii, and IgG titres of Legionella hackeliae. This case demonstrates relapsing pneumonia due to Legionella micdadei and bozemanii infection, and previous exposure to Legionella hackeliae. Both species, that is, Legionella micdadei and bozemanii, are resistant to erythromycin, but responded very well to a combination of ceftriaxone and aztreonam have not been used previously for the treatment of Legionnaires diseases.
Aztreonam belongs to the monobactam group of naturally occurring antibiotic compounds characterized by a monocycling ring structure. Aztreonam is the first monobactam that has been approved for use in pediatric medicine by US FDA in the year 1998.
Personal experience in peroperative antibiotic prophylaxis with aztreonam (Azactam) in 81 patients undergoing abdominal surgery of choice is reported. The usefulness, handiness and lack of side-effects of this parenteral drug are reiterated. The incidence of surgical wound infections was 2.5%, while that of associated infections was 6.1%. Considering these results, the use of aztreonam (Azctam) is recommended in peroperative prophylaxis as a drug of choice.
P. aeruginosa is highly resistant to a wide range of antimicrobial agents. This intrinsic resistance mainly depends on the rate of permeation across the outer membrane (o.m.). In order to promote antibiotic uptake across the hydrophilic channel of the o.m. porins, a permeator can be used with a hydrophilic antibiotic. In the present study we assess the o.m. electrophoretic profile of three P. aeruginosa strains cultured with and without antibiotic Aztreonam and Netilmicin (A:N) using the MIC concentration in the association (3:1). The observed increase in the band can be referred to the F porin when the strains are treated with Aztreonam.
Aztreonam is the first monobactam available for use in this country. A parenteral antibiotic, its antibacterial spectrum is limited to gram-negative aerobic pathogens. The drug's pharmacologic, pharmacokinetic, and toxicologic properties are reviewed. Based on early experience in pediatric patients, certain recommendations can be made for the use of aztreonam.