Combination Of Aztreonam Research Articles

Efficacy evaluation of aztreonam in combination with cefepime for the treatment of urinary tract infectious

Objective To explore the clinical efficacy of aztreonam in combination with cefepime for the treatment of urinary tract infections.Methods A randomized block grouping,123 cases of urinary tract infections were divided into observation group,aztreonam group and cefepime group,41 cases in each group.The observation group was treated with aztreonam (2.0g) and cefepime (2.0g),control group were given aztreonam and cefepime,respectively.The treatment time lasted 7 days.Results The total effective rate of observation group was 95.1％,compared with cefepime(85.4％)or aztreonam(82.9％) group,the difference was statistically significant(x2 =12.89、13.56,all P ＜ 0.05).After the end of treatment,the observation group bacterial clearance rate (94.3％) was slightly higher than that of cefepime group or aztreonam group.Each group had only minor adverse reaction,which did't affect the continued medication.And the difference in the incidence was not statistically significant(P ＞0.05).Conclusion Cefepime joint aztreonam in the treatment of urinary tract infection can improve the therapeutic efficacy,and adverse events doesn't increase. Key words: Urinary tract infections ; Aztreonam; Cefepime

Human Simulated Studies of Aztreonam and Aztreonam-Avibactam To Evaluate Activity against Challenging Gram-Negative Organisms, Including Metallo-β-Lactamase Producers

Secondary to the stability of aztreonam against metallo-β-lactamases, coupled with avibatam's neutralizing activity against often coproduced extended-spectrum β-lactamases (ESBLs) or AmpC enzymes, the combination of aztreonam and avibactam has been proposed as a principal candidate for the treatment of infections with metallo-β-lactamase-producing Gram-negative organisms. Using the neutropenic-mouse thigh infection model, we evaluated the efficacy of human simulated doses of aztreonam-avibactam and aztreonam against 14 Enterobacteriaceae and 13 Pseudomonas aeruginosa isolates, of which 25 produced metallo-β-lactamases. Additionally, six P. aeruginosa isolates were also evaluated in immunocompetent animals. A humanized aztreonam dose of 2 g every 6 h (1-h infusion) was evaluated alone and in combination with avibactam at 375 or 600 mg every 6 h (1-h infusion), targeting the percentage of the dosing interval in which free-drug concentrations remained above the MIC (fT>MIC). Efficacy was evaluated as the change in bacterial density after 24 h compared with the bacterial density at the initiation of dosing. Aztreonam monotherapy resulted in reductions of two of the Enterobacteriaceae bacterial isolates (aztreonam MIC, ≤ 32 μg/ml; fT>MIC, ≥ 38%) and minimal activity against the remaining isolates (aztreonam MIC, ≥ 128 μg/ml; fT>MIC, 0%). Alternatively, aztreonam-avibactam therapy resulted in the reduction of all 14 Enterobacteriaceae isolates (aztreonam-avibactam MICs, ≤16 μg/ml; fT>MIC, ≥ 65%) and no difference between the 375- and 600-mg doses of avibactam was noted. Similar pharmacodynamically predictable activity against P. aeruginosa was noted in studies with neutropenic and immunocompetent mice, with activity occurring when the MICs were ≤ 16 μg/ml and variable efficacy noted when the MICs were ≥ 32 μg/ml. Again, no difference in efficacy between the 375- and 600-mg doses of avibactam was observed. Aztreonam-avibactam represents an attractive treatment option for infections with metallo-β-lactamase-producing Gram-negative pathogens that coproduce ESBLs or AmpC.

Carbapenem-associated multidrug-resistant Acinetobacter baumannii are sensitised by aztreonam in combination with polyamines

Carbapenem-associated multidrug-resistant Acinetobacter baumannii (MDR-Ab) are common among clinical isolates worldwide and are a major therapeutic challenge. Previously it was shown that exogenous polyamines (spermine and spermidine) enhanced susceptibility to β-lactams but induced resistance to polymyxins in Pseudomonas aeruginosa. This study aimed to explore the possible availability of exogenous polyamines in treating carbapenem-associated MDR-Ab. The effects of polyamines on the growth rate of A. baumannii, minimum inhibitory concentrations (MICs) of antibiotics, and time–kill and chequerboard assays were determined. Roles of lipopolysaccharide (LPS) and β-lactamase activity of A. baumannii were also assessed for the polyamine effects. Growth of A. baumannii was unaffected at 4mM spermine and 16mM spermidine alone, but was significantly inhibited by a subinhibitory concentration of aztreonam (AZT) (8μg/mL) and those concentrations of the polyamines. MICs to AZT alone (≥128μg/mL) were reduced to the range 0.25–8μg/mL in combination with polyamines in all carbapenem-associated MDR-Ab. MICs to penicillins, but not to ceftazidime and meropenem, were also significantly reduced, whilst MICs to other antibiotics, including polymyxin B, were unaffected in combination with polyamines for all tested A. baumannii. Polyamine effects on AZT were strongly synergistic with bactericidal activity and were retained at concentrations of 5mM MgCl2 (or CaCl2) or 200mM NaCl. Roles of LPS and β-lactamase in the polyamine effects were excluded. Overall results suggest that AZT in combination with polyamines may be useful for the treatment of carbapenem-associated MDR-Ab.

In vitro evaluation of tobramycin and aztreonam versus Pseudomonas aeruginosa biofilms on cystic fibrosis-derived human airway epithelial cells

Aztreonam for inhalation solution (AZLI) was recently approved by the FDA for treating cystic fibrosis (CF) patients infected with Pseudomonas aeruginosa. Here we investigated the effect of aztreonam alone or in combination with tobramycin on P. aeruginosa biofilms grown on CF airway epithelial cells. P. aeruginosa biofilms, produced by laboratory strains or clinical isolates, were formed on confluent CF airway cells before treatment overnight with aztreonam or tobramycin alone or in combination. Alternatively, antibiotics were added 1 h after bacterial inoculation to assess their ability to impair biofilm formation at 5 h. Bacterial cfu remaining after treatment were then determined by plate counting. In the absence of antibiotics, all strains developed biofilms that disrupted CF airway epithelial monolayers overnight. Tobramycin reduced the cfu of all strains grown as biofilms. Aztreonam reduced the cfu of some strains by ∼1 log unit without preserving the integrity of cystic fibrosis airway cell monolayers, while decreasing the biofilms of other clinical isolates by ∼4 log units and protecting the monolayers from being compromised. The combination of aztreonam and tobramycin reduced the cfu of two strains by an additional 0.5 and 2 log units, respectively. Of all the mechanisms explored, Psl exopolysaccharide production might explain the variations in biofilm tolerance to aztreonam in some of the strains. Effects of aztreonam on P. aeruginosa biofilms in the in vitro co-culture model are strain-dependent. The simultaneous application of aztreonam and tobramycin may be beneficial for a subset of CF patients by eliminating susceptible P. aeruginosa strains.

CANVAS 2: the second Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections

New therapies for complicated skin and skin structure infections (cSSSIs) are needed because of significant morbidity and increasing antimicrobial resistance. Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of cSSSIs. Ceftaroline fosamil, a novel parenteral cephalosporin with excellent in vitro activity against Gram-positive pathogens, including MRSA, and many Gram-negative pathogens, was evaluated as therapy for cSSSIs in a multinational Phase III study. The primary study objective was to determine non-inferiority [lower limit of 95% confidence interval (CI), -10%] in the clinical cure rate of ceftaroline fosamil monotherapy to that achieved with vancomycin plus aztreonam combination therapy in the clinically evaluable (CE) and modified intent-to-treat (MITT) analysis populations. Adult patients with cSSSIs requiring intravenous therapy received 600 mg of ceftaroline fosamil every 12 h or 1 g of vancomycin plus 1 g of aztreonam every 12 h for 5-14 days (randomized 1 : 1). Clinical and microbiological response, adverse events (AEs) and laboratory tests were assessed. Registration number NCT00423657 (http://clinicaltrials.gov/ct2/show/NCT00423657). The study enrolled 694 patients, 348 of whom received ceftaroline fosamil and 346 of whom received vancomycin plus aztreonam. The treatment groups had comparable baseline characteristics. Clinical cure rates for the ceftaroline fosamil and vancomycin plus aztreonam groups were similar in the CE (92.2%, 271/294 versus 92.1%, 269/292; 95% CI, -4.4, 4.5) and MITT (85.1%, 291/342 versus 85.5%, 289/338; 95% CI, -5.8, 5.0) populations, respectively. MRSA cSSSIs were cured in 91.4% (64/70) of patients in the ceftaroline fosamil group and 93.3% (56/60) of patients in the vancomycin plus aztreonam group. The microbiological success rate in the microbiologically evaluable population was 92.9% and 95.0% for ceftaroline fosamil and vancomycin plus aztreonam, respectively. Ceftaroline fosamil and vancomycin plus aztreonam had similar rates of AEs, serious AEs and discontinuations because of an AE. The most common AEs for ceftaroline fosamil and vancomycin plus aztreonam included diarrhoea (6.5% versus 4.4%), nausea (6.2% versus 5.6%), headache (5.3% versus 5.3%) and pruritus (3.8% versus 8.3%), respectively. Ceftaroline fosamil demonstrated high clinical cure and microbiological success rates, was efficacious against cSSSIs caused by MRSA and other common cSSSI pathogens and was generally well tolerated. Monotherapy with ceftaroline fosamil has the potential to provide an alternative treatment for cSSSIs.

Integrated Analysis of CANVAS 1 and 2: Phase 3, Multicenter, Randomized, Double‐Blind Studies to Evaluate the Safety and Efficacy of Ceftaroline versus Vancomycin plus Aztreonam in Complicated Skin and Skin‐Structure Infection

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of complicated skin and skin-structure infection (cSSSI). Increasing antimicrobial resistance in cSSSI has led to a need for new safe and effective therapies. Ceftaroline was evaluated as treatment for cSSSI in 2 identical phase 3 clinical trials, the pooled analysis of which is presented here. The primary objective of each trial was to determine the noninferiority of the clinical cure rate achieved with ceftaroline monotherapy, compared with that achieved with vancomycin plus aztreonam combination therapy, in the clinically evaluable (CE) and modified intent-to-treat (MITT) patient populations. Adult patients with cSSSI requiring intravenous therapy received ceftaroline (600 mg every 12 h) or vancomycin plus aztreonam (1 g each every 12 h) for 5-14 days. Of 1378 patients enrolled in both trials, 693 received ceftaroline and 685 received vancomycin plus aztreonam. Baseline characteristics of the treatment groups were comparable. Clinical cure rates were similar for ceftaroline and vancomycin plus aztreonam in the CE (91.6% vs 92.7%) and MITT (85.9% vs 85.5%) populations, respectively, as well as in patients infected with MRSA (93.4% vs 94.3%). The rates of adverse events, discontinuations because of an adverse event, serious adverse events, and death also were similar between treatment groups. Ceftaroline achieved high clinical cure rates, was efficacious against cSSSI caused by MRSA and other common cSSSI pathogens, and was well tolerated, with a safety profile consistent with the cephalosporin class. Ceftaroline has the potential to provide a monotherapy alternative for the treatment of cSSSI. ClinicalTrials.gov identifiers: NCT00424190 for CANVAS 1 and NCT00423657 for CANVAS 2.

Intérêt de l’association ceftazidime et aztréonam dans les exacerbations de mucoviscidose àPseudomonas aeruginosa multirésistant

Antibiotic therapy for acute pulmonary exacerbations in patients with cystic fibrosis is usually chosen based on the results of antimicrobial susceptibility. This can be difficult when bacteria are multiresistant. The objective of this retrospective study was to evaluate the tolerance and efficiency of ceftazidime and aztreonam combination (+/-tobramycin, +/-ciprofloxacin) in the treatment of acute exacerbations in cystic fibrosis patients who were chronically colonized with multiresistant P. aeruginosa.Seventeen severe patients, with FEV(1)=1070+/-66 mL and BMI=18+/-0.6 kg/m(2), who had chronic colonisation with P. aeruginosa with intermediate sensitivity or resistance to ceftazidime and aztreonam, were studied between June 2003 and March 2007. Oxygen saturation, dyspnoea, weight, FEV(1), FVC, and tolerance were evaluated before and after antibiotic courses.Forty-two courses of treatment, administered between June 2003 and March 2007 were studied: Patients increased their FEV(1) and FVC (p=0.01). One antibiotic course was stopped after four days because of cutaneous side effects. The median delay until the next exacerbation was 101+/-10 days. These courses were compared with other combinations of antibiotics that the patients had received before. The combination of ceftazidime and aztreonam was more effective in patients receiving less than four courses per year for acute pulmonary exacerbation.In chronically P. aeruginosa colonised cystic fibrosis patients, ceftazidime and aztreonam combination (+/-tobramycin, +/-ciprofloxacin) is well tolerated and efficient. This treatment suggests a clinical and functional benefit is possible, even in patients with severe disease.

In vitro antimicrobial effects of aztreonam, colistin, and the 3-drug combination of aztreonam, ceftazidime and amikacin on metallo-β-lactamase-producing Pseudomonas aeruginosa

BackgroundThere are limited choice of antimicrobial agents to treat infection with metallo-β-lactamase-producing Pseudomonas aeruginosa. We evaluate the antimicrobial effects of aztreonam alone, colistin alone and the 3-drug combination of aztreonam, ceftazidime and amikacin on 23 strains of metallo-β-lactamase-producing P. aeruginosa by time-killing tests.MethodsStrains used were from different hospitals in Japan and had different pulse-field gel electrophoresis patterns by restriction with SpeI. The minimum inhibitory concentrations of 11 antimicrobial agents (piperacillin, piperacillin/tazobactam, imipenem, meropenem, aztreonam, ceftazidime, amikacin, tobramycin, arbekacin, ciprofloxacin and colistin) were determined using the agar dilution test. The effects of aztreonam, colistin and the combination of aztreonam, ceftazidime and amikacin were determined by time-killing studies.ResultsBacteriostatic effects after 6 hours of drug exposure were observed in 12 strains (52.2%) of 23 strains of metallo-β-lactamase-producing P. aeruginosa with 48 mg/l aztreonam, in 19 strains (82.6%) with the 3-drug combination of 16 mg/l aztreonam, 16 mg/l ceftazidime, and 4 mg/l amikacin, and in 23 strains (100%) with 2 mg/l colistin. Bactericidal effects after 6 h drug exposure were observed in 1 strain (4.3%) with 48 mg/l aztreonam, in 8 strains (30.4%) with the 3-drug combination and in all 23 strains (100%) with 2 mg/l colistin.ConclusionEvaluation of in vitro antimicrobial effects on metallo-β-lactamase-producing P. aeruginosa revealed relatively good effects of the 3-drug combination of aztreonam, ceftazidime and amikacin and marked effects of colistin.

Antimicrobial Effects of Drugs against Multidrug-Resistant Pseudomonas aeruginosa

We evaluated the effects of antimicrobial drugs on four strains of Pseudomonas aeruginosa that are resistant to eight widely used antipseudomonal drugs (piperacillin, piperacillin-tazobactam, imipenem, meropenem, ceftazidime, aztreonam, amikacin, ciprofloxacin) and colistin. In the killing test, colistin (2 microg/ml) was the most effective, followed by aztreonam (48 microg/ml), piperacillin-tazobactam (192-4 microg/ml), piperacillin (192 microg/ml), and a three drug combination of azetreonam (16 microg/ml), ceftazidime (16 microg/ml), and amikacin (4 microg/ml). Six hours after drug addition, colistin (2 microg/ml), aztreonam (48 microg/ml), piperacillin-tazobactam (192-4 microg/ml), piperacillin (192 microg/ml), and the above three drug combination had bacteriostatic effects on all four strains. Colistin, three time breakpoint of aztreonam, piperacillin, or piperacillin-tazobactam, and the three drug combination of aztreonam, ceftazidime, and amikacin were effective in vitro.

Antibiotic synergy against biofilm-forming Pseudomonas aeruginosa

Eight antibiotics (aztreonam, ceftazidim, cefoperazon, cefepim, netilmicin, amikacin, ofloxacin and ciprofloxacin) exhibited antimicrobial activity individually and/or in combinations against 20 wild-type biofilm-forming strains of Pseudomonas aeruginosa. The strains were less susceptible in biofilm; in 10 strains antibiotic synergy was observed for the combination of aztreonam and ciprofloxacin. Synergy was also demonstrated in the case of beta-lactams and aminoglycosides, beta-lactams and fluoroquinolones, aminoglycosides and fluoroquinolones, and for monobactams and beta-lactams although the strains were resistant to the individual antibiotics. Synergism or partial synergism was found with one or more antibiotic combinations against 32.4% of isolates.

Successful treatment of Acinetobacter meningitis with meropenem and rifampicin

in a rat model of pneumonia. This supports these results and suggests that the combination of aztreonam and fosfomycin is a potential combination regimen effective against MBL-producing Gram-negative bacteria. However, this report also strengthens the fact that detection of MBL production among Gram-negative bacilli is crucial for the optimal treatment of patients and to control the spread of resistance. It also confirms that VIM-2 is by far the most common VIM-type b-lactamase. This isolate was the first and unique P. aeruginosa harbouring this resistance phenotype in our hospital. Moreover, even if this prostatitis corresponded to a nosocomial infection acquired in our hospital, we could not exclude the fact that this patient coming from Saudi Arabia was previously colonized with this strain which was selected by extendedspectrum cephalosporins. To our knowledge, this observation could therefore constitute the first report of the dissemination of VIM-MBL in the Middle East.

The combination of aztreonam and cefozopran against Stenotrophomonas maltophilia.

Aztreonam is suited for combination chemotherapy because it could be a potent Beta-lactamase inhibitor. We designed a study to show the inhibitory activity of aztreonam, using Stenotrophomonas maltophilia, which produces both carbapenemase L1 and penicillinase L2. Aztreonam showed considerable synergy with cefpirome and contributed to a decrease in minimum inhibitory concentrations of cefozopran. In further examinations, the mean viable bacterial counts in cultures treated with aztreonam-cefozopran were 1 log lower than those in cultures treated with cefozopran alone. These results confirm that inhibition of penicillinase L2 occurred. We hope that a combination chemotherapy using aztreonam and cefozopran will be used to prevent the emergence of penicillinase-producers.

Contemporary in vitro synergy rates for aztreonam combined with newer fluoroquinolones and β-lactams tested against gram-negative bacilli

Aztreonam has been commonly used in various combinations to enhance antimicrobial spectrum of co-drugs and produce potential synergistic activity. Although well studied in vitro over 10 years ago, aztreonam combination testing has been poorly documented with newer or commonly used agents against contemporary isolates. All MIC tests (alone or in combination) used in this experiment were reference broth microdilution methods in checkerboard tray designs. Aztreonam was combined with ciprofloxacin, gatifloxacin, levofloxacin, cefepime, ceftazidime and imipenem at clinically relevant concentrations. Interaction categories were defined by established criteria. Forty strains each of Pseudomonas aeruginosa and Enterobacteriaceae (12 species; aztreonam MIC, 1-16 μg/ml) were tested for each antimicrobial combination (480 total determinations). No antagonism or indeterminate interactions were identified. The overall rates of synergy or partial synergy for aztreonam with fluoroquinolone combinations was 63.4% versus P. aeruginosa, greatest for aztreonam with gatifloxacin (67.5%). Interaction categories varied greatly among aztreonam with β-lactam combinations. Aztreonam with ceftazidime or cefepime versus P. aeruginosa had 75.0 - 85.0% partial or complete synergy rates, but aztreonam with imipenem showed dominant indifference (65.0%). In contrast, aztreonam with imipenem was more likely to exhibit synergy (32.5%) when tested against Enterobacteriaceae. Aztreonam, often used as an aminoglycoside substitute in antimicrobial combinations, continues to demonstrate enhanced, but variable drug activity interactions for contemporary antimicrobial combinations when tested against recent (2002) clinical isolates.

In vitro Synergy Studies Using Aztreonam and Fluoroquinolone Combinations against Six Species of Gram-Negative Bacilli

Background: Combination antimicrobial therapy is often necessary to eradicate infections caused by gram-negative bacteria. Methods: To evaluate the potential benefit of aztreonam and fluoroquinolone combination therapy, the activity of aztreonam in combination with ciprofloxacin, gatifloxacin, levofloxacin and moxifloxacin was assessed using checkerboard testing for four clinical isolates of each of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Burkholderia cepacia and Pseudomonas aeruginosa.Results: All aztreonam and fluoroquinolone combinations demonstrated additive activity [fractional inhibitory concentration (FIC) index >0.5–4] or synergy (FIC index ≤0.5) for all 24 isolates tested. Aztreonam plus ciprofloxacin was the most effective combination, demonstrating synergy against 16.7% of isolates (2 P. mirabilis, 1 E. cloacae, 1 B. cepacia). Aztreonam in combination with moxifloxacin was synergistic against 2 isolates (P. mirabilis, E. cloacae), and in combination with gatifloxacin against 1 isolate (E. cloacae). Aztreonam and levofloxacin demonstrated only additive activity. Conclusion: Additive activity was observed for the majority of the aztreonam and fluoroquinolone combinations tested against six species of gram-negative bacilli. Synergy involving aztreonam and fluoroquinolone combinations was less common than additive activity and was isolate dependent. Although in vivo clinical successes have been documented using aztreonam in combination with other agents, confirmation by laboratory techniques requires further investigation.

Involvement of N-acetylmuramyl-L-alanine amidases in cell separation and antibiotic-induced autolysis of Escherichia coli.

N-acetylmuramyl-L-alanine amidases are widely distributed among bacteria. However, in Escherichia coli, only one periplasmic amidase has been described until now, which is suggested to play a role in murein recycling. Here, we report that three amidases, named AmiA, B and C, exist in E. coli and that they are involved in splitting of the murein septum during cell division. Moreover, the amidases were shown to act as powerful autolytic enzymes in the presence of antibiotics. Deletion mutants in amiA, B and C were growing in long chains of unseparated cells and displayed a tolerant response to the normally lytic combination of aztreonam and bulgecin. Isolated murein sacculi of these chain-forming mutants showed rings of thickened murein at the site of blocked septation. In vitro, these murein ring structures were digested more slowly by muramidases than the surrounding murein. In contrast, when treated with the amidase AmiC or the endopeptidase MepA, the rings disappeared, and gaps developed at these sites in the murein sacculi. These results are taken as evidence that highly stressed murein cross-bridges are concentrated at the site of blocked cell division, which, when cleaved, result in cracking of the sacculus at this site. As amidase deletion mutants accumulate trimeric and tetrameric cross-links in their murein, it is suggested that these structures mark the division site before cleavage of the septum.

Effects of Aztreonam in Combination with Antipseudomonal Antibiotics against Pseudomonas aeruginosa Isolated from Patients with Chronic or Recurrent Lower Respiratory Tract Infection

AbstractThe antipseudomonal activity of aztreonam combined with other antibiotics aas examined in vitro to suggest effective therapeutic combinations for the treatment of respiratory tract infections due to Pseudomonas aeruginosa. Twenty-five P. aeruginosa strains were newly isolated from patients with chronic or recurrent lower respiratory tract infection. The susceptibility of these strains to aztreonam alone and to aztreonam combined with ceftazidime, cefclidin, isepamicin and imipenem was measured using the checkerboard method. The observed MICs suggested that aztreonam alone was not very potent against P. aeruginosa associated with chronic or recurrent lower respiratory infection, but that cefclidin had strong antipseudomonal activity. The fractionary inhibitory concentration index showed synergy in 60% of the P. aeruginosa clinical isolates with aztreonam plus isepamicin, and antagonism in approximately 16% of strains with aztreonam plus imipenem. When combined with isepamcin, aztreonam may have potent activity against pseudomonal lower respiratory tract infections.

Evaluation of antibiotic-induced nephrotoxicity in preterm neonates by determining urinary α1-microglobulin

alpha 1-Microglobulin (alpha 1-m, protein HC), a relatively low molecular weight protein of about 31,000 daltons, was measured in urine of three groups of 34 preterm neonates: group A consisted of 9 healthy preterm neonates; groups B (n = 13) and C (n = 12) consisted of preterm neonates with suspected or confirmed bacterial infections. Immediately after birth, all group B neonates were treated with ampicillin and aztreonam in combination, and all group C neonates were treated with oxacillin and amikacin in combination. To optimize amikacin administration, computerized individually tailored doses were administered. Urine samples were obtained from a short collection in sterile bags on the 1st, 4th, and 7th day after delivery in all infants. Urinary alpha 1-m concentrations were measured by a turbidimetric method (latex agglutination photometric immunoassay) and results were expressed as a ratio to urinary creatinine. In group A, urinary alpha 1-m concentrations were stable after birth. In group C, alpha 1-m excretion increased immediately within the 1st day of treatment, and over the 1st week of life urinary alpha 1-m levels were significantly higher than in group A (P = 0.033). These data support the conclusion that amikacin administration was the most important factor inducing renal tubular dysfunction in the neonates of group C.

Pharmacodynamics of once-daily amikacin in various combinations with cefepime, aztreonam, and ceftazidime against Pseudomonas aeruginosa in an in vitro infection model

The pharmacodynamics of once-daily amikacin administered as monotherapy and in combination with aztreonam, ceftazidime, and cefepime against Pseudomonas aeruginosa ATCC 27853 and clinical isolate 16690 (moderately susceptible to ceftazidime) were investigated with an in vitro model of infection over a 24-h period. Monotherapy with aztreonam, ceftazidime, and cefepime and combinations of aztreonam with cefepime or ceftazidime were also studied. MICs and MBCs were determined for viable organisms at 24 h to test for the development of resistance. Once-daily amikacin demonstrated killing activity over the initial 8 h superior to those of all other drugs administered as monotherapy against both strains tested (P < 0.01). Regrowth by 24 h was greatest for the amikacin regimen (P < 0.01) but was apparent for all monotherapy regimens against both strains. No changes in susceptibilities were observed. All combination therapies containing once-daily amikacin achieved 99.9% reductions in log10 CFU/ml by 2.0 h against both strains, with no regrowth of organisms at 24 h. Aztreonam-cefepime and -ceftazidime combinations required approximately 5 to 6 h to achieve a 99.9% reduction in log10 CFU/ml. Although there was no difference in time to the 99.9% kill between the aztreonam-cefepime and -ceftazidime regimens against either strain, the killing activity of these combinations was significantly less than those of regimens containing once-daily amikacin (P < 0.01). Minor differences in the initial susceptibilities of beta-lactams and the monobactam aztreonam against P. aeruginosa may not be important for therapeutic outcomes when used in combination with single-daily aminoglycoside therapy.

Clinical Use Of Aztreonam in a Psychogeriatric Population

Aztreonam is a safe, well-tolerated antibiotic with a good response in psychogeriatric patients. The combination of aztreonam with flucloxacillin is an acceptable first-choice treatment for severe infections in psychogeriatric patients.

Infections in Patients in Intensive Care Units: Can the Combination of a Monobactam and a Penicillin Replace the Classic Combination of a β-Lactam Agent and an Aminoglycoside?

An open, comparative, randomized study was performed in two medical intensive care units to compare the efficacy of the combination of aztreonam and either cloxacillin or oxacillin [(cl)oxacillin] with that of the combination of tobramycin and a cephalosporin. Of the 92 patients who were included in the study, 76 were evaluable. All patients suffered from severe, mostly pulmonary, infections and received ventilatory support. The aztreonam combination yielded an 80% rate of clinical cure; mortality was 15%. Use of the aminoglycoside combination resulted in a 51% rate of clinical cure; mortality was 23%. The difference in cure rate between the two combinations was statistically significant. Adverse effects were negligible in patients who received the aztreonam combination, and superinfection was seen in only 2%. Of the patients who received the aminoglycoside combination, 20% developed a superinfection and 11% developed a new renal insufficiency. Therefore, the combination of aztreonam and (cl)oxacillin is a valuable alternative to the combination of an aminoglycoside and a cephalosporin.