Serum Bactericidal Activity of Moxalactam and Cefotaxime With and Without Tobramycin Against
            <i>Pseudomonas aeruginosa</i>
            and
            <i>Staphylococcus aureus</i>

Lagast, Hjalmar; Zinner, Stephen H.; Klastersky, Jean

doi:10.1128/aac.20.4.539

Cited by 10 publications

(4 citation statements)

References 15 publications

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“…At 6 h, the combination was significantly more effective against all strains than was cefotaxime alone. Our data are comparable with those of other investigators who have shown a limited increase in the bactericidal activity of cefotaxime when aminoglycosides have been added (4 …”

supporting

confidence: 82%

“…It is generally agreed upon that a bactericidal activity in serum of >1:8 correlates with the clinical effectiveness of antibiotics (3, 5a, 11), but in a recent review Wolfson and Swartz (12) have concluded that convincing proof of the utility of the bactericidal activity test in serum in the management of infective endocarditis is lacking. Lagast and co-workers studied the bactericidal activity in serum of cefotaxime alone and in association with tobramycin against clinical strains of Pseudomonas aeruginosa and Staphylococcus aureus (4). They observed increased activity of cefotaxime against both strains when used in combination with tobramycin.…”

mentioning

confidence: 99%

“…sequence: before drug was administered and at 10, 30, 45, and 60 min and 1.5, 2, 2.5, 3,4,6,8,10, and 24 h after antibiotic administration. Urine was collected on both study days immediately before injection(s) and at intervals between 0 and 2, 2 and 4, 4 and 8, and 8 and 24 h after antibiotic(s) administration.…”

mentioning

confidence: 99%

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Comparative study of serum bactericidal activity of cefotaxime alone or in combination with tobramycin

Bergeron¹,

LeBel²,

Charest³

et al. 1986

Antimicrob Agents Chemother

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The objectives of this study were to investigate the bactericidal activity in serum of cefotaxime alone or in combination with tobramycin against clinical strains and to determine the influence of tobramycin on the pharmacokinetics of cefotaxime. The The bactericidal activity test in serum has been recommended to monitor antimicrobial therapy in patients with serious infections. It is generally agreed upon that a bactericidal activity in serum of >1:8 correlates with the clinical effectiveness of antibiotics (3, 5a, 11), but in a recent review Wolfson and Swartz (12) have concluded that convincing proof of the utility of the bactericidal activity test in serum in the management of infective endocarditis is lacking. Lagast and co-workers studied the bactericidal activity in serum of cefotaxime alone and in association with tobramycin against clinical strains of Pseudomonas aeruginosa and Staphylococcus aureus (4). They observed increased activity of cefotaxime against both strains when used in combination with tobramycin. In this study we extend the investigation of the bactericidal activity in serum of cefotaxime alone or in combination with tobramycin to clinical isolates of Klebsiella oxytoca, Enterobacter aerogenes, Serratia marcescens, Pseudomonas cepacia, and Listeria monocytogenes.(This paper was presented at the 14th International Congress of Chemotherapy, Kyoto, Japan, in June 1985.) Twelve healthy subjects (six females, six males) between the ages of 20 and 24 years (mean, 21.7 years) gave written informed consent to participate in the study. The protocol was approved by the Centre Hospitalier de l'Universite Laval Human Research Review and PharmacologyTherapeutic Committees. The mean weight of the subjects was 64.4 kg (range, 57.0 to 84.5 kg). Based on creatinine and blood urea nitrogen values in serum, these young volunteers had normal renal function. The subjects received 1 g of cefotaxime and, 1 week later, 1 g of cefotaxime with 80 mg of tobramycin. Both antibiotics were diluted in 50 ml of 0.9% sodium chloride and given intravenously over 5 min. When both drugs were given simultaneously, they were never mixed in vitro but were administered at separate venipuncture sites. Tobramycin inactivation by cefotaxime is minimal, even in vitro (2).Blood samples were drawn from a catheter (contralateral to the one used for cefotaxime infusion) by the following * Corresponding author. sequence: before drug was administered and at 10, 30, 45, and 60 min and 1.5, 2, 2.5, 3,4,6,8,10, and 24 h after antibiotic administration. Urine was collected on both study days immediately before injection(s) and at intervals between 0 and 2, 2 and 4, 4 and 8, and 8 and 24 h after antibiotic(s) administration. Each urine sample was stored at -20°C until it was assayed.Serum and urine samples were analyzed in triplicate for cefotaxime by the high-pressure liquid chromatographic procedure described previously (5); however, the following modifications were made. The serum (0.5 ml) sample preparation involved protein precipita...

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supporting

confidence: 82%

mentioning

confidence: 99%

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Comparative study of serum bactericidal activity of cefotaxime alone or in combination with tobramycin

Bergeron¹,

LeBel²,

Charest³

et al. 1986

Antimicrob Agents Chemother

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“…The bactericidal activity of moxalactam is generally reported as being equivalent to its inhibitory activity against P. aeruginosa (5,6,8,11,16). This assessment has, with a single exception (18), been based on the results of microdilution test procedures with inoculum sizes and subculture volumes which have been insufficient for an accurate determination of 99.9% killing (2,19).…”

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confidence: 99%

Bactericidal and synergistic activity of moxalactam alone and in combination with gentamicin against Pseudomonas aeruginosa

Yu¹,

Edson²,

Washington³

et al. 1983

Antimicrob Agents Chemother

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The bactericidal activity of moxalactam, alone and in combination with gentamicin, was studied with macrobroth two-dimensional checkerboard and killing curve techniques against gentamicin-resistant and -susceptible strains of Pseudomonas aeruginosa. Moxalactam was bactericidal at concentrations equal to or at least two to four times its inhibitory concentrations. Synergy at clinically applicable concentrations of moxalactam and gentamicin occurred with 6 of 14 gentamicin-resistant strains and 4 of 4 gentamicin-susceptible strains by the checkerboard technique and with 7 of 14 gentamicin-resistant strains by the killing curve technique. Synergy between moxalactam and gentamicin against gentamicin-resistant strains of P. aeruginosa is unpredictable and strain- and method-dependent.

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A Comparative Evaluation of Moxalactam: Antimicrobial Activity, Pharmacokinetics, Adverse Reactions, and Clinical Efficacy

Fitzpatrick

Standiford

1982

Pharmacotherapy

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Although moxalactam is not, technically speaking, a cephalosporin it is chemically and microbiologically so closely related to those compounds that it can be viewed as a member of the cephalosporin family. Moxalactam has a spectrum of activity that includes both gram positive and gram negative bacteria. Its gram positive activity is less than earlier cephalosporins, but its activity against the Enterobacteriaceae is similar to that of the aminoglycoside family of antibiotics in most comparative studies. Although moxalactam is considerably less active against gram positive bacteria than cefotaxime, another third generation cephalosporin, its higher and more prolonged serum levels probably offset this disadvantage. Compared to cefoperazone, the stability of moxalactam to many types of beta lactamases produced by gram negative bacteria may be advantageous in the therapy of infections caused by hospital-acquired pathogens. Clinical studies suggest that moxalactam can be used for empiric therapy of suspected gram negative infections when Pseudomonas and other non-fermentative bacteria, such as Acinetobacter, are not suspected. Impressive improvements in the survival of patients with gram negative enteric bacillary meningitis have been reported. Although moxalactam, cefotaxime, and cefoperazone have activity against Pseudomonas aeruginosa, none of these antibiotics should be used alone as therapy for suspected or proven severe systemic infections caused by this pathogen. Cost is a major problem with all of the new cephalosporin-like antibiotics. While this high cost may be partially balanced by the use of a single agent compared to an antibiotic combination for therapy in some situations, these antibiotics are not cost effective for prophylactic use. Superinfection with fungi, such as Candida, and Streptococcus faecalis have occurred, and toxicities, such as bleeding due to vitamin K deficiency and disulfuram-like reactions, have also been reported. Reports of resistance to moxalactam and the other third generation cephalosporins are of major concern and indicate the need to closely monitor antibiotic susceptibility patterns of hospital acquired organisms if these antibiotics are to be used for empiric therapy of suspected gram negative non-pseudomonas sepsis.

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Serum Bactericidal Activity of Moxalactam and Cefotaxime With and Without Tobramycin Against Pseudomonas aeruginosa and Staphylococcus aureus

Cited by 10 publications

References 15 publications

Comparative study of serum bactericidal activity of cefotaxime alone or in combination with tobramycin

Comparative study of serum bactericidal activity of cefotaxime alone or in combination with tobramycin

Bactericidal and synergistic activity of moxalactam alone and in combination with gentamicin against Pseudomonas aeruginosa

A Comparative Evaluation of Moxalactam: Antimicrobial Activity, Pharmacokinetics, Adverse Reactions, and Clinical Efficacy

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