Clinical Efficacy of Moxalactam with Emphasis on Infections Due to Multidrug-Resistant Organisms in Patients with Renal Insufficiency

Trager, Gary M.; Panwalker, Anand P.; Malow, James; Porembski, Priscilla E.; Ramírez, Claudio; Zar, Fred A.

doi:10.1159/000237993

Cited by 11 publications

(2 citation statements)

References 9 publications

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“…Many were optimistic that this relatively safe drug might prove useful as a single agent for infections previously requiring aminoglycoside therapy. Early clinical trials showed moxalactam to be safe and effective for a wide spectrum of bacterial infections (3,(19)(20)(21) with a final volume of 3 ml and a final inoculum of 105 colony-forming units (CFU) per ml. The minimal inhibitory concentration (MIC) was defined as the lowest antibiotic concentration preventing macroscopically detectable growth after 18 h of incubation at 35°C in air.…”

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confidence: 99%

Emergence of resistance to beta-lactam and aminoglycoside antibiotics during moxalactam therapy of Pseudomonas aeruginosa infections

Preheim¹,

Penn²,

Sanders³

et al. 1982

Antimicrob Agents Chemother

106

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In four patients with Pseudomonas aeruginosa infections, the infecting strain developed resistance to moxalactam during therapy with this drug. In addition, P. aeruginosa isolates from two of these four patients showed increased resistance to aminoglycosides. Isolates from a third patient acquired cross-resistance to other antipseudomonal ,3-lactams. with a final volume of 3 ml and a final inoculum of 105 colony-forming units (CFU) per ml. The minimal inhibitory concentration (MIC) was defined as the lowest antibiotic concentration preventing macroscopically detectable growth after 18 h of incubation at 35°C in air. Subcultures (0.01 ml) were made of all clear tubes to drug-free agar, and the minimal bactericidal concentration (MBC) was defined as the lowest concentration preventing growth upon subculture. This represented a 99.9o kill of the original inoculum (12). MICs or MBCs for posttherapy isolates were considered increased above results obtained with pretherapy isolates if they differed at least fourfold. Tests on pre-and posttherapy isolates were performed simultaneously. Results of susceptibility tests were interpreted according to criteria pubished by the National Committee for Clinical Laboratory Standards (10). For moxalactam, an organism was considered (i) resistant if the MIC was 264 ,ug/ml and (ii) susceptible if the MIC was c32 pLg/ml. ,B-Lactamase assays were performed by a spectrophotometric test as described previously (16). Enzymes were induced by growing the strains overnight on cefoxitin agar (16). Strains resistant to aminoglycosides were tested for inactivating enzymes by R. Hare (Schering Corp., Bloomfield, N.J.).Agarose gel electrophoress. To compare the plasmid profiles of the isolates, cultures were lysed by the method of Meyers et al.

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mentioning

confidence: 99%

Emergence of resistance to beta-lactam and aminoglycoside antibiotics during moxalactam therapy of Pseudomonas aeruginosa infections

Preheim¹,

Penn²,

Sanders³

et al. 1982

Antimicrob Agents Chemother

106

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“…The poor drainage associated with bronchial obstruction added to the difficulty in treatment, but the susceptibility to ceftriaxone decreased eightfold while the patient was on therapy (Table 1). Although not studied in this patient, selection of resistant organisms from an original heterosusceptible population has been described in similar situations with other new 3-lactam antibiotics (8,15). …”

Section: Resultsmentioning

confidence: 73%

Ceftriaxone (Ro 13-9904) therapy of serious infection

Bradsher¹

1982

Antimicrob Agents Chemother

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Ceftriaxone (Ro 13-9904), a newly developed cephalosporin with a long halflife, was evaluated for efficacy and safety in 19 patients with serious infections. Underlying illnesses were present in 16 patients. Ceftriaxone was given intravenously every 12 h. Infections treated included gram-negative bacillary pneumonias (two cases), staphylococcal and streptococcal soft tissue-skeletal infections (six cases), spontaneous peritonitis (two cases), and complicated urinary tract infections (nine cases). Bacteremia was present in three patients. Microbiological and clinical cures were achieved in all but one case, although three patients with urinary infection had recurrences 6 weeks posttherapy. The only failure occurred in a patient with pneumonia who had a Pseudomonas aeruginosa isolated from sputum with an initial minimal inhibitory concentration of 4 ,uglml, but after 9 days of therapy, a repeat isolate had a minimal inhibitory concentration of 32 ,ug/ml. The minimal inhibitory concentrations for the other isolates ranged from <0.6 to 8.0 ,ug/ml. The mean peak plasma level of ceftriaxone was 99.9 ,ug/ml, whereas ceftriaxone levels obtained 12 h after a dose had a mean of 37.3 ,ug/ml. The only side effects noted were drug fever in one patient, phlebitis in two patients, and thrombocytosis in four patients.Cephalosporin antibiotics are widely used to treat serious infections because of the spectrum of activity and the relative safety compared with other types of antibiotics. Several newly developed cephalosporins have increased potency against Enterobacteriaceae while maintaining activity against streptococci and staphylococci. Ceftriaxone (Ro 13-9904) is a 2-aminothiazolyl methoxyimino cephalosporin which inhibits most gram-negative enteric bacilli and streptococci at concentrations of less than 1 ,ug/ml (3,5,12). It has a potential advantage over other recently discovered P-lactam antibiotics because of a contrast in pharmacokinetics. Ceftriaxone has a serum half-life of 8 h compared with 1 to 3 h for cefotaxime, cefoperazone, moxalactam, and other investigative third-generation cephalosporins (10). This prolonged serum half-life apparently is related to a high degree of protein binding and a different excretion pattern for ceftriaxone compared with the cephalosporins listed above (11,16). In an open trial, the safety and clinical and bacteriological efficacy of ceftriaxone therapy of serious bacterial infection at a dosage of 1.0 g twice a day were evaluated.(

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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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Clinical Efficacy of Moxalactam with Emphasis on Infections Due to Multidrug-Resistant Organisms in Patients with Renal Insufficiency

Cited by 11 publications

References 9 publications

Emergence of resistance to beta-lactam and aminoglycoside antibiotics during moxalactam therapy of Pseudomonas aeruginosa infections

Emergence of resistance to beta-lactam and aminoglycoside antibiotics during moxalactam therapy of Pseudomonas aeruginosa infections

Ceftriaxone (Ro 13-9904) therapy of serious infection

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

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