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Biomedical subjects

M R Moody

Publications and source records attributed to M R Moody.

At least 37 records · Page 2Linked to original sources
PubMed1985

Potential of imipenem as single-agent empiric antibiotic therapy of febrile neutropenic patients with cancer.

Infection remains a major cause of morbidity and mortality for the patient with cancer who experiences episodes of severe granulocytopenia. The search continues for new antimicrobial agents with improved efficacy and lower incidence of toxicity. Imipenem is a new carbapenem antibiotic which possesses a broad antibacterial spectrum with excellent activity against Pseudomonas aeruginosa and the other commonly recovered enteric gram-negative bacilli that infect the granulocytopenic patient with cancer. The combination of imipenem plus an aminoglycoside has shown in vitro synergy against P. aeruginosa and Staphylococcus aureus whereas the combination of imipenem plus piperacillin or the extended spectrum cephalosporins have frequently shown antagonism when tested against P. aeruginosa and Serratia marcescens. The use of a P. aeruginosa-infected neutropenic rat model has provided an in vivo system to evaluate the activity of new antibiotics or antibiotic combinations. Monotherapy with imipenem is as effective in this model as any of the currently available synergistic antibiotic combinations. This degree of activity has not been found with other broad-spectrum antibiotics when used alone. Imipenem provides serum bactericidal activity well above a 1:8 dilution for the four most commonly isolated pathogens: P. aeruginosa, Escherichia coli, Klebsiella species, and S. aureus. In addition, imipenem's post-antibiotic effect against P. aeruginosa may be pertinent. Imipenem is a unique antibiotic, with properties that make it well suited for study as monotherapy for fever and suspected infection in granulocytopenic patients with cancer. A prospective randomized, double-blind study comparing imipenem with a control regimen of piperacillin plus amikacin as empiric antibiotic therapy of febrile granulocytopenic patients with cancer is currently underway at the University of Maryland Cancer Center.

Agranulocytosis↗
PubMed1985

Comparative pharmacokinetics and serum bactericidal activity of mezlocillin, ticarcillin and piperacillin, with and without gentamicin.

We compared the serum levels, pharmacokinetics and serum bactericidal activity after intravenous infusions of 5 g of each of three anti-pseudomonal penicillins--ticarcillin, mezlocillin and piperacillin alone and in combination with 80 mg gentamicin in normal volunteers. Gentamicin levels were significantly lower when administered with ticarcillin than when administered with mezlocillin or piperacillin. Serum levels of ticarcillin and piperacillin immediately after the infusion were similar (approximately 450 mg/l) and were higher than mezlocillin at 350 mg/l, but by 6 h, levels of all three penicillins were less than 10 mg/l. Overall, the geometric mean bactericidal titres produced in the serum against organisms which commonly infect cancer patients with granulocytopenia were highest with the piperacillin-gentamicin combination. However, except for the mezlocillin-gentamicin combination against Pseudomonas aeruginosa, serum bactericidal titres of all three penicillin-gentamicin regimes were greater than 1:8 at zero and 2 h after the infusion against the organisms tested. It is unlikely that these differences in the three penicillin-gentamicin combinations will be apparent in the outcome of clinical trials for empiric therapy of fever in the cancer patient with granulocytopenia.

Adult↗
PubMed1984

Persistent isolation of an unusual Pseudomonas species from a phenolic disinfectant system.

A well-characterized unusual Pseudomonas species contaminated the piped disinfectant system of a newly-opened laminar air flow intensive care facility. This organism was frequently isolated (10(4)-10(6) cfu/ml) from phenolic diluted 1:256 in the system, and could also be recovered (0.01-0.2 cfu/ml) from undiluted phenolic. During the 20-month period when this unusual Pseudomonas was present, none of the severely compromised, granulocytopenic oncology patients treated in the intensive care facility were either colonized or infected with this Pseudomonas sp. Eradication of the organism from the system proved difficult and was accomplished by removing a contaminated reservoir of diluted phenolic disinfectant followed by transient cleansing of the system with very high concentrations (84,000 ppm) of chlorine. This experience demonstrates that phenolics should be added to the list of disinfectants which can harbor Pseudomonas spp. in the clinical setting.

Air Microbiology↗
PubMed1984

Comparison of the pharmacokinetics of ceftazidime and moxalactam and their microbiological correlates in volunteers.

We compared ceftazidime with moxalactam, a commonly utilized, currently available drug. The microbiological activities of ceftazidime and moxalactam were studied. In addition, single-dose pharmacokinetics and serum bactericidal activity 1 and 6 h after a 2.0-g, 30-min infusion of each drug were determined in a crossover study in human volunteers. In vitro, both drugs had MICs for 90% of the isolates of less than 1.0 microgram/ml against the common members of the family Enterobacteriaceae and of 8.0 micrograms/ml against Staphylococcus aureus. Against Pseudomonas aeruginosa ceftazidime was more active than moxalactam, the respective MICs for 90% of the isolates being 8 and 128 micrograms/ml. Mean half-lives were 1.75 (+/- 0.21) h for ceftazidime and 2.5 (+/- 0.38) h for moxalactam. The serum bactericidal titers for both compounds against Escherichia coli and Klebsiella pneumoniae were high. Titers against S. aureus 6 h after infusion were negative. The mean (geometric) serum bactericidal titer of ceftazidime against 31 strains of P. aeruginosa (1:44) was higher than that of moxalactam (1:3.4).

Adolescent↗
PubMed1982

Empiric antibiotic therapy for suspected infection in granulocytopenic cancer patients: a comparison between the combination of moxalactam plus amikacin and ticarcillin plus amikacin.

Moxalactam is a new cephalosporin with a broad spectrum of activity which includes Pseudomonas aeruginosa in addition to Klebsiella species Escherichia coli, and Staphylococcus aureus. Moxalactam was combined with amikacin (M + A) compared to ticarcillin plus amikacin (T + A) in a prospective, randomized double-blind trial of empiric therapy for febrile episodes among granulocytopenic cancer patients. One hundred and ninety-one epidoses were evaluated; T + A, 93 episodes and M + A, 98 episodes. Median granulocyte count of initiation of therapy was less than 100/microliters. Overall response rates were good. In the T + A group, 21 of 29 (72 percent) microbiologically documented infections, including seven of 14 (50 percent) bacteremias, and 24 of 27 (89 percent) clinically documented infections improved. In the M + A group, 20 of 28 (71 percent) microbiologically documented infections, including 11 of 18 (61 percent) bacteremias, and 25 of 25 (96 percent) clinically documented infections resolved. Adverse effects were minimal and equivalent in both groups. Hypokalemia (decrease in serum potassium of greater than 11 mEq/liter from baseline) occurred in 14 of the 93 episodes in the T + A group and in 10 of the 98 episodes in the M + A group with decline in mean serum potassium level of 0.5 and 0.4 mEq/liter respectively. Nephrotoxicity (increase in serum creatinine greater than 0.04 mg/dl) occurred in only one patient in the T + A group and in two patients in the M + A group. Moxalactam plus amikacin has a broader in vitro spectrum, is as effective, and is no more toxic than ticarcillin plus amikacin as empiric therapy for febrile granulocytopenic cancer patients.

Adolescent↗
PubMed1981

The emergence of coryneform bacteria as a cause of nosocomial infections in compromised hosts.

Corynebacterium species that are normally abundant on the skin and mucous membranes rarely cause infections and are susceptible to most antibiotics. The report in 1976 of four cases of sepsis at the National Institutes of Health caused by a hitherto undescribed corynebacterium that is highly antibiotic resistant, but uniformly susceptible to vancomycin, alerted the medically oriented scientific community to the emergence of these organisms as a possible new cause of nosocomial infections. Although we have always performed antibiotic susceptibility tests on all microorganisms recovered from normally sterile body fluids, our first recovery of these organisms was in August 1977. Since then we have recovered 52 such strains from 39 patients, most frequently from the rectum, followed by the groin, blood, lesions and urine in order of predominance. Characterization by API 50 L strips revealed that most, but not all strains resemble the JK group of Riley et al. [1]. Cell wall studies and DNA base ratios further confirmed their status as corynebacteria. Hospital acquisition has been proved; cross infection between patients is the most likely mode of spread. Their recognition is necessary for optimal preventive and therapeutic care of patients with compromised host defenses.

Agranulocytosis↗
PubMed1980

Distribution of Serratia marcescens serotypes in cancer patients.

A study of 1314 patients with malignancies was made to determine the prevalence of Serratia marcescens in surveillance, diagnostic, and environmental cultures. Sera obtained from a commercial source were used to determine serotypic distributions of the S. marcescens strains isolated during a 51-month period. S. marcescens was isolated from 19% of patients with haematological neoplasms, from 5% of patients with lymphoma, and from 6% of those with solid tumours. Among carriers, rectal cultures were the commonest source in patients with lymphoma (32%); rectal and gingival cultures in patients with leukaemia (43% and 39%, respectively), and gingival cultures in patients with solid tumours (30%). Bacteraemias (.07%) were infrequent sources. Although seldom isolated from environmental or food samples, S. marcescens may occasionally be abundant in fresh fruit and vegetables. Serotyping of 220 strains of S. marcescens demonstrated 38 distinct antigenic types. The predominant serotype, O14:H12, was present in the upper respiratory tract of half of the persons who carried this serotype. Serotyping is a readily reproducible method of subspeciating S. marcescens; it can be satisfactorily used as an epidemiological tool.

Bacteriuria↗
PubMed1980

Phase variation in the genus Serratia.

During an investigation of the serotypes of Serratia marcescens present in a cancer centre, it was found that 8.7% of 241 strains had more than one H antigen. There were 19 diphasic and two triphasic strains. Antigen H1 was a component of the phases in the approximately half of the strains with multiple phases. This is the first report of such phases in the genus Serratia.

Antigens, Bacterial↗
PubMed1980

In vitro activities of miconazole, miconazole nitrate, and ketoconazole alone and combined with rifampin against Candida spp. and Torulopsis glabrata recovered from cancer patients.

A total of 440 fresh clinical isolates of yeasts from cancer patients were tested by an agar dilution technique against miconazole, miconazole nitrate, and ketoconazole individually and combined with 5 micrograms of rifampin per ml. Most strains of Candida albicans were susceptible to 0.5 microgram or less of the imidazoles per ml. Candida tropicalis required 2 to 4 micrograms of miconazole and its nitrate base per ml for inhibition and was resistant to ketoconazole. The 100% minimal inhibitory concentration of the imidazoles for Candida krusei was 1 microgram/ml. Susceptibility to 4 micrograms of miconazole and miconazole nitrate per ml occurred in 73 and 87% of Torulopsis glabrata strains, respectively, and none was susceptible to ketoconazole. Miconazole was most effective against the Candida spp., whereas its nitrate base was most active against T. glabrata. Synergy was observed when rifampin was combined with miconazole and miconazole nitrate but was not observed when rifampin was combined with ketoconazole. Synergy occurred most frequently when rifampin was combined with miconazole nitrate.

Antifungal Agents↗
PubMed1980

Potential of mezlocillin as empiric single-agent therapy in febrile granulocytopenic cancer patients.

Mezlocillin was used as an initial empiric antibiotic therapy for febrile (> 101 degrees F, ca. 38.33 degrees C) granulocytopenic (< 1,000/microliter) cancer patients. Patients known to be colonized with an organism resistant to 100 micrograms of mezlocillin per mol were excluded. The initial 25 cases (23 patients) received intravenous mezlocillin, 260 mg per kg per day in six divided doses; the mean 1-h-postinfusion serum level was 69 micrograms/ml. Because of the low serum level, the next 25 cases (22 patients) received 450 mg/kg per day, also in six divided doses, resulting in a mean 1-h-postinfusion serum level of 161 micrograms/ml. Both dosage regimens provided similar efficacy. Combined results show that 11 of 21 microbiologically documented infections and 7 of 13 clinically documented infections improved. Instances of bacteremia (number of cases in parentheses) were caused by Pseudomonas aeruginosa (two), Staphylococcus epidermidis (two), Clostridia perfringens (one), and Bacillus species (one); only one case improved. A rise in granulocyte count to > 500/microliters, a serum bactericidal activity of greater than or equal to 1:8 against the infecting pathogen, or both were indicators of a good therapeutic response. Despite exclusion of patients known to be previously colonized with mezlocillin-resistant organisms, 7 of 23 pathogens required a minimal concentration of greater than or equal to 100 micrograms of mezlocillin per ml for inhibition. In addition, surveillance cultures from 18 cases showed resistant organisms colonizing the gingiva, rectum, or both. Side effects of mezlocillin were minimal and included pseudoproteinuria, asymptomatic transient rise in bilirubin, and easily reversible kypokalemia. Mezlocillin, a new semisynthetic penicillin with little toxicity, was found to be inadequate as a single-agent empiric antibiotic therapy for febrile, granulocytopenic cancer patients.

Adult↗
PubMed1978

Evaluation of a multitest system for identification of saccharolytic pseudomonads.

The API-20 Enteric Strip has been proposed to have the capacity to differentiate the nonfermentative gram-negative bacilli. This multitest strip serves as the basis of an evolving system, which first provided a Register, then a Selector, and more recently a computer Index. Twenty-three strains of Pseudomonas aeruginosa and P. putida, 21 of P. fluorescens, 27 of P. maltophilia, and 33 of P. cepacia were investigated by duplicate test runs to determine reproducibility. The results were then evaluated at each of the three stages to determine accuracy of identification and the effect of the system evolution on the identification rate. Seventy-one of the 127 pseudomonads gave reproducible results in the multitest strips. Approximately half of them were correctly grouped or speciated by the Register, whereas 80 to 83% were similarly identified by both the Selector and Index. Of the clinically important pseudomonads, 61 to 65% of P. aeruginosa and 93% of P. maltophilia strains were correctly speciated; neither P. putida nor P. fluorescens strains were speciated, although most were correctly grouped. P. cepacia was speciated by the Index with only 55 to 58% accuracy. Although the present stage of the evolving system offers improvement over the Register, further modifications are needed to eliminate identification problems and to increase speciation.

Bacteriological Techniques↗
PubMed1978

Effect of two cancer chemotherapeutic agents on the antibacterial activity of three antimicrobial agents.

Cancer chemotherapeutic agents and antibacterial antibiotics are often given concomitantly. Daunorubicin, cytosine arabinoside, and three antibiotics (gentamicin, amikacin, and ticarcillin) were tested individually and in combinations to determine their antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. These cytotoxic agents are commonly employed in the therapy of acute nonlymphocytic leukemia for remission induction therapy, and these antimicrobial agents are used in infection therapy. The maximum concentrations of the two cytotoxic drugs were chosen to be twice the known peak plasma levels of commonly employed dosage schedules. Neither of the cancer chemotherapeutic agents, alone or in combination, demonstrated bactericidal activity at the levels tested. However, in the presence of these agents, the antimicrobial activity of gentamicin and amikacin, although not that of ticarcillin, was depressed for 11 of 15 K. pneumoniae strains and 8 of 15 P. aeruginosa strains, but for none of the strains of E. coli. This level of decreased activity occasionally resulted in a minimal inhibitory concentration of the tested aminoglycoside well above the standard serum levels. Daunorubicin was more likely to antagonize gentamicin than was cytosine arabinoside.

Amikacin↗
PubMed1978

Role of nonagglutinating antibody in the protracted immunity of vaccinated mice to Pseudomonas aeruginosa infection.

Effective immunization against infection with Pseudomonas aeruginosa is difficult to evaluate because agglutinin levels decline rapidly. Because fractionation of hyperimmune sera often yields more specific antibody than can be accounted for by direct agglutination tests, an immunoglobulin-specific assay based on antiglobulin augmentation was used to characterize antibody responses of C3H/HeJ mice vaccinated with P. aeruginosa type 2 lipopolysaccharide. Nonagglutinating antibodies, initially detected at 2 weeks post-primary vaccination, were predominantly immunoglobulin G after 5 weeks, and they remained elevated at levels usually 32-fold higher than the direct titer throughout the 4-month study period. The sequential production of immunoglobulin M, then immunoglobulin G, followed that found in orthodox immunological responses. Sera that contained nonagglutinating antibodies but not direct agglutinins (14 to 16 weeks) enhanced phagocytosis of P. aeruginosa type 2 by macrophages from unimmunized mice and passively immunized mice against lethal challenge doses; bactericidal activity of these sera was not demonstrated in the presence or absence of complement. When challenged with 1, 10, and 100 50% lethal doses at 16 weeks, survival rates of actively immunized mice were significantly higher than those of unvaccinated mice (P < 0.001). Thus, at a time when no direct agglutinins were detectable, the augmented system detected nonagglutinating antibodies that could confer protracted resistance in vaccinated mice to pseudomonas infection.

Agglutinins↗
PubMed1975

In vitro susceptibility of Pseudomanas cepacia and Pseudomonas maltophilia to trimethoprim and trimethoprim-sulfamethoxazole.

Our earlier studies had shown that the two pseudomonads, Pseudomonas cepacia and Pseudomonas maltophilia, were organisms that were highly resistant to most antibiotics. The present study was undertaken to determine the susceptibility of these bacteria to trimethoprim and the trimethoprim-sulfamethoxazole combination which has been used with apparent success in treating infections caused by these pseudomonads. All 51 strains of P. cepacia were inhibited by 2 mug or less of trimethoprim per ml, whereas all 45 of the P. maltophilia were resistant to greater than 32 mug/ml. When the P. maltophilia was tested against trimethoprim-sulfamethoxazole, two strains were resistant and one only moderately resistant, but all other strains were susceptible. All P. cepacia strains were also susceptible with an average zone of inhibition significantly larger than for P. maltophilia (P < 0.005). These in vitro studies support recent case study reports of successful therapy using the trimethoprim-sulfamethoxazole combination.

Drug Combinations↗