Marcia R. Moody

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.

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.

In Vitro Susceptibility of Pseudomonas 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 μg or less of trimethoprim per ml, whereas all 45 of the P. maltophilia were resistant to greater than 32 μg/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.

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.

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.

Levinea, a New Genus of the Family Enterobacteriaceae

A new genus of the family Enterobacteriaceae is proposed on the basis of its unique biochemical and serological properties. The genus, Levinea (named in honor of Max Levine), is composed of two different species, for which the names Levinea amalonatica and Levinea malonatica are proposed. L. amalonatica is designated as the type species. The type strain of L. amalonatica is 9823 (=ATCC 25405) and the type strain of L. malonatica is 1791 (=ATCC 25408). Information is given which distinguishes the proposed new genus from certain species of Enterobacter and Citrobacter, the genera which it most closely resembles. The similarity of L. amalonatica to organisms in the proposed new genus Padlewskia Macierewicz (9) is discussed.

In Vitro Antibiotic Susceptibility of Pseudomonads Other than Pseudomonas aeruginosa Recovered from Cancer Patients

The increase in occurrence of infections due to opportunistic gram-negative bacilli in patients with impaired host defenses emphasizes the need for information on the antibiotic susceptibility of the organisms that colonize such patients. During a 20-month period, more than 100 pseudomonads which were not Pseudomonas aeruginosa were recovered from cancer patients at the Baltimore Cancer Research Center. These included P. fluorescens, P. putida, P. multivorans (cepacia), P. maltophilia, P. stutzeri, P. alcaligenes, and P. pseudoalcaligenes. Susceptibility tests with 12 antibiotics indicated that the intraspecies antibiograms for many of these species were more uniform than those of P. aeruginosa. The stability of susceptibility patterns allowed the antibiograms to be used as aids in the preliminary differentiation of these organisms. Variable antibiogram patterns were noted among certain species, i.e., P. fluorescens, P. stutzeri, and P. multivorans, whereas each of the other species had essentially one pattern. These in vitro studies showed that some of the Pseudomonas species other than P. aeruginosa were resistant to a number of antibiotics. Among these were antibiotics that are in general use for P. aeruginosa infections. Such differences in antibiotic susceptibilities emphasize the necessity for careful speciation of this group of microorganisms to assure proper epidemiological documentation of colonization and infection, as well as to ensure therapy with an antimicrobial agent to which the organism is susceptible in vitro.

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.

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.

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.