PubMed Health⌕ Search

Biomedical subjects

M Pfaller

Publications and source records attributed to M Pfaller.

50 records · Page 3Linked to original sources

Antimicrobial activity of U-76,252 (CS-807), a new orally administered cephalosporin ester, including recommendations for MIC quality control.

U-76,253A (R-3746), the active metabolite of the new cephalosporin ester, U-76,252 (CS-807), was tested against 4,742 fresh clinical isolates from four large medical centers. U-76,253A was very active against nearly all species of Enterobacteriaceae (87.7% inhibited at less than or equal to 4.0 micrograms/ml). Staphylococcus spp., and the streptococci. The U-76,253A spectrum was superior to the comparison orally administered cephalosporins (cephalexin, cephradine, cefaclor). Pseudomonas spp., Acinetobacter spp., and the enterococci were resistant to U-76,253A and the other tested drugs. Broth microdilution MIC quality control (QC) limits were established for U-76,253A in a multilaboratory investigation using a minimum of 125 MIC determinations per organism. The following MIC QC ranges were recommended; Escherichia coli (ATCC 25922) = 0.25-1.0 micrograms/ml, Staphylococcus aureus (ATCC 29213) = 2.0-4.0 micrograms/ml and Pseudomonas aeruginosa (ATCC 27853) = greater than 32 micrograms/ml.

Administration, Oral↗

Multiple Candida strains in the course of a single systemic infection.

Species and strain variabilities have been monitored during the history of a prolonged Candida infection in a single compromised bone marrow transplant patient by analyzing sugar assimilation patterns, high-frequency switching repertoires, and Southern blot hybridization patterns with two cloned mid-repeat sequences (Ca3 and Ca7) which are species specific for Candida albicans and one cloned mid-repeat sequence (Ct13-8) which is species specific for Candida tropicalis. Evidence is presented that during the course of this infection (i) two strains of C. albicans and three strains of C. tropicalis were distinguished by their switching repertoires, Southern blot hybridization patterns, and sugar assimilation patterns; (ii) the three C. tropicalis strains were in a high-frequency mode of switching; (iii) two C. tropicalis strains coexisted in the blood and three C. tropicalis strains coexisted in the throat at different times during the history of the infection; (iv) amphotericin B treatment selectively removed one of two C. tropicalis strains coexisting in the blood and this strain exhibited greater susceptibility to amphotericin B in vitro (the remaining strain was subsequently removed from the blood by flucytosine treatment); and (v) both the strain removed from the blood by amphotericin B and the strain removed from the blood by flucytosine reappeared several days later at another site of infection. It is demonstrated for the first time that C. tropicalis is capable of high-frequency switching of colony morphology just as C. albicans is, that there is more than one strain-specific switching repertoire in C. tropicalis, and that a C. tropicalis mid-repeat sequence can be used for discriminating species and assessing strain relatedness, as previously demonstrated for C. albicans mid-repeat sequences.

Adult↗

Predictive value of surveillance cultures for systemic infection due to Candida species.

Weekly fungal surveillance cultures (1,542 cultures) of urine (475), stool (520) and oropharyngeal (547) specimens from 111 patients on the bone marrow transplant and hematologic malignancy services were analyzed. Forty-three percent of the patients were colonized by Candida albicans and 10.8% by Candida tropicalis. There were 22 proven systemic fungal infections, ten due to Candida albicans, eight to Candida tropicalis, one each to Candida pseudotropicalis and Torulopsis glabrata, and two to Aspergillus species. Positive surveillance cultures for Candida tropicalis were highly predictive of systemic infection. The finding of two or more positive cultures yielded high positive predictive values (100%) as a function of body site. Positive surveillance cultures for Candida albicans were not predictive of disease but negative cultures for Candida albicans and Candida tropicalis had a high negative predictive value (95-99%). Surveillance culture data for specific Candida species may aid in diagnostic and therapeutic decision making.

Bone Marrow Transplantation↗

The usefulness of screening tests for pyuria in combination with culture in the diagnosis of urinary tract infection.

A prospective study was conducted to examine the usefulness of screening tests for pyuria in combination with culture in the diagnosis of urinary tract infection (UTI) in outpatients. Midstream urine specimens were collected from 340 patients seen in the emergency treatment center (ETC) and were examined for pyuria using the chamber count method and the Leukocyte Esterase Dipstick test (LE; Bio Dynamics, Indianapolis, IN). All specimens were cultured quantitatively using both 0.01 ml and 0.001 ml calibrated bacteriologic loops. A total of 100 UTIs, defined by combined clinical and laboratory critera, were identified. Sixty-four (64%) infections were identified by culture using the standard interpretive breakpoint of greater than or equal to 10(5) CFU/ml and an additional 36 (36%) were detected using the low-count interpretive breakpoint of greater than or equal to 10(3) CFU/ml. We found pyuria detection by either the chamber count method or the LE test to be extremely useful in directing subsequent culture efforts. By using either of the tests for pyuria to determine the significance of low-count bacteriuria (10(3) - less than 10(5) CFU/ml) we were able to achieve maximum sensitivity (92%-99%) and specificity (99.2-99.6%) for the diagnosis of UTI while minimizing the number of specimens in which low numbers of organisms must be evaluated.

Adolescent↗

Variation in methicillin-resistant Staphylococcus aureus occurrence by geographic location and hospital characteristics.

A survey of 162 Veterans Administration Medical Center (VAMC) laboratories performing antimicrobial susceptibility testing was performed to determine variation in reported rates of methicillin-resistant Staphylococcus aureus (MRSA) isolation by geographic location and hospital characteristics. Of the 162 VAMC laboratories surveyed, 136 (84%) provided usable data. The percentage of S aureus isolates reported as resistant to methicillin ranged from 0% to 52% with a mean value of 10% among the 136 survey respondents. MRSA were isolated in every VA Medical District and 96% of all respondent laboratories reported isolating at least one MRSA isolate during the preceding year. These data are considered an underestimate of the time MRSA rate in the VA system due to the fact that many laboratories failed to follow key methodologic guidelines for optimal detection of MRSA. A positive correlation was found between MRSA isolation rate and several measures of hospital size and activity including total beds, total admissions, and total antimicrobial susceptibility tests performed. Geographic clustering of MRSA isolation was observed with distinct areas of very high and very low percentages of S aureus isolates reported as MRSA. The data suggest that the geographic distribution of MRSA within the VA system should be monitored closely for evidence of spread from areas with high-MRSA rates to areas of mid- or low-MRSA rates. Evidence of increased MRSA isolation within these areas may necessitate increased caution in patient referral and transfer patterns within the VA system.

Cross Infection↗

"White-opaque transition": a second high-frequency switching system in Candida albicans.

A second high-frequency switching system was identified in selected pathogenic strains in the dimorphic yeast Candida albicans. In the characterized strain WO-1, cells switched heritably, reversibly, and at a high frequency (approximately 10(-2] between two phenotypes readily distinguishable by the size, shape, and color of colonies formed on agar at 25 degrees C. In this system, referred to as the "white-opaque transition," cells formed either "white" hemispherical colonies, which were similar to the ones formed by standard laboratory strains of C. albicans, or "opaque" colonies, which were larger, flatter, and grey. At least three other heritable colony phenotypes were generated by WO-1 and included one irregular-wrinkle and two fuzzy colony phenotypes. The basis of the white-opaque transition appears to be a fundamental difference in cellular morphology. White cells were similar in shape, size, and budding pattern to cells of common laboratory strains. In dramatic contrast, opaque cells were bean shaped and exhibited three times the volume and twice the mass of white cells, even though these alternative phenotypes contained the same amount of DNA and a single nucleus in the log phase. In addition to differences in morphology, white and opaque cells differed in their generation time, in their sensitivity to low and high temperatures, and in their capacity to form hypae. The possible molecular mechanisms involved in high-frequency switching in the white-opaque transition are considered.

Candida albicans↗

Multicenter comparison of MicroScan and BACTEC blood culture systems.

Recently, MicroScan (Baxter MicroScan Div., W. Sacramento, Calif.) introduced a radiolabeled-blood-culture system that is compatible with the BACTEC 460 (Johnston Laboratories, Inc., Towson, Md.). A multicenter blood culture study was initiated to evaluate this new system. Approximately 20 ml of blood was obtained from each patient and divided equally between BACTEC and MicroScan bottles which were incubated and processed identically. Aerobic bottles were examined twice on days 1 and 2 and once on days 3, 4, 5, 6, and 7. Anaerobic bottles were examined once a day for 7 days. There were 3,451 cultures evaluated, and 414 of these subsequently grew microorganisms. Of these positive cultures, 64 were judged to be contaminated. Of the remaining 350 positive cultures, 253 grew in both systems, 54 grew in BACTEC bottles only, and 43 grew in MicroScan bottles only. The average times to detect positive cultures were 1.8 and 2.1 days by the BACTEC and the MicroScan systems, respectively. No significant difference in the number or kind of organisms recovered or in the detection times for positive cultures was observed between the two blood-culturing systems.

Aerobiosis↗

In vitro inhibitory and bactericidal activity of cefpiramide and seven antipseudomonal agents against Pseudomonas aeruginosa.

Cefpiramide was tested against 493 clinical isolates of Pseudomonas aeruginosa and the results of minimal inhibitory concentration, minimal bactericidal concentration, bactericidal rate, and time-kill synergy studies were compared with those obtained with seven other antipseudomonal agents. The minimal inhibitory concentrations of cefpiramide for P. aeruginosa were comparable to all of the agents tested. Minimal bactericidal concentration results were generally within one twofold dilution of the minimal inhibitory concentration values for all agents tested. Bactericidal rate studies showed that at concentrations of four times the minimal inhibitory concentration, all of the agents produced rapid killing. Results of time-kill synergy studies showed a marked synergistic interaction between cefpiramide and each of three aminoglycosides, gentamicin, tobramycin, and amikacin. These results suggest that cefpiramide may be useful in the therapy of infections due to P. aeruginosa.

Amikacin↗

Late results after correction of tetralogy of Fallot necessitating outflow tract reconstruction. Comparison with results after correction without outflow tract patch.

From 1958 to 1980, at the Department of Cardiovascular Surgery in Munich, 642 patients with Tetralogy of Fallot were corrected and survived the 30th postoperative day. In 140 ( = 21.8%) a valveless outflow tract patch was used. This technique was not needed in 502 ( = 78.2%) patients. Our cases differ from corrections performed today in that the patients were already 10 years old on an average when they underwent primary or secondary corrective surgery. Besides that, they could not benefit from modern methods of myocardial protection at that time. Twenty-five patients ( = 17.9%) with an outflow tract patch died within 25 years postoperatively. The main cause of death (in 68% of all non-survivors) was cardiac in origin. We compared the long-term survival rates of our 140 patch recipients with the rates of our non-patch group (patients without a right ventricular outflow tract patch) using the actuarial method. The difference between the 2 groups, 25 years postoperatively, proved highly significant: 80% survival in the patch group and 93.4% survival in the non-patch group. We conclude that patients with a valveless right ventricular outflow patch should be observed very carefully in a follow-up program. Increasing cardiomegaly postoperatively should be clarified.

Adolescent↗

Effects of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, and L-phenylalanine mustard on B16, Cloudman S91, and Harding-Passey mouse melanomas.

The effects of 5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC), 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU), and L-phenylalanine mustard (L-PAM) have been compared by using three i.p. transplanted mouse melanomas: the B16 melanoma in C57BL/6 mice; the Harding-Passey (HP) malanoma in BALB/c X DBA/2F1 (hereafter called CD2F1) mice; and the Cloudman S91 melanoma in DBA/2 mice. HP melanoma responds well to all three drugs. S91 responds only to L-PAM and MeCCNU. DTIC may accelerate death in mice bearing this tumor. B16 responds well to L-PAM and moderately well to MeCCNU and to multiple injections of DTIC. The best response to DTIC and MeCCNU is given by HP, while the best response to L-PAM is given by S91. Tumor cell-doubling times were found to be 1.5 days for B16, 2 DAYS FOR HP, and 3 days for S91. HP would seem to be the most responsive malanmoma with respect to the 3 agents studied. This may be due to an interaction between the chemotherapeutic agents and the host immune response, since the HP tumor arose in a noninbred mouse and is thus nonsyngeneic with the CD2F1 host. All three tumors appear to be interesting biological models for studying drug combinations and combined therapeutic modalities against melanoma.

Animals↗

The application of molecular and immunologic techniques to study the epidemiology of Legionella pneumophila serogroup 1.

We applied monoclonal antibody typing and restriction endonuclease analysis of plasmid DNA to study 28 clinical and 35 environmental (potable water) isolates of Legionella pneumophila serogroup 1 from three hospitals in Iowa between 1981 and 1986. Monoclonal antibody typing employed a panel of seven antibodies and delineated eight different subtypes. Plasmids were present in 57% of the isolates including 12 of 28 (43%) clinical and 25 of 35 (69%) potable water isolates. The plasmids ranged in size from 28 to 98 kilobase pairs and comprised eight distinct subtypes by restriction endonuclease analysis with Eco RI. Combination of monoclonal antibody and restriction endonuclease subtyping (composite subtyping) revealed 19 different composite subtypes of Legionella pneumophila serogroup 1. The most common composite subtype, 09:04, comprised 29% (18 of 63) of the isolates and was only found in clinical and potable water samples from a single pavilion in hospital A during an outbreak of Legionella pneumophila serogroup 1 pneumonia. Aside from this cluster the diversity of composite subtypes of Legionella pneumophila serogroup 1 observed in clinical and potable water sources over the 5-year period was striking. The combination of monoclonal antibody and restriction endonuclease typing resulted in improved strain delineation and a more useful use of epidemiologic markers for Legionella pneumophila serogroup 1.

Antibodies, Monoclonal↗

In vitro comparison of cefpirome and four other beta-lactam antibiotics alone and in combination with tobramycin against clinical isolates of Pseudomonas aeruginosa.

In vitro susceptibility studies of cefpirome versus cefotaxime, ceftazidime, imipenem, and piperacillin alone and in combination with tobramycin were performed against 153 clinical isolates of Pseudomonas aeruginosa from four medical centers. The minimal inhibitory concentration (MIC) for each antibiotic alone was determined by a standardized dilution method. Antibiotic combination studies were performed using a modified checkerboard technique. Cefpirome alone was more active (MIC90 64 micrograms/ml) than piperacillin (MIC90 128 micrograms/ml) or cefotaxime (MIC90 256 micrograms/ml) but less active than imipenem (MIC90 2 micrograms/ml) or ceftazidime (MIC90 32 micrograms/ml). The addition of tobramycin reduced the MICs of all of the beta-lactam antibiotics except for imipenem. The MIC90 for cefpirome when combined with tobramycin was 8 micrograms/ml compared to 16 micrograms/ml for cefotaxime and piperacillin, 8 micrograms/ml for ceftazidime, and 4 micrograms/ml for imipenem. The combination of tobramycin and cefpirome proved to be additive or synergistic for 82% of the isolates (highest rate) compared to 31% with imipenem (lowest rate). The potent in vitro antipseudomonal activity of cefpirome alone and in combination with an aminoglycoside (tobramycin) suggests that this agent may play a useful role in the therapy of infections due to P. aeruginosa.

Anti-Bacterial Agents↗

Application of DNA probes to antimicrobial susceptibility testing of Legionella pneumophila.

The commercial availability of a DNA probe assay for the detection of Legionella (Gen-Probe Incorporated, San Diego, CA) provides a unique opportunity to investigate the application of this technology to antibiotic susceptibility testing of L. pneumophila. We examined the ability of erythromycin, rifampin, and ciprofloxacin to kill L. pneumophila in buffered ACES-yeast extract broth (YEB). The test organism was incubated for a total of 96 hr in the presence of 10 micrograms/ml erythromycin, 1 micrograms/ml rifampin, or 1 micrograms/ml ciprofloxacin. Growth was monitored at 24-hr intervals by quantitative plating and the DNA probe assay. The correlation between organism concentration [colony-forming units (CFU) per ml] and DNA probe activity (counts per min) was excellent (r = 0.97). The percent decrease in CFU/ml at 96 hr relative to control counts was greater than 99% for erythromycin, rifampin, and ciprofloxacin. The percent decrease in CPM at 96 hr versus control was 87% for erythromycin, 89% for rifampin, and 93% for ciprofloxacin. This data documents a novel application of DNA probe technology, which may be useful in future studies of in vitro susceptibility of Legionella to various agents.

Anti-Bacterial Agents↗