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Biomedical subjects

M A Pfaller

Publications and source records attributed to M A Pfaller.

At least 469 records · Page 26Linked to original sources
PubMed1983

Oxygen enhances the antimalarial activity of the imidazoles.

We have previously reported the antimalarial activity of imidazoles and amphotericin B against chloroquine-resistant Plasmodium falciparum. We now report the enhancement of imidazole activity in an atmosphere with 17-18% oxygen (the candle jar) vs. 3% or 0.3% oxygen. Based on both morphologic and radiometric testing, smaller amounts of the imidazoles were required to inhibit parasite growth by 50% in the candle jar vs. 3% or 0.3% oxygen. The use of older (more oxidant-sensitive) red cells also enhanced the antimalarial activity of ketoconazole. Neither increased concentrations of oxygen nor the use of older red cells affected the activity of amphotericin B. These results suggest that the imidazoles may exert their antimalarial effect by increasing the oxidant stress on the red cell-parasite complex.

Amphotericin B↗
PubMed1982

Lysis of Plasmodium falciparum by ferriprotoporphyrin IX and a chloroquine-ferriprotoporphyrin IX complex.

Ferriprotoporphyrin IX (FP) and a chloroquine-FP complex lysed isolated Plasmodium falciparum parasites as judged by decreases in the turbidity of parasite suspensions and by ultrastructural changes. Exposure of parasite suspensions to 50 microM FP or to a complex formed from 50 microM FP and 20 MicroM chloroquine reduced the number of identifiable parasites and caused swelling and loss of internal detail in those that were identifiable. The amount of lysis was dose-dependent over the range of 10 to 50 microM FP. Formation of a chloroquine-FP complex reduced, but did not eliminate, the toxicity of FP. Since there is evidence indicating that a chloroquine-FP complex forms when chloroquine-susceptible parasites are exposed to chloroquine, we suggest that accumulation of this complex may account for the chemotherapeutic effect of chloroquine against P. falciparum.

Chloroquine↗
PubMed1982

Clinical laboratory comparison of a slide blood culture system with a conventional broth system.

The recovery of bacteria and fungi from blood cultures was compared in conventional tryptic soy broth (TSB) bottles and in TSB bottles with an agarcoated slide attachment. A total of 2,662 sets of blood cultures, including 413 that were positive (15.5%), were evaluated. Significantly more gram-positive and gram-negative bacteria were recovered in the slide culture bottles than in conventional bottles (299 versus 253 isolates). Growth of gram-positive organisms and fungi was detected in the slide culture bottles 24 to 48 h earlier than in the TSB bottles. In addition, 76% of the isolates in the slide culture system were detected on the agar slide. In comparison, only 40% of the isolates in the TSB bottles were detected initially by blind subculturing. The incidences of contamination were 2.7% (71 cultures) for the slide culture system and 1.5% (39 cultures) for the TSB bottles.

Bacteria↗
PubMed1982

Heparin interferes with the radioenzymatic and homogeneous enzyme immunoassays for aminoglycosides.

Heparin interferes with measurement of aminoglycosides in serum by biological, radioenzymatic, and homogeneous enzyme immunoassay techniques, but not with radioimmunoassay. At concentrations greater than or equal to 10(5) and greater than or equal to 3 X 10(6) USP units/L, respectively, it interferes with the radioenzymatic assay by inhibiting the gentamicin 3-acetyltransferase (EC 2.3.1.60) and kanamycin 6'-acetyltransferase (EC 2.3.1.55) enzymes used in the assay. It interferes with the homogeneous enzyme immunoassays for gentamicin and tobramycin (at concentrations greater than or equal to 10(5) and greater than or equal to 10(4) USP units/L, respectively), but not with the commercially available homogeneous enzyme immunoassays for other drugs. Heparin interference with the homogeneous enzyme immunoassay for aminoglycosides requires both the heparin polyanion and glucose-6-phosphate dehydrogenase (EC 1.1.1.49) bound to a cationic aminoglycoside. This interference can be reproduced with dextran sulfate (but not dextran), and does not occur with free enzyme (glucose-6-phosphate dehydrogenase) alone. We describe how heparin interferes with these two assays and demonstrate interference at heparin concentrations that may be present in intravenous infusions or in seriously underfilled blood-collection tubes.

Amikacin↗
PubMed1974

Antileishmanial effect of allopurinol.

Allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine) has been shown to inhibit the growth of Leishmania braziliensis in vitro at concentrations which are attainable in human tissues and body fluids. This compound is believed to act by interdicting the de novo synthesis of pyrimidines, probably through the formation of allopurinol ribotide. Its lack of toxicity makes it a potential candidate for animal experimentation and it may serve as a prototype for other agents with similar mechanisms of action.

Allopurinol↗
PubMedDate not supplied

Susceptibility of nosocomial isolates of Candida species to LY121019 and other antifungal agents.

LY121019 is a novel analog of the polypeptide antifungal antibiotic echinocandin B. We investigated the in vitro activity of LY121019, amphotericin B, ketoconazole and 5-fluorocytosine against 131 nosocomial isolates of Candida species: C. albicans (n = 50), C. tropicalis (n = 30), C. rugosa (n = 12), C. parapsilosis (n = 11), C. lusitaniae (n = 10), C. guillermondii (n = 9), and C. krusei (n = 9). In vitro susceptibility testing was performed using a broth microdilution method. The minimal inhibitory concentrations (MIC) of LY121019 were less than or equal to that of the other antifungal agents against C. albicans and C. tropicalis but were generally higher for the other species of Candida. Paradoxical growth at high concentrations, but not at low concentrations, of LY121019 was observed with isolates of C. albicans and C. tropicalis.

Amphotericin B↗
PubMedDate not supplied

Susceptibility of clinical isolates of Candida spp. to terconazole and other azole antifungal agents.

Terconazole is a triazole ketal derivative with potent, broad-spectrum antifungal activity. We investigated the in vitro activity of terconazole, miconazole, and clotrimazole, against 94 clinical isolates of Candida spp.: C. albicans (n = 68), C. tropicalis (n = 18), and C. parapsilosis (n = 8). In vitro susceptibility testing was performed using a broth microdilution method. The minimal inhibitory concentrations of terconazole were less than those of miconazole against C. albicans and C. parapsilosis but higher against C. tropicalis. Terconazole was more active than clotrimazole against C. parapsilosis and less active against C. albicans and C. tropicalis. Terconazole inhibited the uptake of 14C-labeled glucose, leucine, and hypoxanthine into C. albicans and caused the rapid release of intracellular K+. Based on these studies, terconazole has promising anticandidal activity and warrants further in vitro and in vivo investigation.

Antifungal Agents↗
PubMedDate not supplied

Effects of terconazole and other azole antifungal agents on the sterol and carbohydrate composition of Candida albicans.

The effects of terconazole, a triazole antifungal, on the sterol and carbohydrate composition of Candida albicans was compared with that of three imidazoles: clotrimazole, miconazole, and butoconazole. Exposure of C. albicans to terconazole resulted in a profound depletion of ergosterol with a corresponding increase in lanosterol content versus control cells. Carbohydrate analysis revealed a significant (245%) increase in chitin and a minimal effect on glucan and mannan in terconazole-treated cells. Similar effects on sterol and carbohydrate composition were observed with clotrimazole and miconazole. Butoconazole had a similar effect on sterol composition but had no effect on carbohydrate composition. The decreased ergosterol and increased lanosterol content is consistent with 14 alpha-demethylase inhibition by terconazole and the other azoles. The increase in cell wall chitin is most likely due to deregulation of chitin synthesis secondary to ergosterol depletion in the cell membrane. Because both chitin and ergosterol are critical components of the fungal cell, perturbation of the production and localization of these components by terconazole is likely to contribute to the selective toxicity of this compound for C. albicans and other fungi.

Antifungal Agents↗
PubMedDate not supplied

Biotyping of coagulase-negative staphylococci. 108 isolates from nosocomial bloodstream infections.

Using simple, readily available typing methods, we evaluated 108 strains of coagulase-negative staphylococci that were causally related to bloodstream infections: 95% (103 of 108) of the isolates were identified as Staphylococcus epidermidis and were divided into 18 biotypes by API Staph-Trac. A single biotype (biotype A, 6606113) accounted for greater than 50% of the isolates of S. epidermidis. Biotype A was further divided into seven subtypes by slime production and synergistic hemolysis; however, 66% of the isolates in biotype A remained in two major subtypes, 1a (strongly slime-positive and synergistic hemolysis-positive) and 2a (strongly slime-positive and synergistic hemolysis-negative). The addition of the antibiotype further separated the isolates into individual strains or into small groups of organisms. A significant correlation was noted between synergistic hemolysis and the three most resistant antibiotypes (p = 4.2 X 10(-5); OR = 5.8; CI95, 2.2-15.2). Each biotype, subtype, and antibiotype was further divided into multiple unique strains by plasmid pattern analysis. In most clinical situations the combination of API Staph-Trac, antibiotic profile, slime production, and synergistic hemolysis provides adequate strain discrimination. Plasmid pattern analysis adds important information in specific clinical situations and may be invaluable for epidemiologic investigations.

Bacterial Typing Techniques↗
PubMedDate not supplied

The use of biotyping and DNA fingerprinting in typing Candida albicans from hospitalized patients.

The application of typing procedures for the purpose of strain differentiation among isolates of Candida albicans obtained from hospitalized patients has been limited. We have applied biotyping and DNA restriction fragment analysis (DNA fingerprinting) by using EcoRI to the study of C. albicans isolates obtained from hospitalized patients. A total of 68 isolates from 15 patients were studied. Thirteen subtypes were identified by biotyping, 8 by DNA fingerprinting, and 21 by a combination of the biotyping and DNA fingerprinting approaches (composite subtype). Both techniques were highly reproducible. In examining the strain variation among isolates obtained from multiple anatomic sites over time, we found that similar, if not identical, strains were recovered from the oropharynx, urine, stool, and blood in a given patient, and these strains persisted. Only rarely did two patients share the same composite subtype suggesting sporadic nosocomial transmission. The combination of biotyping and DNA fingerprinting improved strain discrimination compared to either method alone. Further investigation with these and other epidemiologic typing methods will be necessary to enhance the understanding of the epidemiology and pathogenesis of candidiasis in hospitalized patients.

Bacterial Typing Techniques↗
PubMedDate not supplied

Antimicrobial activity of cefpirome. An update compared to five third-generation cephalosporins against nearly 6000 recent clinical isolates from five medical centers.

Cefpirome, cefotaxime, ceftazidime, cefoperazone, ceftizoxime, and ceftriaxone were tested against approximately 6000 fresh clinical isolates from five medical centers. For 3031 strains of Enterobacteriaceae tested, cefpirome consistently had the lowest MIC50s and lowest percentage of resistant strains. Cefpirome was also the most active agent against the 2138 Gram-positive cocci tested; Staphylococcus haemolyticus was uniformly resistant to all agents tested. Against 791 nonenteric Gram-negative bacilli, the activity of cefpirome was most comparable to that of cefoperazone and slightly less active than ceftazidime. Among the current third-generation cephalosporins, cefotaxime and cefoperazone emerged as having better overall balanced activity. Ceftazidime displayed poorest coverage against Enterobacteriaceae and Gram-positive organisms. Ceftizoxime also provided compromised coverage of staphylococci and nonenteric Gram-negative bacilli. Cefpirome remains as active as originally described in 1984 and possesses a slightly wider spectrum of activity against contemporary aerobic pathogens compared to currently marketed third-generation cephalosporins.

Bacteria↗
PubMedDate not supplied

The clinical microbiology laboratory as an aid in infection control. The application of molecular techniques in epidemiologic studies of methicillin-resistant Staphylococcus aureus.

A microbiologic surveillance study was performed in order to estimate the point prevalence, source, and nosocomial acquisition of methicillin-resistant Staphylococcus aureus (MRSA) within the Iowa City Veterans Affairs Medical Center (IC VAMC). Immediately following the microbiologic surveillance study, a cluster of nosocomial MRSA infections was detected by routine infection control surveillance. An epidemiologic investigation was conducted and all isolates of MRSA detected during the microbiologic surveillance study and the subsequent cluster of nosocomial infections were characterized by restriction endonuclease analysis of plasmid DNA (REAP). REAP subtyping defined a total of ten distinct subtypes from 24 patients infected or colonized with MRSA. The documentation of a single subtype of MRSA (subtype A2) in nine patients from the surgical service, eight of which were hospitalized in the surgical intensive care unit, provided convincing evidence of a breakdown of infection control practices in that unit. REAP subtyping was a highly discriminating means of identifying different subtypes among the various isolates of MRSA and was useful in directing infection control efforts to specific problem areas within the hospital. Molecular typing methods, such as REAP, when used appropriately in conjunction with careful epidemiologic investigation provide an effective approach to the investigation and control of the spread of MRSA within the hospital.

Clindamycin↗
PubMedDate not supplied

Development of Neisseria gonorrhoeae in vitro susceptibility test methods for cefixime including quality control guidelines.

Cefixime was tested in a multilaboratory study to establish susceptibility testing interpretive criteria and quality control (QC) guidelines for Neisseria gonorrhoeae. Interpretive criteria were established by using triplicate testing of 102 representative gonococcal strains. Only a susceptible category was proposed for cefixime (greater than or equal to 31 mm and less than or equal to 0.25 micrograms/ml) because of very rare, resistant isolates. QC ranges [N. gonorrhoeae American Type Culture Collection (ATCC) 49226] were established using multiple GC agar lots, three disk lots, and a number of test replicates consistent with the National Committee for Clinical Laboratory Standards (NCCLS) M23-T guidelines. Cefixime was stable in GC agar medium for at least 21 days when stored at 2 degrees-5 degrees C. Oral third-generation cephalosporins, such as cefixime, appear to represent potentially useful clinical alternatives to parenteral drugs of the same class for single-dose therapy of gonorrhea.

Cefixime↗
PubMedDate not supplied

Application of restriction endonuclease analysis of chromosomal DNA in the study of Staphylococcus aureus colonization in continuous ambulatory peritoneal dialysis patients.

The relationship between nasal and skin colonization with Staphylococcus aureus and subsequent infection in continuous ambulatory peritoneal dialysis (CAPD) patients in Brazil has been documented by restriction endonuclease analysis of plasmid DNA. However, S. aureus strains without detectable plasmids have been identified. Using restriction endonuclease analysis of chromosomal DNA hybridized with an rRNA gene probe, we document the diversity of S. aureus strains without detectable plasmids colonizing CAPD patients. Ten paired strains without detectable plasmids from five patients were studied by restriction endonuclease analysis of chromosomal DNA and by phage typing. Five different profiles were obtained by restriction endonuclease analysis of chromosomal DNA. Although four of the ten paired isolates were nontypeable by phage typing, all were discriminated by restriction endonuclease analysis of chromosomal DNA. These results demonstrate that restriction endonuclease analysis of chromosomal DNA is a useful epidemiologic tool and complements the restriction endonuclease analysis of plasmid DNA of S. aureus by providing a means of typing strains without detectable plasmids.

Bacteriophage Typing↗
PubMedDate not supplied

In vitro activity of ampicillin, amoxicillin, ampicillin-sulbactam, and amoxicillin-clavulanic acid against consecutive clinical isolates of Enterobacteriaceae.

Ampicillin was generally twice as active as amoxicillin against 2440 consecutive isolates of Enterobacteriaceae from five medical centers. When beta-lactamase inhibitors were added to the penicillins, there was a significant increase in susceptibility. The magnitude of the increased susceptibility to ampicillin-sulbactam (A-S) and amoxicillin-clavulanic (A-C) acid varied with the species and types of beta-lactamases elaborated. Although cross-susceptibility and cross-resistance between ampicillin and amoxicillin was nearly complete, major differences were documented between A-S and A-C with 6.7% of our consecutive isolates of Enterobacteriaceae. The clinical significance of these findings remains uncertain, but they may help explain some of the discrepancies occasionally observed by clinical microbiologists with the combination drugs.

Amoxicillin↗