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Biomedical subjects

M A Pfaller

Publications and source records attributed to M A Pfaller.

At least 415 records · Page 23Linked to original sources
PubMed1990

Polyamine depletion and growth inhibition of Cryptococcus neoformans by alpha-difluoromethylornithine and cyclohexylamine.

The ability of two known inhibitors of polyamine synthesis alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), and cyclohexylamine, an inhibitor of spermidine synthase, to inhibit the in vitro growth and polyamine synthesis of clinical isolates of Cryptococcus neoformans was examined. Treatment of C. neoformans with either DFMO or cyclohexylamine resulted in depletion of cellular polyamines and inhibition of growth. Cryptococcus neoformans was shown to lack detectable spermine and to require high concentrations of spermidine, but not putrescine, for growth. The growth inhibition by DFMO and cyclohexylamine was reversed by exogenous polyamines. These findings document the ability of cyclohexylamine and DFMO to inhibit polyamine synthesis and growth in clinically important isolates of C. neoformans.

Cryptococcus neoformans↗
PubMed1990

Comparative in vitro activity of the new quinolone sparfloxacin (CI-978, AT-4140) against nosocomial gram-negative bloodstream isolates.

The in vitro activity of sparfloxacin (CI-978, AT-4140), a new quinolone which is active against gram-negative and gram-positive bacteria, and nine other broad-spectrum antibiotics was tested against 128 gram-negative nosocomial bloodstream isolates from separate patients. Sparfloxacin and ciprofloxacin were among the most potent antibiotics against Escherichia coli (n = 40), Enterobacter cloacae (n = 18), Klebsiella oxytoca (n = 13), and Klebsiella pneumoniae (n = 19), with MIC90 values of less than or equal to 0.25 microgram/ml. Ciprofloxacin was slightly more potent than sparfloxacin against Serratia marcescens (n = 14), the MIC90 values being 0.25 and 1.0 micrograms/ml respectively, although all strains were susceptible to both agents. Sparfloxacin was slightly less potent than ciprofloxacin against Pseudomonas aeruginosa (n = 24), the MIC90 values being 4.0 and 0.5 micrograms/ml respectively. Overall, the in vitro activity of sparfloxacin compared favorably with that of ciprofloxacin and the other broad spectrum agents tested against nosocomial gram-negative bloodstream isolates.

Amikacin↗
PubMed1990

In vitro comparison of mezlocillin and piperacillin plus tobramycin or gentamicin versus 100 gram-negative nosocomial bloodstream isolates.

We compared the in vitro activity of mezlocillin and piperacillin, alone and in combination with tobramycin or gentamicin, against clinical isolates of gram-negative bacilli from hospitalized patients with 100 distinct episodes of nosocomial bacteremia. The minimum inhibitory concentrations (MICs) necessary to inhibit 50% and 90% of isolates showed that piperacillin was most active against Pseudomonas aeruginosa. The MIC needed to inhibit 90% of isolates also showed that mezlocillin was more active against Enterobacter cloacae. Activities of the two acylaminopenicillins were comparable against the rest of the isolates. Combining the acylaminopenicillins with either gentamicin or tobramycin decreased the MICs fourfold or more for both combinations. Synergy occurred more frequently with mezlocillin-gentamicin (12%), followed by piperacillin-tobramycin (9%), mezlocillin-tobramycin (6%), and piperacillin-gentamicin (5%). Antagonism for Enterobacteriaceae isolates was observed most frequently with the combination of piperacillin plus tobramycin (20%), followed by mezlocillin plus tobramycin (17.6%), piperacillin plus gentamicin (12.9%), and mezlocillin plus gentamicin (8.2%). There are very few differences in the activities of mezlocillin and piperacillin combined with either gentamicin or tobramycin versus nosocomial gram-negative bloodstream isolates.

Drug Synergism↗
PubMed1990

Effect of serum on the in vitro activities of 11 broad-spectrum antibiotics.

We evaluated the effect of serum on the in vitro activities of 11 antimicrobial agents against gram-negative isolates obtained from 100 patients with nosocomial bacteremia. The test organisms included 25 stains of Pseudomonas aeruginosa and 75 strains of the family Enterobacteriaceae. MICs were determined by broth microdilution with Mueller-Hinton broth alone or supplemented with 25 or 50% pooled, heat-inactivated human serum (25S or 50S, respectively). Among the antibiotics evaluated, the protein binding ranged from 9 to 95%. The antibiotics tested and their MICs for 90% of the strains tested in 50S included ciprofloxacin (0.12 micrograms/ml), ceftazidime (1 micrograms/ml), imipenem (1 micrograms/ml), aztreonam (4 micrograms/ml), cefpirome (4 micrograms/ml), cefotaxime (16 micrograms/ml), cefoperazone (16 micrograms/ml), desacetylcefotaxime plus cefotaxime (32 micrograms/ml), ceftriaxone (greater than 32 micrograms/ml), ticarcillin (128 micrograms/ml), and desacetylcefotaxime (greater than 128 micrograms/ml). MICs for 90% of the strains tested were calculated with 95% confidence intervals to show the precision of the MICs for these strains. With the exceptions of ceftriaxone (greater than 95% protein bound) and cefoperazone (90% protein bound), serum had no significant effect on the in vitro activities of various agents. A fourfold-or-greater increase in the MIC of ceftriaxone was observed in 45 of 100 isolates with 50S and in 30 of 100 isolates with 25S. With cefoperazone, 17 of 100 isolates demonstrated more than 2 twofold dilution increases in 50S. Testing of antibiotics which were less protein bound illustrated minor effects primarily with members of the Enterobacteriaceae. The presence of serum did not adversely affect the in vitro activities of broad-spectrum agents against these nosocomial isolates.

Anti-Bacterial Agents↗
PubMed1990

Collaborative investigation of variables in susceptibility testing of yeasts.

A multicenter study was performed to evaluate the effect of medium, incubation time (24 and 48 h), and temperature (30 and 35 degrees C) on intra- and interlaboratory variations in MICs of flucytosine, amphotericin B, and ketoconazole for yeasts. Testing was performed on coded isolates of Candida species (11 strains) and Cryptococcus neoformans (2 strains) by using a standard macrodilution protocol 11 laboratories. Four chemically defined media buffered to pH 7.0 with morpholinepropanesulfonic acid were evaluated, including buffered yeast nitrogen base, synthetic amino acid medium-fungal, RPMI 1640 medium, and high-resolution antifungal assay medium. Intralaboratory variability was less than or equal to fourfold for 97% of the replicate sets of data. The highest level of interlaboratory agreement, irrespective of antifungal agent or incubation conditions, was observed with RPMI 1640 medium. Intralaboratory variability was less than or equal to fourfold for 93% of the determinations with ketoconazole and 100% with flucytosine tested in RPMI 1640 medium at 35 degrees C for 24 h. Variability in amphotericin B results was less than or equal to fourfold for 81% of the determinations in RPMI 1640 medium at 35 degrees C for 48 h. The rank order of MICs within each antifungal test group was similar among the various laboratories and was generally in agreement with the reference rank order regardless of the test medium that we used.

Amphotericin B↗
PubMed1990

Characterization of the sequence of colonization and nosocomial candidemia using DNA fingerprinting and a DNA probe.

The objective of this hospital-based study was to determine the relationship between colonizing and infecting strains of Candida species and Torulopsis glabrata. Surveillance cultures from high-risk patients were paired with subsequent bloodstream isolates. Organisms were typed by using restriction endonuclease digestion of chromosomal DNA with BstNI and EcoRI, followed by Southern hybridization with a DNA probe (pBD4) derived from Saccharomyces cerevisiae. Sixteen patients for whom documented colonization preceded documented bloodstream infection were identified. The mean time between obtainment of surveillance isolates and obtainment of bloodstream isolates was 8 days, with a range of 1 to 423 days. For 15 (94%) of 16 patients, the DNA fingerprint pattern (using BstNI) of the surveillance isolate was identical to that of the bloodstream isolate. Isolates from 13 (81%) of 16 patients were unique to those patients. Typing by Southern hybridization with the pBD4 probe was less discriminating. We conclude that for a well-defined subset of hospitalized patients who were colonized by Candida species before developing nosocomial candidemia, the colonizing and infecting strains were identical, suggesting endogenous acquisition of infection. Restriction endonuclease digestion of chromosomal DNA was shown to be a discriminating and reproducible typing method for Candida species and T. glabrata.

Blotting, Southern↗
PubMed1990

Vancomycin resistance in Staphylococcus haemolyticus causing colonization and bloodstream infection.

The increase in the incidence of infections due to beta-lactam-resistant coagulase-negative staphylococci has resulted in expanded use of vancomycin for such infections. Despite this, coagulase-negative staphylococci have remained susceptible to vancomycin in recent years. This report describes a strain of Staphylococcus haemolyticus with increased resistance to vancomycin (MIC, 8.0 to 16 micrograms/ml). S. haemolyticus was initially isolated from a patient with acute leukemia and neutropenia in surveillance throat and stool cultures. The microdilution vancomycin MICs for these isolates were 1.0 to 2.0 micrograms/ml. Subsequent S. haemolyticus isolates from the bloodstream and tracheal aspirate occurred in the setting of prolonged empirical vancomycin therapy. MICs for these isolates were 8.0 to 16 micrograms/ml. Further vancomycin resistance (MIC, 32 micrograms/ml) could be selected for in vitro in all four isolates. Restriction endonuclease analysis of plasmid DNA indicated that the isolates were very closely related and likely to be of the same strain. We conclude that colonization with a vancomycin-susceptible strain of S. haemolyticus was subsequently linked to a nosocomial bloodstream infection with an apparently identical strain with intermediate levels of vancomycin resistance. Prolonged empirical vancomycin therapy was temporally associated with this episode.

Aged↗
PubMed1990

Cardiovascular surgery prophylaxis. A randomized, controlled comparison of cefazolin and cefuroxime.

A prospective double-blind trial was performed at a tertiary care center to evaluate perioperative cephalosporin prophylaxis in cardiac operations. Patients were randomized to receive either cefazolin (n = 104) or cefuroxime (n = 109), the preoperative dose being given within 1 hour before the initial incision. Drugs were continued for 48 hours (cefazolin, 1 gm intravenously every 8 hours; cefuroxime, 1.5 gm intravenously every 12 hours). Postoperative infections were assessed by trained nurse clinicians, and data were analyzed by the intention-to-treat principle. Sternal wound infections or mediastinitis occurred in one of 104 patients treated with cefazolin and 10 of 109 treated with cefuroxime (p = 0.01). Deep sternal wounds (including mediastinitis and sternal osteomyelitis) occurred in none of the cefazolin-treated patients and five cefuroxime-treated patients (p = 0.06). Although overall nosocomial infection rates were similar (16.3 versus 19.3 per 100), wound infection occurred somewhat more frequently with streptococci (groups B and D) in patients receiving cefazolin (four versus zero, p = 0.110); conversely staphylococcal infections were more frequent in the cefuroxime group (seven versus one, p = 0.066). Mean and median postoperative stay was 1 day shorter in the cefazolin group. In contrast to findings of a previous report, our data indicate that cefazolin prevented more sternal wound infections than cefuroxime, a finding that supports prophylaxis with a first-generation cephalosporin.

Adult↗
PubMed1989

Plasma tumor necrosis factor levels in patients with presumed sepsis. Results in those treated with antilipid A antibody vs placebo.

Using an enzyme-linked immunosorbent assay, we measured plasma levels of tumor necrosis factor (TNF) in 38 patients who were treated with either antilipid A antibody or a placebo for presumed gram-negative bacteremia. Sixteen of the 38 patients had positive blood cultures: 14 with gram-negative rods and 2 with Streptococcus pneumoniae. Initial serum samples for TNF determinations were obtained within 2 to 72 hours (mean, 18.8 hours) after the onset of clinical signs of sepsis. Six (16%) of 38 patients had detectable TNF levels: 4 of 14 with positive blood cultures for gram-negative rods but only 2 of 22 with negative blood cultures (odds ratio, 4; 95% confidence limits, 0.5 and 24.3). Of the 6 patients, 4 had received the placebo and 2 had received the antibody. Tumor necrosis factor levels did not predict adult respiratory distress syndrome, shock, disseminated intravascular coagulation, renal failure, or mortality. The highest TNF levels (500 and 250 pg/mL) were observed in 2 patients with Enterobacter cloacae bacteremia who had received the placebo and antilipid A antibody, respectively. The other 2 patients with bacteremia and detectable TNF levels had positive blood cultures for Haemophilus influenzae (50 pg/mL) and Bacteroides fragilis (120 pg/mL), respectively. Despite negative blood cultures, the remaining 2 patients repeatedly had detectable TNF levels and a clinical picture consistent with gram-negative sepsis.

Antibodies, Monoclonal↗
PubMed1989

Coagulase-negative staphylococcal bacteremia. Mortality and hospital stay.

OBJECTIVE: To determine the attributable mortality and the excess length of hospital stay resulting from coagulase-negative staphylococcal bacteremia. DESIGN: Matched historical cohort study. SETTING: Large university-based tertiary care center. PATIENTS: Of 171 patients with hospital-acquired coagulase-negative staphylococcal bacteremia identified by prospective surveillance of nosocomial infections from 1 July 1984 to 30 June 1987, 118 met criteria for the study and were matched to a control patient by age, sex, primary diagnoses, operative procedures, and date of admission. MEASUREMENTS AND RESULTS: Success was achieved in 621 of 650 (96%) variables used for matching. Staphylococcus epidermidis accounted for 92% of the bacteremias. Twenty cases (17%) had evidence of septic shock, and 10 had disseminated intravascular coagulation. The mortality rate in cases was 36 of 118 (30.5%) compared with 20 of 118 (16.9%) in controls. The attributable mortality was 13.6% (95% CI, 4.2 to 22.9) and the risk ratio for dying was 1.8 (95% CI, 1.2 to 2.7; P = 0.006). The median length of stay was 46 days for cases and 37.5 for controls (P = 0.0002). CONCLUSIONS: Coagulase-negative staphylococci, the leading organisms causing hospital-acquired bacteremias, are associated with mortality in excess of that due to the underlying diseases alone. Moreover, they significantly prolong the length of hospital stay. These findings show the importance of coagulase-negative staphylococcal bacteremia in hospitalized patients.

Adolescent↗
PubMed1989

Nosocomial gram-negative bloodstream isolates: a comparison of in vitro antibiotic potency.

Nosocomial bloodstream infections add to the morbidity, mortality and length of hospitalization that is attributed to the underlying diseases alone. We have compared the in vitro potency of fifteen antibiotics against 136 isolates from clinically significant nosocomial gram-negative bacteraemias. Ciprofloxacin was the most potent antibiotic and had the broadest spectrum of activity (98% of isolates susceptible, MIC90 range: 0.06-0.5 micrograms ml-1). We subjected all isolates to beta-lactamase induction but antibiotic susceptibility was unaffected by this procedure.

Anti-Bacterial Agents↗
PubMed1989

Use of cellular hydrophobicity, slime production, and species identification markers for the clinical significance of coagulase-negative staphylococcal isolates.

Determining the clinical relevance of coagulase-negative staphylococci isolated from cultures of clinical specimens remains a common dilemma. One hundred eighteen strains of coagulase-negative staphylococci isolated from patients with and without indwelling foreign bodies were characterized with regard to cell-surface hydrophobicity, slime production, and species to determine the predictive value of these phenotypic markers in distinguishing clinically significant from insignificant isolates. The single test with the highest positive predictive value was hydrophobicity (79%). Hydrophobicity and speciation had the greatest combined predictive value of any two tests (89%), and this increased to only 90% when determination of slime production was added. These tests provide additional clinical information when coagulase-negative staphylococci are isolated in culture.

Bacterial Adhesion↗
PubMed1989

Infection control: opportunistic fungal infections--the increasing importance of Candida species.

Candida spp are clearly among the most important of the opportunistic fungal pathogens that cause nosocomial infections. Given the increasing incidence, high attributable mortality and excess length of stay associated with nosocomial candidemia, it is imperative that more effective preventive, diagnostic and therapeutic measures be developed to deal with this emerging group of pathogens. Implicit in these issues is the need for an increased understanding of the epidemiology of nosocomial candidiasis. The development of new epidemiologic typing methods provides useful tools that can assist in clinical and epidemiologic investigation. These studies are essential to the rational development of effective measures to prevent and to control nosocomial infections caused by Candida spp.

Bacterial Typing Techniques↗
PubMed1989

In-vitro susceptibility of nosocomial gram-negative bloodstream pathogens to quinolones and other antibiotics--a statistical approach.

We examined the in-vitro activity of 12 antibiotics against Gram-negative bacillary isolates from 141 distinct episodes of nosocomial bloodstream infection occurring from July 1984 through November 1986. At least ten strains of each of the seven most frequently encountered species were tested. Relative potency was carefully assessed by extending the concentrations from 0.004 to 64 mg/l in microdilution tests performed in duplicate. We estimated MIC50 and MIC90 and, importantly, calculated 95% confidence intervals (CI95) for MIC90. Against all isolates, ciprofloxacin, the most potent antibiotic, had an MIC50 of 0.03 and an MIC90 of 0.13 (CI95 0.11 to 0.16 mg/l). Norfloxacin and enoxacin had MIC90 of 0.50 and 0.71 mg/l, respectively. Imipenem, ceftazidime, aztreonam, and cefoperazone had MIC90 of 1.0, 2.0, 5.3, and 5.7 mg/l, respectively. Both cefotaxime and ceftriaxone had MIC90 of 16 mg/l (CI95 13-19.7 mg/l). For tobramycin, gentamicin and amikacin, the MIC90 values were 1.4, 5.7, and 8 mg/l, respectively. Against Pseudomonas aeruginosa (n = 26), Serratia marcescens (n = 19), and Klebsiella pneumoniae (n = 26), the CI95s about the MIC90 for ciprofloxacin were 0.31-0.81, 0.07-0.23, and 0.04-0.10 mg/l, respectively. For optimal comparison of antibiotics used to treat hospital-acquired bacteraemias, only clinically significant nosocomial bloodstream isolates should be studied with regard to their antibiotic susceptibilities; the isolates should be unique (only one isolate per episode of bacteraemia occurring over a defined period of time); an adequate number of isolates of a particular species should be studied; MICs should be determined over a wide range of concentrations; and both the MIC90 and the CI95 should be reported.

4-Quinolones↗
PubMed1989

Multicenter in vitro evaluation of SM-7338, a new carbapenem.

A new carbapenem, SM-7338, was compared with imipenem, cefotaxime, and ceftazidime at five medical centers. Nearly 6,000 strains were tested by reference methods of the National Committee for Clinical Laboratory Standards, and SM-7338 inhibited the largest percentage of gram-negative bacilli. Its spectrum included all members of the family Enterobacteriaceae (99.7% were susceptible to less than or equal to 4 micrograms/ml), Pseudomonas spp. (but not Xanthomonas maltophilia), and Acinetobacter spp. The potency and spectrum of SM-7338 against the gram-positive organisms were less than those of imipenem and superior to those of ceftazidime. Only the enterococci and some oxacillin-resistant staphylococci were less susceptible to SM-7338 (MICs for 90% of isolates, greater than or equal to 8 micrograms/ml). Organisms resistant to ceftazidime were generally susceptible to SM-7338 and imipenem (76%). However, for one-third of the imipenem-resistant gram-negative bacilli (MICs, greater than 8 micrograms/ml), SM-7338 MICs were less than or equal to 4 micrograms/ml. Some endemic differences in patterns of SM-7338 activity against selected gram-negative species were found among some medical centers.

Anti-Bacterial Agents↗
PubMed1989

Clinical evaluation of a direct fluorescent monoclonal antibody test for detection of Pseudomonas aeruginosa in blood cultures.

A direct fluorescent monoclonal antibody test (DFA; Genetic Systems Corp., Seattle, Wash.) was evaluated for the detection of Pseudomonas aeruginosa in 178 blood culture broths obtained from 128 patients. The DFA identified 44 (98%) of 45 blood cultures positive for P. aeruginosa and was negative in 131 (98%) of 133 blood cultures which grew gram-negative rods other than P. aeruginosa. Upon further investigation, saline suspensions of the organism from the false-negative blood culture were strongly (4+) DFA positive. The false-positive reactions were not due to cross-reactivity, as shown by lack of DFA staining of the non-P. aeruginosa isolates following subculture to agar media. The specificity of the reagent was further demonstrated by directly staining culture isolates including 10 serotypes of P. aeruginosa (all positive) and 57 selected gram-negative bacilli including eight species of Pseudomonas that were not P. aeruginosa (all negative). DFA staining of blood culture broths was easy to perform and read with minimal background fluorescence. The DFA method can be performed in 50 min and appears promising as a rapid method for the identification of P. aeruginosa bacteremia.

Antibodies, Monoclonal↗