Candida species: emerging hospital bloodstream pathogens.
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Biomedical subjects
Publications and source records attributed to R P Wenzel.
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In 1986, an unusual syndrome of acute febrile cerebrovasculitis in the Piedmont Region of Virginia was reported. All patients had encephalopathy and prior exposure to both a sylvan environment and flea-infested animals. The initial serological studies suggested a rickettsial origin, corroborating clinical, epidemiological, and histopathological findings. Sera from four of five patients were subsequently studied by immunoblotting. Unabsorbed and absorbed sera were tested with electrophoresed and electroblotted Rickettsia typhi, Legionella bozemanii, and Proteus vulgaris OX19 antigens. The unabsorbed sera reacted with all three antigens. The P. vulgaris- and L. bozemanii-absorbed sera reacted with R. typhi only and without significantly less intensity. In contrast, the reactivity of R. typhi-absorbed sera was significantly lower with all three antigens. These results indicate that these patients had specific antibodies to a typhus group antigen. Although our findings suggest that a rickettsia of the typhus group may have caused this syndrome, no definitive diagnosis could be achieved because a rickettsial organism was not isolated.
An apparent single-source outbreak of Candida tropicalis sternal wound infections in eight patients was investigated by utilizing DNA restriction fragment analysis (RFA) with HindIII and BstNI. All eight outbreak isolates appeared to be identical and were easily differentiated from control isolates by DNA RFA. Compared with an arbitrarily selected reference outbreak isolate, greater than or equal to 95% of the bands in the restriction digests identified by a computerized image analysis system from each of the outbreak isolates were identical versus 13 to 53% of the bands in any of the nine control isolates. Outbreak strains were significantly more likely to match the reference outbreak isolate than were controls (P less than 0.0001). The RFA was greatly facilitated by the use of computerized image analysis and confirmed the epidemiologic link between a scrub nurse and the infected patients.
Two hundred seventy-five consecutive patients treated with bone marrow transplantation (BMT) during a 9-year interval were analyzed for the incidence and etiology of nosocomial pneumonia. Cases included adults who acquired pneumonia during the first hospitalization period within 100 days of the transplant. Fifty-five (20%) of the 275 patients developed nosocomial pneumonia, and the crude mortality during the hospitalization period was 74.5%. An etiology was established in 67.3% (37 of 55) of episodes. Thirty-six percent (20 of 55) of the cases were caused by Aspergillus species, either as the sole agent (15 patients) or in association with others. The crude mortality for patients with Aspergillus pneumonia was 95%. Elimination of 90% of Aspergillus cases in our unit would have the effect of reducing the overall attack rate of nosocomial pneumonia to 13.4% and the associated crude mortality to 43.4%.
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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.
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.
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To estimate the accuracy of routine hospital-wide surveillance for nosocomial infection, the authors performed a validation study at the University of Iowa Hospitals and Clinics, a 900-bed tertiary care institution, by daily concurrent surveys of all patients' charts. The study extended over a 10-month period from January to October 1987. The sensitivity and specificity of the reported data were 80.7% (95% confidence interval (CI) 72.2-89.2) and 97.5% (95% CI 96.4-98.5), respectively. The predictive values of positive or negative reports of an infection were 75.3% (95% CI 66.3-84.2) and 98.1% (95% CI 97.3-99.1), respectively. In a separate analysis, the data entry system was reviewed for eight descriptive variables among all patients with infections (n = 443) identified over a 2-month period. The data entry was found to be 94-99% accurate. To improve the efficiency of current surveillance, the authors used data gathered during the study to develop a computer model for the identification of patients with a high probability of having a nosocomial infection. The use of stepwise logistic regression identified five variables which independently predicted infection: age of the patient (years), days of antibiotics, days of hospitalization, and the number of days on which urine and/or wound cultures were obtained. Optimal sensitivity and specificity (81.6% and 72.5%, respectively) were found when the model examined patients with an 8% or higher a priori probability of infection; this figure corresponded to a review of 33% of the patients' charts. Increasing the a priori probability would progressively increase specificity and reduce both sensitivity and the number of charts needed for review. If it is prospectively validated, the model may provide a more efficient mechanism by which to conduct hospital-wide surveillance.
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.
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.
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.
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.
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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.