Biomedical subjects
Publications and source records attributed to J R Lentino.
Urea and creatinine levels in spent hemodialysates showed only small declines in spite of incubation at 37 degrees C for 36 hours. In the determination of dialysate-side solute removal, it would seem prudent to keep spent dialysate cold during collection to retard bacterial breakdown of these waste products.
Exposure to GB virus C (GBV-C) was determined in several U.S. populations by both reverse-transcription-polymerase chain reaction (RT-PCR) and by an enzyme linked immunosorbent assay (ELISA) for antibodies to mammalian cell-expressed GBV-C envelope protein, E2 (GBV-C E2). Most individuals exposed to GBV-C were either RNA positive/ELISA negative or ELISA positive/RNA negative. Exposure, therefore, was measured as the sum of GBV-C RNA positive and GBV-C E2 antibody positive specimens, and was higher in commercial plasmapheresis donors (40.5%) than in volunteer blood donors (5.5%). In intravenous drug users (IVDUs), GBV-C exposure was 89.2%. Serial bleed specimens tested for GBV-C RNA indicate that some patients remain viremic for at least 3 years and fail to produce detectable antibodies to GBV-C E2. In other exposed individuals who tested negative for GBV-C RNA, antibodies to E2 appear to be similarly long-lived (greater than 3 years) with a fairly constant titer (ranging in reciprocal endpoint dilution from 336 to 21,504). Since the detection of GBV-C RNA and GBV-C E2 antibody are mutually exclusive in most exposed individuals, studies pertaining to incidence and prevalence of GBV-C infection require both antibody and nucleic acid detection.
Among the three recently described GB viruses (GBV-A, GBV-B, and GBV-C), only GBV-C has been linked to cryptogenic hepatitis in man. Because of the limited utility of currently available research tests to determine antibody response to GBV-C proteins, the prevalence of GBV-C RNA in human sera was studied using reverse transcription-polymerase chain reaction (RT-PCR). The prevalence of GBV-C is higher among volunteer blood donors with elevated serum alanine aminotransferase (ALT) levels (3.9%) than among volunteer blood donors with normal ALT levels (0.8%). Higher rates were also noted among commercial blood donors (12.9%) and intravenous drug users (16.0%). GBV-C was frequently detected in residents of West Africa, where the prevalence was > 10% in most age groups. Approximately 20% of patients diagnosed with either acute or chronic hepatitis C virus (HCV) were found to be positive for GBV-C RNA. In addition, GBV-C RNA sequences were detected in individuals diagnosed with non-A-E hepatitis, with clinical courses ranging from mild disease to fulminant hepatitis. Fourteen of sixteen subjects with or without clinically apparent hepatitis were positive for GBV-C RNA more than 1 year after the initial positive result.
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The synergistic activity of levofloxacin and oxacillin against levofloxacin-resistant isolates of methicillin-resistant Staphylococcus aureus was tested by the time-kill method. The combination of levofloxacin at 1/4 the MIC for the isolate plus oxacillin at 8 micrograms/ml (< 1/4 the MIC) was synergistic against seven of nine isolates at 8 h, although no significant synergy was demonstrated at 24 h. This combination may prove to be effective against multidrug-resistant methicillin-resistant S. aureus, and further studies are warranted.
A randomized, controlled clinical trial was performed to determine whether individualized dosing by use of Bayesian pharmacokinetic modeling could decrease nephrotoxicity accosted with aminoglycoside therapy. Two hundred forty-three patients receiving aminoglycosides for suspected or proven infection were randomly assigned to one of three groups: usual physician-directed dosing (Group 1), pharmacist-assisted dosing (Group 2), or pharmacist-directed dosing (Group 3). Dosing in Groups 2 and 3 was based on a Bayesian pharmacokinetic dosing program, whereas Group 1 served as the control group. Individualized dosing resulted in higher mean postinfusion (peak) serum aminoglycoside levels, higher ratios of mean peak level to minimum inhibitory concentration (peak/MIC ratios), and a trend toward lower trough serum levels. Milligrams per dose were higher and number of doses per day was lower in the pharmacist-dosed groups. However, the incidence of nephrotoxicity (> or = 100% increase in serum creatinine) was not different among the three groups (16, 27, and 16% in Groups 1, 2, and 3, respectively). Similarly, severity of toxicity was not affected by the dosing intervention. Risk factors for toxicity included duration of therapy, shock, treatment with furosemide, older age, and liver disease. After controlling for these factors, the dosing intervention still had no effect on nephrotoxicity. It was concluded that Bayesian pharmacokinetic dosing did not decrease the risk of nephrotoxicity associated with aminoglycoside therapy.
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We evaluated the safety and efficacy of ofloxacin administered both by the intravenous route and orally in 26 men with serious skin and soft tissue infection. Twenty-one patients completed antimicrobial therapy and were fully evaluable. Of these, 18 were judged to be cured, while 3 failed therapy either during or within 2 weeks after completion of therapy. Overall, Staphylococcus aureus was the most commonly isolated pathogen and was found to be susceptible to ofloxacin in 12 of 14 patients. Two patients, 1 with a tolerant isolate of S. aureus, the other patient with a resistant isolate of S. aureus, responded clinically to ofloxacin therapy; a third patient with an initially ofloxacin-sensitive isolate failed therapy, and on subsequent culture an ofloxacin-resistant S. aureus was isolated. Ofloxacin was well tolerated and efficacious in the treatment of skin and soft tissue infections including those caused by staphylococci and streptococci.
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We surveyed for serologic evidence of either HIV-1 or HTLV-I/II infection in 387 male veterans who entered into an inpatient drug treatment center. Serum was obtained after receiving written informed consent. Serum specimens were tested by enzyme-linked immunosorbent assay for antibody to HIV-1 and for antibody to HTLV-I/II; sera that were repeatedly reactive were then tested by Western blot (HIV-1/HTLV-I/II) and radioimmunoprecipitation assay (HTLV-I/II). Sixty-five of 387 (16.79%) patients were tested and confirmed as positive for HTLV-I/II only antibodies and 30 of the 387 (7.75%) were positive for HIV-1 only antibodies. An additional nine patients (2.32%) were seropositive for antibodies to both viruses. A statistically significant difference in the CD4/CD8 lymphocyte ratio was associated with HIV-1 seropositivity. HTLV-I/II seropositivity was strongly associated with black race, age, and duration of i.v. drug use, but not with sexual intercourse as determined by lifetime history of number of sexual partners, incidence of sexually transmitted diseases, type of drug used, or needle-sharing practices.
We compared the activity of daptomycin, vancomycin and fluoroquinolones against 46 blood isolates of Staphylococcus epidermidis. Daptomycin was more rapidly bactericidal than vancomycin and demonstrated less of an inoculum effect than the quinolones. Time-kill kinetic studies demonstrated no significant differences in survival in broth as compared to 50% human serum-supplemented broth. Daptomycin and the quinolones are suitable for study in clinical trials of efficacy as therapeutic alternatives to vancomycin for S. epidermidis infections.
An outbreak of influenza A/Philippines H3N2 at a 1156-bed Veterans Administration Hospital involved 118 hospital personnel and 49 patients. Prospective surveillance methods that had been established within the hospital were not useful in identifying the number of involved individuals. Community indicators of influenza, which were reviewed retrospectively, would not have identified circulating influenza in this population. Control of the outbreak was accomplished using a creative approach that immunized over a third of the physician and nursing staff. This immunization program was successfully used in subsequent years to increase personnel compliance with the Immunization Practices Advisory Committee recommendations to annually immunize hospital personnel.
Methicillin and gentamicin resistant strains of Staphylococcus aureus (MRSA) remains a cause of significant morbidity and mortality. Vancomycin is usually effective against these strains, but toxicity and expense are significant drawbacks. Resistance to the new quinolones has been demonstrated in vitro and during clinical therapeutic trials. Trimethoprim-sulphamethoxazole has proved to be effective in vitro against staphylococcal strains that are resistant to gentamicin, methicillin, and quinolones. As determined by time-kill kinetic studies, trimethoprim-sulphamethoxazole was rapidly bactericidal. Clinical evaluation of trimethoprim-sulphamethoxazole against MRSA in patients with osteomyelitis is under study. We believe that our data support the use of trimethoprim-sulphamethoxazole as a potentially economical and effective alternative for the treatment of infections caused by MRSA.
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Establishment of the microbiological etiology of bacterial pneumonia by sputum culture is confounded by both lack of recovery of fastidious pathogens and contamination of specimens with oropharyngeal flora. We reviewed the clinical records from 249 patients over a 3-month period for evidence of pneumonia. Gram staining and cultures were performed on 381 specimens isolated from this population of patients. Recovery of respiratory tract pathogens was accomplished with 354 specimens from 226 patients; 27 specimens yielded normal flora in culture but were smear positive. An additional 256 specimens submitted to our microbiology laboratory did not meet smear criteria for purulence nor did they yield respiratory tract pathogens in culture. A total of 637 specimens submitted to the microbiology laboratory were evaluated for sputum purulence by the criteria of Bartlett. Of the total 354 specimens which were positive in culture for a pathogen, 182 (52%) were submitted from 150 patients with no objective evidence of pneumonia. The majority of specimens obtained from patients without pneumonia were nonpurulent. However, 71 of 182 culture-positive specimens obtained from 50 patients without pneumonia were purulent. Approximately half of these patients (31 of 50) had other pulmonary or upper respiratory tract pathology which could account for the sputum purulence. Among the 172 culture-positive specimens from 76 patients with pneumonia, only 100 (58%) were acceptable by smear criteria. An additional 23 patients provided expectorated purulent sputum from which no respiratory tract pathogen could be isolated. Of these 23, 7 had pneumonia. We conclude that sputum culture and Gram staining are neither specific nor sensitive as diagnostic tools. Objective criteria for purulence of Gram-stained specimens must be applied before their inoculation into culture media. Specimens should be sought only from patients with objective evidence of pneumonia.
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