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Biomedical subjects

L D Saravolatz

Publications and source records attributed to L D Saravolatz.

At least 19 recordsLinked to original sources

Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection.

OBJECTIVE: To compare trimethoprim-sulfamethoxazole (TMP-SMZ) and vancomycin regarding efficacy and safety in the therapy of serious Staphylococcus aureus infections. DESIGN: Randomized, double-blind comparative trial. SETTING: A tertiary-care hospital. PATIENTS: One hundred and one intravenous drug users hospitalized with S. aureus infection. MEASUREMENTS: Cure and failure rates; blood and wound cultures; minimum inhibitory and bactericidal concentrations; serum inhibitory and bactericidal titers; temperature; leukocyte count; durations of treatment and hospitalization; and toxicity. RESULTS: Of 228 intravenous drug users, 101 had S. aureus infection and were included in the efficacy analysis (43 received TMP-SMZ and 58 received vancomycin). Methicillin-resistant S. aureus (MRSA) accounted for 47% of S. aureus isolates, and 65% of patients were bacteremic. Infections were cured in 57 of 58 vancomycin recipients and in 37 of 43 TMP-SMZ recipients (P less than 0.02). Failure occurred mostly in patients with tricuspid valve endocarditis and only in those with infection caused by methicillin-sensitive S. aureus (MSSA). The mean duration of bacteremia was 6.7 days in TMP-SMZ recipients and 4.3 days in vancomycin recipients. Among 222 subjects hospitalized for at least 24 hours, toxicity rates were similar for TMP-SMZ (23%) and vancomycin (20%) recipients; nausea and vomiting were associated with TMP-SMZ and inflammation at the intravenous site was associated with vancomycin. Forty-four percent of TMP-SMZ recipients and 29% of vancomycin recipients experienced side effects in the efficacy cohort (P greater than 0.05). CONCLUSIONS: Vancomycin is superior to TMP-SMZ in efficacy and safety when treating intravenous drug users who have staphylococcal infections. However, all treatment failures occurred in patients with MSSA infection at any site. Therefore, TMP-SMZ may be considered as an alternative to vancomycin in selected cases of MRSA infection.

Adult

The role of tumor necrosis factor in sepsis.

There is an increasing incidence of sepsis among hospitalized patients. Also, high mortality associated with sepsis and septic shock persists despite appropriate antibiotic therapy. Recent investigations have demonstrated that bacterial antigens stimulate a cascade of cellular mediators or cytokine release. In sepsis and septic shock the response of these cytokines often exceeds natural downregulation and leads to multisystem organ failure and even death in an unacceptably high number of patients. Many investigative studies have shown that tumor necrosis factor (TNF) is the prime mediator of the inflammatory response seen in sepsis and septic shock. Sepsis management in the future will include immune modulating therapy directed against the deleterious effects of cytokines, specifically TNF. This article reviews the current problem of sepsis and the evidence to support the role of TNF in sepsis. also, recent studies employing monoclonal antibodies against TNF as well as considerations for future studies are discussed.

Animals

Health care worker exposure to HIV-1 and HTLV I-II in critically ill, resuscitated emergency department patients.

STUDY OBJECTIVE: Exposure to HIV-1 is of profound concern to health care workers. HTLV-I and HTLV-II, retroviruses with similar modes of transmission as HIV-1, also cause disease in human beings. Emergency department resuscitations are high-risk situations for such exposure. The purpose was to determine the seroprevalence of HIV-1 and HTLV I-II in patients undergoing ED resuscitations, the magnitude of health care worker exposure, and risk factors associated with infection. DESIGN: Prospective identity-unlinked seroepidemiologic study. SETTING: ED of a 950-bed private inner-city teaching hospital. Participants included 370 patients undergoing ED resuscitations. MEASUREMENTS: Serum was tested for antibodies to HIV-1 and HTLV I-II. Questionnaires were completed by the physician in charge of the ED resuscitations. RESULTS: Fifteen (4.1%) (95% confidence interval [CI], 2.1% to 6.1%) patients were HIV-1 seropositive, and seven (1.9%) (95% CI, 0.7% to 3.1%) were HTLV I-II positive. Eleven (5.6%) (95% CI, 2.4% to 8.8%) of 197 trauma patients and 11 (6.4%) (95% CI, 2.8% to 10.0%) of 173 medical patients were infected with one of these viruses. Health care workers had direct cutaneous contact with patient blood during 114 (31%) ED resuscitations and with infected patient blood during 11 (3%) ED resuscitations. An additional 11 ED resuscitations involved parenteral exposures, one to HIV-1-infected blood. No factors could be identified that would quickly and reliably predict infection. CONCLUSION: Health care workers must protect themselves in such high-risk situations by strict compliance to mandatory universal precautions.

Adolescent

The emerging role of HTLV-I/II and HIV-1 among intravenous drug users in Detroit.

During 1987-1988, a seroprevalence study of the human immunodeficiency virus (HIV-1) and the human T-cell lymphoma/leukemia virus (HTLV-I/II) was performed among Detroit intravenous drug users unaffiliated with substance abuse programs. Seroprevalence data along with patient demographic information were compared to a similar study performed in 1985-1986. In the earlier study, 12 (12.5%) of 96 individuals tested positive for HIV-1. Of the 74 available negative samples retested in 1987-1988 for retroviruses, 7 (9.5%) tested positive for HTLV-I/II. Thus, the overall retroviral (HIV-1, HTLV-I/II) seropositive rate for 1985-1986 was 22%. In 1987-1988, 11 (15.7%) of 70 individuals tested positive for HIV-1 and 7 (10%) tested positive for HTLV-I/II. Concomitant infection with both viruses was found in 2 (2.9%) of the 70 individuals. Thus, retrovirus seroprevalence in 1987-1988 was 22.9%. In 1987-1988, significant differences between the retroviral-positive group and the retroviral-negative group consisted of intravenous drug use greater than 16 years (P = 0.059) for an odds ratio of 3.80 (CI 1.12-12.89) and sex with female prostitutes (P = 0.029) for an odds ratio of 5.38 (CI 1.38-20.95).

Adult

Safety, pharmacokinetics, and functional activity of human anti-Pseudomonas aeruginosa monoclonal antibodies in septic and nonseptic patients.

A mixture of five IgM human monoclonal antibodies (MAbs) against lipopolysaccharide antigens of Pseudomonas aeruginosa, plus a human IgG1 MAb against exotoxin A, were studied in 12 noninfected patients and 8 patients with P. aeruginosa bacteremia or pneumonia (or both). The preparation was well tolerated over a dose range of 0.3-1.2 ml/kg (0.75-3.0 mg/kg IgM protein). After a single infusion of 1.2 ml/kg (3.0 mg/kg IgM protein), serum antibody titers were boosted into therapeutic range, with serum half-lives ranging from 34 to 99 h. Also, opsonophagocytic activity in serum rose more than 1 log10 for all but one antibody. In no patient was an immunologic response against the MAb preparation detected.

Adult

Filtration of dialysate using an on-line dialysate filter.

UNLABELLED: Increased concerns about pyrogenic contamination of dialysate have led to the development of an on-line dialysate filtration system. Bacteriological testing of the system was performed (n = 6) by introducing bicarbonate concentrate contaminated with E. coli 026:B 6 (3 x 10(9) cfu/ml) into a dialysis machine equipped with a two-stage polysulfone filtration system. The bacterial concentration of the dialysate entering the filtration system was maintained above 10(6) cfu/ml and endotoxin levels ranged from 30-300 ng/ml during the 3-hour test period. Bacterial and endotoxin levels on the input side of the first-stage filter reached minimum concentrations of 5.4 x 10(9) cfu/ml and 30,000 ng/ml respectively. All output samples of filtered dialysate showed no bacterial growth and endotoxin levels were below the sensitivity (0.003 ng/ml) of the LAL assay. A dialysis machine (QD = 500), equipped with a single stage filtration system, was used for 18 months of clinical testing. In order to evaluate the system's reliability with regard to membrane failures and reduced dialysate flow, filter membrane integrity was verified weekly using a pressure holding test and dialysate flow was measured under routine clinical conditions. No membrane failures occurred, and dialysate flow was maintained at 511 +/- 17 ml/min (n = 70) during the test period. IN CONCLUSION: dialysate filtration is an effective and practical method for prevention of pyrogenic reactions due to high levels of bacteria and endotoxins.

Bacterial Infections

Reduction in Legionella pneumophila through heat flushing followed by continuous supplemental chlorination of hospital hot water.

An increase in endemic rate of nosocomial Legionella pneumophila pneumonia prompted an investigation that revealed 16.2% (12/74) of patient care hot-water sites surveyed were culture-positive for L. pneumophila. No positive cultures were recovered from cooling towers, air intakes, or construction areas. Heat flushing of hospital hot-water outlets to temperatures greater than 60 degrees C for 30 min achieved a 66% reduction in positive Legionella cultures. After 4 1/2 months, different serotypes recurred in previously eradicated areas and there were new positive cultures. Continuous supplemental chlorination of the hot-water system (2 parts per million [ppm]) significantly reduced the number of culture-positive samples from 37.4% (43/115) to 7.0% (8/115) after 6 weeks (P less than .005). Of 30 sites surveyed 6 months after hot-water chlorination, 67% (20) were still culture-negative. Of those positive, 70% had less than or equal to 150 L. pneumophila/ml and 90% were from bathtubs. Adverse effects of chlorination on users and plumbing have not been seen. There have been no definite cases of nosocomial L. pneumophila in areas served by supplemental chlorine during the first 17 months of the chlorination project. Technology allowing tighter regulation of chlorine and use of silicates to control corrosion have made continuous hot-water chlorination a safe and effective option in Legionella control.

Chlorine

Evaluation of the insulin jet injector as a potential source of infection.

In recent years jet injection of insulin has been widely used by patients with diabetes mellitus. Jet injectors may become contaminated by bacteria because of repeated use without cleaning; cleansing every 2 weeks is recommended. We investigated the occurrence of bacterial contamination by culturing jet injectors in everyday use by 19 patients with diabetes. Swabs from the interior chambers were cultured on blood agar plates. Only one of 20 cultures yielded bacterial growth, and the organism recovered was a presumed contaminant that could not be identified as any common pathogen. No study patient, nor any of more than 70 patients whom we instructed in jet injection, showed any clinical evidence of infection attributable to jet injector use. Jet injectors are unlikely to become colonized by bacteria or to cause infection in patients using them for insulin administration. The low rate of colonization may be due to the antibacterial preservatives added to commercial preparations of insulin. Additional data based on larger numbers of patients would be useful in further clarifying the risk of infection associated with jet injectors.

Adolescent

Infection surveillance in cardiac transplantation.

Infections are a major cause of morbidity and mortality in cardiac transplantation. There is little information describing screening and prospective surveillance of heart recipients. We describe a surveillance program that was used for 35 patients, which screens and follows recipients through serologic, virologic, and immunologic parameters. Pretransplantation surveillance identified four (11.4%) patients whose skin tests with purified protein derivative (PPD) were positive, one patient with giardiasis, and seven (20%) recipients who were susceptible to cytomegalovirus (CMV). Twelve (34.3%) patients had CMV infections, only one of which was primary and involved a seropositive donor. The low rate of primary infection (14%) may result from our use of CMV-negative blood products. Seven (20%) recipients who were seronegative for toxoplasmosis received seropositive hearts, and disseminated toxoplasmosis developed in one of them. Eight (22.8%) patients had asymptomatic significant increases in Epstein-Barr virus antibody titers, without evidence of lymphoma. Fifteen (42.8%) recipients had at least one herpes simplex virus reactivation. Preventive, diagnostic, and early therapeutic interventions should occur as a result of infection surveillance, thus leading to a reduced risk of infection during the period after cardiac transplantation.

Cross Infection

In-vitro susceptibility of staphylococci to fleroxacin in comparison with six other quinolones.

Susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA, n = 32), methicillin-sensitive S. aureus (MSSA, n = 32), and S. epidermidis (SE, n = 24) were determined to fleroxacin, amifloxacin, ciprofloxacin, difloxacin, enoxacin, norfloxacin, and ofloxacin. All organisms were isolated from the blood of patients with infective endocarditis. MRSA and MSSA MIC90s were less than 1.0 mg/l of fleroxacin, ciprofloxacin, difloxacin, and ofloxacin while amifloxacin and norfloxacin produced MIC90s of less than 2.0 mg/l and enoxacin MIC90s of less than 4.0 mg/l. For S. epidermidis MIC90s were less than 1.0 mg/l of all quinolones except amifloxacin whose MIC90 was less than 2.0 mg/l. Two strains from each staphylococcal group were used in time-kill trials performed with all seven quinolones. Within 8 h, all quinolones colony counts were decreased by one log. At 24 h, most quinolones decreased MRSA, MSSA, and SE colony counts by two to four logs; however, exceptions were found with (1) difloxacin, enoxacin, and norfloxacin against MRSA, (2) ciprofloxacin and enoxacin against MSSA, and (3) ciprofloxacin against SE in which all colony counts increased one to three logs in 24 h. When quinolone time-kill trials did not show a decrease in colony counts at 24 h, the MIC's for the 24 h growth showed a four- to 250-fold increase when compared with pre-trial MICs. No selection or emergence of resistant organisms was found with fleroxacin, amifloxacin or ofloxacin.

Anti-Infective Agents

Inhibition of Legionella pneumophila multiplication within human macrophages by fleroxacin.

The susceptibility of Legionella pneumophila to a new quinolone, fleroxacin, was studied in both an extra- and an intracellular system. The activity of fleroxacin was compared with that of erythromycin, cefoxitin, and rifampicin. In the extracellular system, erythromycin inhibited while cefoxitin killed the organism. Extracellularly, fleroxacin performed similarly to cefoxitin. Rifampicin was initially bactericidal for L. pneumophila but resistant bacteria emerged at 48 h. The Horwitz monocyte model was used for studies of intracellular antimicrobial activity. At ten times the MIC, cefoxitin did not inhibit intracellular L. pneumophila. Fleroxacin was as active as erythromycin and rifampicin in inhibiting intracellular L. pneumophila. No intracellular, rifampicin-resistant L. pneumophila emerged. Addition of rifampicin to cefoxotin, erythromycin or fleroxacin provided neither synergy nor antagonism.

Anti-Infective Agents

Medical management of osteomyelitis: considerations for home antibiotic chemotherapy.

Osteomyelitis can result from hematogenous seeding or contiguous infection, especially in association with impaired vascularity. Appropriate antibiotic therapy requires identification of the pathogen or pathogens and confirmation that the pathogens are susceptible to the antibiotic selected. Because of the long duration of parenteral antibiotic therapy required, treatment of osteomyelitis is expensive when patients are kept in the hospital for this reason alone. The development of long-half-life antibiotics that can be administered intramuscularly once a day and that are well tolerated has made outpatient parenteral therapy possible for many such patients. Cefonicid is a long-acting second-generation cephalosporin with activity against many of the microorganisms involved in osteomyelitis. Clinical studies have shown that cefonicid is effective and safe when used in an outpatient treatment program. Such programs have realized considerable savings over the cost of inpatient therapy.

Ambulatory Care

The in-vitro and in-vivo efficacy of cisplatin and analogues in the treatment of herpes simplex virus-II infections.

The antitumour effect of cisplatin results from cross-linking and disruption of DNA when it binds to DNA bases, especially cytosine and guanine. Since herpes simplex virus (HSV) has a high cytosine and guanine content, cisplatin might be expected to have an antiviral effect against HSV. The 50% inhibitory concentration of cisplatin for HSV-II was 0.06 mg/l. Six of ten platinum analogues had 50% inhibition of plaques at less than or equal to 10 mg/l. We evaluated the in-vivo activity of cisplatin against the MS strain of HSV-II in the mouse genital HSV model. Mice were treated either intraperitoneally or intravaginally beginning at 3 or 51 h after inoculation. In the intraperitoneally treated groups infection rates were lower, but not significantly; 4 of 15 in the 3-h and 7 of 15-h group, compared to 9 of 15 in the untreated control group (P greater than 0.18, chi-square test). Intravaginal cisplatin demonstrated a significant reduction of the infection rate from 10 of 15 untreated controls, compared to 5 of 18 in the 3-h and 5 of 17 in the 51-h group (P less than 0.05, chi-square test). No toxic effects of intravaginal cisplatin were seen in uninfected mice. These studies suggest that platinum containing drugs warrant further evaluation as a new class of antiviral agents with activity against HSV.

Animals

In-vitro susceptibility of gram-positive cocci to LY146032 teicoplanin, sodium fusidate, vancomycin, and rifampicin.

LY146032, a new antimicrobial agent with activity against Gram-positive cocci, was tested against methicillin-susceptible and methicillin-resistant Staphylococcus aureus, methicillin-susceptible and methicillin-resistant Staph. epidermidis, Staph. saprophyticus, and Streptococcus faecalis. MIC90s in cation-supplemented Mueller Hinton broth by the microdilution broth method were less than 1.0 mg/l for all organisms tested. Increasing or decreasing the inoculum size did not appreciably effect the MIC50 or MIC90 for any organism group nor did decreasing the incubation temperature. The addition of sodium chloride to the test system did not appreciably effect the susceptibility of methicillin-resistant Staph. aureus to LY146032. All organisms were 4 to 32 times more susceptible to LY146032 than to vancomycin. The Staph. aureus had LY146032 susceptibility patterns which were similar to those of teicoplanin and sodium fusidate. LY146032 was 4-16 times more active than teicoplanin against Staph. saprophyticus and Staph. epidermidis while teicoplanin was 8-16 times more active than LY146032 against Str. faecalis.

Anti-Bacterial Agents

In vitro susceptibility of gram-positive cocci to paldimycin.

Paldimycin (U-70138F) is a new antimicrobial agent with activity against gram-positive cocci. Clinical isolates of staphylococci and streptococci were tested. MICs were higher in Mueller-Hinton broth than in nutrient broth. Change in pH had minimal effect on the MICs in either broth. When inoculum size was varied, an inoculum effect was observed. The gram-positive cocci tested were generally more susceptible to paldimycin than to vancomycin.

Acetylcysteine