Biomedical subjects
Publications and source records attributed to R A Salata.
Resistance to linezolid has been associated with a G2576U mutation in domain V of the 23S rRNA. We analyzed nine clinical isolates of linezolid-resistant enterococci and showed a clear association between the number of 23S rRNA genes containing this mutation and the level of linezolid resistance expressed.
The innate cellular immune (iCMI) system provides for the rapid production of interferon-gamma (IFN gamma) by NK cells in response to microbial threats. In this review, we examine the cellular and cytokine mechanisms of innate cellular immunity as determined in murine endotoxemia. This will be contrasted to the subsequent suppression of these same responses present in the mouse model of endotoxin tolerance, which is characterized by profound deficiency in both IL-12 and IFN gamma synthesis. Transient IFN gamma deficiency due to altered iCMI function has also been described in trauma or burn patients and is termed "clinical immune paralysis." If the common pathogenesis of these entities can be better understood, immune-based interventions might be identified for restoring iCMI function. In addition to the gain in basic immunologic insight, research on this subject may deliver future forms of prophylaxis against infection that do not rely on antibiotics and that will not promote antimicrobial resistance.
We analyzed the deaths in an outpatient human immunodeficiency virus (HIV) care clinic at University Hospitals in Cleveland from January 1995 through December 1999. The number of annual deaths decreased progressively, from 112 in 1995 to 32 in 1999. The median final CD4(+) cell count before death increased progressively from 10 cells/microL in 1995 to 90 cells/microL in 1999 (P<.01); 20%--25% of patients who died from 1997 through 1999 had plasma HIV RNA levels below detection limits. From 1995 through 1998, deaths due to infection, to end-stage acquired immune deficiency syndrome, and to malignancies decreased, whereas the proportion of deaths due to end-organ failures and of uncertain relationship to HIV infection increased. The spectrum of mortality in HIV disease has changed recently; although opportunistic infections cause death less frequently, deaths are occurring in people who have control of HIV replication and with some preservation of immune function. These observations underscore the need to monitor the etiologies of HIV-associated mortality and to better our understanding of the relationships among immune defenses, treatment-related toxicities, and end-organ failure in patients with HIV disease.
We report our experience with linezolid in an investigation of its use against resistant gram-positive bacterial infections. Fifteen patients who had renal failure (n=6), recent liver transplantation (n=5) or surgery (n=6), cancer (n=3), endocarditis (n=2), or human immunodeficiency virus infection (n=1), along with infections due to vancomycin-resistant enterococcus (VRE), and 2 patients with infections due to methicillin-resistant Staphylococcus species who had adverse reactions to vancomycin were treated with linezolid (600 mg every 12 h for 5-42 days (mean+/-SD, 20.5+/-3.5 days). Abscess drainage or prosthetic device removal was undertaken. Microbiological cure occurred in all 10 patients who completed therapy, and all 7 patients alive at follow-up were free of infection. No deaths were attributable to the index infection. Adverse events associated with linezolid use were mild leukopenia in 1 patient and nausea in another. It appears that administration of linezolid, in conjunction with surgical intervention or device removal, is an effective treatment option for serious resistant gram-positive bacterial infections.
We studied the molecular epidemiology of vancomycin-resistant enterococci (VRE) isolated in northeast Ohio during 1996 and examined the association between isolation of VRE from samples other than stool and antimicrobial purchases for five Cleveland hospitals. Susceptibility testing and pulsed-field gel electrophoresis were used to analyze 363 isolates from individual patients from 13 hospitals. Susceptibility testing indicated that 287 strains (79%) expressed the VanB phenotype and 76 (21%) expressed the VanA phenotype. The outbreak was polyclonal, with 30 total genotypes. Both VanA and VanB VRE demonstrated multiple genotypes. One genotype was present in all hospitals, suggesting spread between hospitals. For five teaching hospitals, rates of isolation from non-stool sources and from blood correlated positively with purchases of ticarcillin/clavulanic acid (P = .005). In summary, this outbreak demonstrates transmission of VRE between several hospitals in a geographic region and suggests that use of certain beta-lactam antibiotics may be associated with an increased prevalence of VRE.
Histoplasma capsulatum is a dimorphic fungus with the mycelial form producing spores that are readily airborne and able to reach small bronchi and alveoli. Isolation of the mycelial form of H. capsulatum in nature shows a striking correlation with moist, acidic soils, frequently contaminated with bird or bat excreta. Bats, but not birds, may be infected by H. capsulatum and may excrete the fungus in their feces. Skin test surveys show that the infectious agent is present worldwide in the areas between 45 degrees north and 30 degrees south of the equator. Clusters of cases may occur because of the disturbance of soil contaminated with H. capsulatum, or by visiting bat caves. Cave-associated histoplasmosis has been reported from the Americas, Africa, Oceania, and Africa. Recently, cave-associated histoplasmosis has been reported in travelers returning from Costa Rica and Peru. We report a cluster of cave-associated acute histoplasmosis that occurred in college students returning from Ecuador. Advice regarding histoplasmosis prevention should be given to travelers planning to visit bat-infested caves, and histoplasmosis should be considered in the differential diagnosis of febrile illness in returning travelers with a history of epidemiologic or geographic exposure.
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BACKGROUND: Clostridium difficile colitis in the cancer patient receiving chemotherapy is a frequent cause of morbidity which may prolong hospitalization. Techniques for identifying infection often delay the initiation of therapy. PATIENTS AND METHODS: In this retrospective case-control analysis, we identified predictors for C. difficile-associated diarrhea in 29 patients hospitalized from 1988 to 1993 on a hematologic malignancy/bone marrow transplant unit (hospital A). We then validated our model with 58 C. difficile cases and 74 controls admitted to an oncology unit from a different institution (hospital B). RESULTS: We found that low intensity of chemotherapy (P < 0.001), lack of parenteral vancomycin use (P = 0.03) and hospitalization within the past two months (P = 0.05) were independently predictive of C. difficile colitis by multivariate analysis. These variables were weighted for predictive capability using a receiver operator characteristic score; low intensity chemotherapy was assigned two points, lack of parenteral vancomycin received one point and prior hospitalization one point (P < 0.001 by chi 2 for trend). The receiver operating characteristic (ROC) curve areas were 0.78 for patients at hospital A and 0.70 at hospital B indicating moderate drop off in discrimination. Compared to hospital A patients, hospital B patients hospitalized between 1989 and 1994 were more often women (P = 0.04), received less systemic vancomycin (P = 0.01), were less frequently neutropenic (P < 0.05), and received less intense chemotherapy regimens (P < 0.05). Despite these differences in demographics in patients between these institutions, our predictive model was validated in hospital B patients (P = 0.02 by chi 2 for trend). CONCLUSIONS: The results of this study may help clinicians predict the risk of C. difficile disease in the hospitalized immunocompromised oncology patient and may help guide empiric therapy while awaiting results of stool toxin assays.
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The primary care physician is faced with a bewildering array of new oral antimicrobials to treat common infections. These agents promise to be extremely effective as replacements for time-honored drugs, as prophylaxis, and for the treatment of infections previously requiring prolonged intravenous therapy. The overuse of the newer macrolides, quinolones, and beta-lactam beta-lactamase inhibitors may prove to be ecologically and economically costly. It is feared that the selective pressure from these broad spectrum agents may burden society with an even greater problem of multiply resistant community-acquired pathogens. The specific therapeutic and economic advantages and disadvantages of each class should be considered and the decision to employ these agents should be highly individualized.
Renal disease in patients infected with human immunodeficiency virus (HIV) often presents with significant proteinuria and progressive renal failure; focal glomerulosclerosis is the most common renal pathology identified. To our knowledge, we report the first case of nephrotic-range proteinuria and preserved renal function in an HIV-infected patient in association with disseminated histoplasmosis. The initial level of proteinuria was 12.5 g/24 h. The patient developed a concomitant lesion on his neck, which was biopsied and identified as Histoplasma capsulatum by fungal stains and culture. The serum CF titer of antibody against yeast antigens of H. capsulatum was 1:8. The level of serum albumin decreased to 2.0 g/dL, and the level of serum cholesterol increased to 284 mg/dL. Immunohistochemical staining of renal biopsy tissue demonstrated immune complexes within the mesangium; H. capsulatum antigen was also demonstrated in the mesangium. Therapy with oral itraconazole resulted in marked clinical improvement. The findings in this case emphasize the need to rule out treatable causes of the nephrotic syndrome in AIDS, especially in cases of immune-complex glomerulonephritis.
Pityriasis rubra pilaris is an uncommon hyperkeratotic, papulosquamous disorder that has been reported in patients infected by HIV. We recount a case of pityriasis rubra pilaris in an HIV-seropositive man. A 36-year-old man with a history of ulcerative colitis and recurrent otitis externa had diffuse psoriaform erythroderma. He was treated initially with methotrexate and isoretinoin without clinical improvement. Skin examination showed large, erythematous, orange, scaly patches on the upper extremities and thickening of the nail beds. The palms and soles were hyperkeratotic. Skin biopsy revealed changes that were consistent with pityriasis rubra pilaris. Six months before the onset of symptoms, results of an enzyme-linked immunosorbent assay (ELISA) and Western Blot assay for HIV were negative. Six months after symptoms, results of repeat enzyme-linked immunosorbent assay and Western blots for HIV were positive (CD4+ T-cell count = 200 cells/ mm3). Clinical course had been complicated by episodes of Staphylococcus aureus bacteremia, mucocutaneous candidiasis, and development of localized squamous cell carcinoma of the skin. The increased severity of pityriasis rubra pilaris should prompt clinicians to consider coinfection with HIV in patients who have disease that is refractory to treatment. Clinicians also should remain vigilant for the development of squamous cell carcinoma.
PURPOSE: To determine if prednisone ameliorates the course of human immunodeficiency virus-associated nephropathy (HIV-AN). PATIENTS AND METHODS: Twenty consecutive HIV-infected adults with biopsy-proven HIV-AN (n = 17) or clinical characteristics of HIV-AN (n = 3) with serum creatinine concentrations > 177 mumol/L (2 mg/dL) or proteinuria > 2.0 g/d or both were prospectively evaluated and treated with prednisone at a dose of 60 mg/d for 2 to 11 weeks, followed by a tapering course of prednisone over a 2- to 26-week period. Serum creatinine concentration, 24-hour protein excretion, serum albumin, and steroid-related adverse effects were assessed before and after treatment. RESULTS: Nineteen patients had serum creatinine concentrations > 117 mumol/L (2 mg/dL). Two of them progressed to end stage renal disease (ESRD) in 4 to 5 weeks. In 17 patients serum creatinine levels decreased from 717 +/- 103 mumol/L (8.1 +/- mg/dL) (mean +/- SE) to 262 +/- 31 mumol/L (3.0 +/- 0.4 mg/dL) (P < 0.001). Five patients relapsed after prednisone was discontinued and were retreated. In these 5 the serum creatinine declined from 728 +/- 107 mumol/L (8.2 +/- 1.2 mg/dL) to 344 +/- 47 mumol/L (3.9 +/- 0.5 mg/dL) (P < 0.01) in response to the second course of prednisone. Twelve of 13 tested patients showed a reduction in 24-hour urinary protein excretion with an average decrement from 9.1 +/- 1.8 g/d to 3.2 +/- 0.6 g/d (P < 0.005). Serum albumin increased from 24.4 +/- 3.6 g/L to 29.3 +/- 2.6 g/L (P = NS) in the 11 patients with paired 24-hour urine collections for whom pre- and post-treatment determinations were available. In one non-azotemic patient with nephrotic syndrome, protein excretion declined from 15.2 to 2.2 g/day and the serum albumin increased from 4.0 g/L to 31.0 g/L. The 20 patients have been followed for a median of 44 weeks (range 8 to 107). Eight ultimately required maintenance dialysis. Eleven died from complications of HIV disease 14 to 107 weeks after institution of prednisone; none was receiving prednisone at the time of death. Seven are alive and free from ESRD a median of 25 weeks (range 8 to 81) from the initiation of prednisone therapy. Six patients developed a total of seven serious infections while receiving prednisone, including Mycobacterium avium-complex infection in 2 and CMV retinitis in 3. CONCLUSION: Prednisone improves serum creatinine and proteinuria in a substantial proportion of adults with HIV-AN. Corticosteroid-related side effects are not prohibitive. A prospective, randomized controlled trial is required to confirm these preliminary results.
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OBJECTIVES: Although Clostridium difficile is a common pathogen in hospitalized patients with diarrhea, no study has attempted to develop a predictive model to estimate the likelihood of C. difficile positivity. METHODS: We conducted a cross-sectional study at a single hospital of 271 patients with diarrhea for whom stool was tested for C. difficile toxin. The sample was randomly divided into a subset to derive the model (n = 180) and another to validate it (n =91), and independent predictors of toxin positivity were identified using logistical regression analysis. RESULTS: C. difficile toxin was present in 81 patients and absent in 190. In the derivation set, a positive toxin was independently predicted (p < 0.0005) by readmission within 2 wk of prior hospitalization, by a white blood cell count > or = 10,000/mm3, and by presence of fecal leukocytes. In the validation set, C. difficile toxin was present in 24, 29, and 77% of patients with 0, 1, and > or = 2 risk factors, respectively. CONCLUSION: If validated prospectively and/or other centers, the model could identify patients who should be considered for empirical management while awaiting results of toxin assays.