Tubulointerstitial nephritis due to a mutant polyomavirus BK virus strain, BKV(Cin), causing end-stage renal disease.

A renal biopsy from a 36-year-old man with AIDS showed a severe tubulointerstitial nephritis with intranuclear inclusions in epithelial cells. Electron microscopy revealed the characteristic findings of a polyomavirus (PyV) infection, and immunofluorescence indicated the presence of BK virus (BKV) antigen. Inoculation of rhesus monkey kidney cell cultures both with urine and with buffy coat blood cells resulted in a cytopathic response which was subsequently confirmed to be due to BKV. Further characterization of the viral DNA from the kidney by PCR amplification and Southern blot analysis with PyV and strain-specific primers and probes indicated that the virus was closely related to the BK(Dun) strain but different in its apparent sequence arrangement. Subsequent cycle sequencing showed a dinucleotide mutation of TG-->AA which substitutes hydrophilic Gln for hydrophobic Leu in a sequence homologous to an origin DNA-binding domain of simian virus 40 T antigen. It is suggested that the mutation and a coding region rearrangement of this strain of BKV designated BKV(Cin) has the potential to alter viral DNA replication and enhance pathogenicity.

Control of methicillin-resistant Staphylococcus aureus in a neonatal intensive-care unit: use of intensive microbiologic surveillance and mupirocin.

OBJECTIVE: To describe the epidemiology and the interventions used to control two methicillin-resistant Staphylococcus aureus (MRSA) epidemics involving 46 infants with two fatalities in a neonatal intensive care unit (NICU). SETTING: A 50-bed, level III NICU in a university hospital. INTERVENTIONS: After traditional interventions failed to stop the first epidemic, an intensive microbiologic surveillance (IMS) program was developed. Cultures were obtained on all infants each week, and those colonized with MRSA were isolated. When an infant was found to be colonized with MRSA, cultures immediately were obtained on all surrounding infants. This was continued until no MRSA-colonized infants were found in the area. During the first epidemic, mupirocin was used in an attempt to eradicate the organism from the unit. RESULTS: All infants, colonized and noncolonized, and parents of and personnel working with colonized infants were treated simultaneously with 5 days of mupirocin. This failed to eradicate MRSA in colonized infants. The spread of MRSA ceased in the unit, but a second epidemic occurred 4 months later. This time, IMS alone was successful in quickly containing the epidemic, and MRSA disappeared from the unit after all colonized infants were discharged. Plasmid analysis demonstrated that the same strain was responsible for both outbreaks. CONCLUSIONS: IMS and isolation are effective in containing the spread of MRSA in an NICU. The use of mupirocin failed to eradicate the organism.

The relationship between cytomegalovirus retrieved by bronchoalveolar lavage and mortality in patients with HIV.

STUDY OBJECTIVE: To evaluate mortality over 6 months of patients with HIV with cytomegalovirus (CMV) cultured from bronchoalveolar lavage (BAL) compared with those without CMV and to assess the significance of CMV cytologic study, CD4+ counts, and coexistent Pneumocystis carinii pneumonia. DESIGN: Retrospective evaluation of HIV-infected patients undergoing bronchoscopy with BAL. The 40 most recent HIV-positive patients undergoing bronchoscopy with BAL were included for each of three categories: CMV by cytologic study; CMV by culture only; and CMV absent. Patients for whom survival status at 6 months was unknown were excluded from analysis. SETTING: University hospital, tertiary care center. PATIENTS: Group 1 consisted of 36 patients with positive CMV culture and cytologic study and group 2 consisted of 38 patients with only a positive culture for CMV. Group 3 consisted of 40 patients with no evidence of CMV by BAL. RESULTS: On comparison of the groups, there was no difference in 3-week survival (from date of bronchoscopy). There was a statistically significant increase in mortality in group 1 patients compared with group 3 patients at both 3 and 6 months. Between groups 2 and 3, there was a difference in mortality that approached but did not reach significance at 3 months but did at 6 months. The mortality in group 1 at 3 months = 28%, at 6 months = 47%, whereas mortality in group 2 at 3 months = 26% and at 6 months = 45%. Group 3 had a 3-month mortality of 10% and a 6-month mortality of 15%. While those patients with positive CMV cytologic study had lower mean CD4+ counts, within the group, CD4+ counts were no different between the 3-month survivors and nonsurvivors (survivors, CD4/mm3 median = 38 [0 to 141]; and nonsurvivors, CD4/mm3 median = 16 [3 to 224]). Coinfection with P carinii did not increase mortality at 3 months. CONCLUSIONS: The CMV retrieved by BAL in HIV-infected patients was associated with significantly greater 3- and 6-month mortality. The CMV cytologic study did not predict a higher mortality and the difference in mortality between patients with and without CMV in BAL fluid was not directly attributed to lower CD4+ counts or P carinii coinfection.

Hepatitis C virus infection in healthcare workers: risk of exposure and infection.

OBJECTIVES: To determine the incidence of hepatitis C virus (HCV) infection among healthcare workers (HCWs) at a university hospital, the proportion of HCWs having non-A, non-B hepatitis (NANBH) who were anti-HCV positive, and the rate of HCV transmission following a HCV-positive needlestick injury. DESIGN: Longitudinal analysis of a dynamic (cohort) population. MEASUREMENTS: From 1980 through 1989, HCWs who had clinical NANBH were identified, and from 1987 through 1989, HCWs who reported a blood or body fluid exposure and the patients who were the source of the exposure were screened for antibodies to HCV. SETTING: A 732-bed, university hospital and outpatient clinics. RESULTS: Over the 10-year period, six cases of occupationally acquired NANBH were observed, for an incidence of 21 cases per 100,000 HCWs per year (standardized incidence ratio, 2.96; 95% confidence interval [CI95], 1.83 to 4.36). Four of the six cases were confirmed to be HCV infection. From 1987 through 1989, 176 (12.7%) of 1,387 patients who were the source of an exposure were anti-HCV positive. Exposures that occurred in the emergency department were more likely to be anti-HCV positive than were exposures from all other locations (relative risk [RR] = 1.7; P = 0.009). Of HCWs who had an HCV-positive needlestick injury and whose serum had been tested for anti-HCV at least 5 months after the exposure, 3 (6.0%) of 50 seroconverted. From 1987 through 1989, the incidence of HCV infection among HCWs was 54 cases per 100,000 HCWs per year. CONCLUSION: The incidence of clinical NANBH among HCWs in this study is approximately three times higher than that of non-HCWs. HCWs are at significant risk for exposure to and acquisition of HCV.

Recovery of viruses other than cytomegalovirus from bronchoalveolar lavage fluid.

STUDY DESIGN: To determine the yield and diagnostic significance of performing viral cultures on specimens obtained by bronchoalveolar lavage (BAL) in immunocompromised patients. DESIGN: Review of all BAL specimens submitted for viral culture over a six-year period. SETTING: Referral laboratory within a university hospital. The majority of specimens came from the university hospital, and for those cases, review of the patient's underlying disease, clinical presentation, and outcome was performed. PATIENTS: Over 95 percent of the patients had recognized underlying immunosuppression. INTERVENTION: None. MEASUREMENTS AND RESULTS: Cultures were done on 1,199 BAL specimens for viruses, and in 90 (8 percent), non-cytomegalovirus (CMV) viruses were recovered. These included herpes virus (53), influenza (11), parainfluenza (7), rhinovirus (12), adenovirus (5), enterovirus (1), and respiratory syncytial virus (1). Complete medical records were available for 1,020 (85 percent) of the BAL specimens, and the 77 patients with non-CMV viral pneumonia were studied in more detail. In 31 (40 percent) patients, virus was the only potential pathogen recovered. CONCLUSION: The recovery of respiratory viruses followed epidemic trends in the community and was often associated with self-limited illnesses without an increased mortality. The isolation of herpesvirus in patients without AIDS was associated with increased mortality in comparison with patients with AIDS (p < 0.01). This study demonstrates that viruses other than CMV may be recovered from BAL of patients with lower respiratory disease and may be the only pathogen recovered.

Recurrent epidemics caused by a single strain of erythromycin-resistant Staphylococcus aureus. The importance of molecular epidemiology.

OBJECTIVE--To compare the accuracy of clinical epidemiologic findings with results of molecular epidemiologic analysis in identifying the source of recurrent epidemics of erythromycin-resistant Staphylococcus aureus (ERSA) infections in a well-baby nursery. DESIGN--Epidemic investigations with retrospective and prospective microbiological surveillance. Staphylococcus aureus isolates were evaluated by plasmid analysis and genotyping. SETTING--A well-baby nursery in a 700-bed university teaching hospital with approximately 250 deliveries per month. PATIENTS--Newborn infants who developed ERSA infections during 1990 and 1991. INTERVENTION--Traditional infection control measures, including cohorting of infected infants and hand washing, were implemented. Personnel were cultured for nasal carriage of S aureus during both epidemics. Employees carrying ERSA were removed from the nursery and treated with mupirocin. RESULTS--In the first epidemic, 15 infants were infected with ERSA. A nursing assistant who cared for most of the infants was found to be a carrier of ERSA. She was removed from the nursery and the epidemic resolved. Fifteen months after the first epidemic ended, an epidemic that involved 11 infants began. The attending physician had a facial furuncle and was found to be a carrier of ERSA. The physician was treated and the epidemic resolved. Plasmid and genotyping showed the ERSA organisms from both epidemics were the same. The employee implicated in the first epidemic did not have the epidemic strain, but the physician who attended during both epidemics did. CONCLUSIONS--Traditional epidemic investigations may lead to false conclusions that can only be recognized with molecular epidemiologic techniques. For these techniques to be useful in the control of outbreaks, plasmid analysis and/or genotyping must be readily available.

Decline of clinical hepatitis B in workers at a general hospital: relation to increasing vaccine-induced immunity.

Hepatitis B is a well-recognized occupational hazard of health-care workers that can be prevented with vaccination. However, because data on the current epidemiology of hepatitis B virus (HBV) in this population are limited, no consensus exists regarding the requirement for immunization. In 1980-1989, 4,908 exposures of health-care workers to patients' blood and/or other body fluids were reported and evaluated at a general hospital. During this period, 4.8% of patients to whom health-care workers were exposed were positive for hepatitis B surface antigen (HBsAg). In exposed workers, the rate of protective immunity to HBV (measured by antibody to HBsAg) increased from 14% in 1980 to 55% in 1989. Hepatitis B vaccine became available at this hospital in 1983. The increase in antibody to HBsAg was not associated with an increase in antibody to HBV core antigen; this finding suggests that the increase in immunity was primarily vaccine induced. The incidence of reported clinical hepatitis B in health-care workers decreased from 82/100,000 in 1980-1984 to zero in 1985-1989 (odds ratio = 20.06; P = .0012). Thus, in this study, a program of hepatitis B immunization for health-care workers was associated with a significant decline in clinical HBV infection despite continued exposure to patients positive for HBsAg.

Yersinia enterocolitica infections in hospitalized patients: the problem of hospital-acquired infections.

OBJECTIVE: To study the epidemiology of Yersinia enterocolitica infections in hospitalized patients and to determine the frequency of hospital-acquired infection and the modes of transmission within the hospital. DESIGN: Descriptive study in which the clinical microbiology laboratory reported all positive Yersinia cultures to the infection control department; each case was investigated to determine the source of infection. SETTING: A 700-bed university teaching hospital. PARTICIPANTS: All patients who were culture-positive for Y enterocolitica after admission to the University of Cincinnati Hospital during the 4-year period between 1987 and 1990. RESULTS: Of 18 patients who were diagnosed with Yersinia infections, 8 (44%) were community-acquired. These patients were admitted with gastrointestinal symptoms and had their first positive cultures between days 1 and 5 of their hospitalizations. Five patients (28%) had hospital-acquired infections, having developed diarrhea after admission for unrelated problems, and became culture-positive between days 18 and 66. The remaining 5 patients could not be classified as either community- or hospital-acquired. These patients had gastrointestinal symptoms at the time of admission, but these could have been explained by other diseases. Their first positive stool cultures were not obtained until the second week or later during hospitalization, and 3 of these patients had negative stool cultures prior to a positive culture. CONCLUSIONS: Although Y enterocolitica has not previously been recognized as a common hospital problem, at least 28% of our patients acquired their Yersinia infections in the hospital. In some cases, cross infections, transmitted by healthcare workers, occurred between patients. Four of the 18 infections occurred in patients with acquired immunodeficiency syndrome.

Reemergence of epidemic methicillin-resistant Staphylococcus aureus in a general hospital associated with changing staphylococcal strains.

An epidemic of methicillin-resistant Staphylococcus aureus (MRSA) infections involving 323 patients occurred at the University of Cincinnati Hospital from 1977 to 1981. Subsequently, endemic MRSA persisted in the hospital for 6 years, until 1987, when a new epidemic began with 223 patients becoming infected over 3 years. Between the two epidemics, there was a major change in the MRSA recovered from infected patients, as demonstrated by three epidemiologic markers. Antibiograms showed that the tetracycline-resistant MRSA involved in the first epidemic was replaced by tetracycline-susceptible MRSA in the second epidemic; bacteriophage typing indicated that the original epidemic strain, D11/83A/85, had been replaced by new strains, many of which were susceptible to phage 54; and restriction endonuclease analysis of plasmid DNA confirmed that a single strain was involved in the first epidemic and that multiple strains were present in the second epidemic. The epidemiology of MRSA infections in the hospital changed with the change in staphylococcal strains. The first epidemic was hospital based with most infections occurring in surgical patients, and the burn unit was the major reservoir. In contrast, 28% of the patients in the second epidemic had community-acquired infections, and nursing home patients were an important source of these infections. Also, 29% of the hospital-acquired infections in this epidemic occurred in nonsurgical patients. This time the burn unit was not a reservoir of infection, but other intensive care units were. The increased diversity of strains of MRSA in the second epidemic might be related to increased transmission in the community and more widespread transmission in the hospital.

Isolation of human immunodeficiency virus type 1 in cutaneous blister fluid.

The human immunodeficiency virus type 1 (HIV-1) has been isolated from a number of body fluids, including semen, tears, cerebrospinal fluid, saliva, breast milk, alveolar fluid, and vaginal fluid, but it has not been isolated from fluid-containing skin lesions. We report the isolation of HIV-1 from cutaneous blister fluid in a patient with concomitant HIV-1 infection and porphyria cutanea tarda. Although transmission of HIV-1 through casual contact has not been reported, appropriate precautions should be taken to avoid direct contact with cutaneous fluid-containing lesions in HIV-1-positive patients.

Effect of educational programs, rigid sharps containers, and universal precautions on reported needlestick injuries in healthcare workers.

OBJECTIVE: To evaluate the effect of infection control programs on reported needlestick injuries in a general hospital. DESIGN: Surveillance of all reported needlestick injuries at the University of Cincinnati Hospital was maintained by the infection control department for five years, from 1985 through 1989. Data on individual workers were collected, tabulated on a monthly basis, and reviewed continually to monitor trends in injuries. During this time, the effects of each of three new infection control programs on reported injuries were evaluated sequentially. SETTING: A 700-bed general hospital that serves as the main teaching hospital of the University of Cincinnati. PARTICIPANTS: All employees of University Hospital who reported to personnel health for management of needlestick injuries. INTERVENTIONS: In 1986, an educational program to prevent injuries was initiated and continued throughout the surveillance period. In 1987, rigid sharps disposal containers were placed in all hospital rooms. In 1988, universal precautions were introduced with an intensive inservice. RESULTS: Surveillance identified 1,602 needlestick injuries (320/year) or 104/1,000/year. After the educational program began, reported injuries increased rather than decreased, and this was attributed to increased reporting. Subsequently, after installation of the new disposal containers, reported injuries returned to the levels seen prior to the educational program, but recapping injuries showed a significant decrease from 63/year to 30, or 20/1,000/year to 10. This decrease was observed in nurses but not in other healthcare workers. After universal precautions were instituted, total injuries increased slightly, but recapping injuries remained at 50% of the levels reported prior to the use of rigid sharps disposal containers. CONCLUSIONS: The three infection control programs failed to produce a major reduction in reported needlestick injuries, except for a decrease in recapping injuries associated with the placement of rigid sharps disposal containers in all patient rooms. These observations indicate that new approaches are needed to reduce needlestick injuries.

Emergence of acyclovir-resistant varicella zoster virus in an AIDS patient on prolonged acyclovir therapy.

We demonstrate for the first time the appearance of acyclovir resistance in serial varicella zoster isolates from a patient treated with acyclovir. We recovered varicella zoster virus three times over a period of 5 months from the skin lesions of this patient with AIDS who was treated with three courses of intravenous acyclovir and prolonged low-dose oral acyclovir. The isolate recovered from a typical zoster lesion before acyclovir, and one obtained from a hyperkeratotic lesion 2 months later, after intravenous and oral acyclovir, were sensitive to acyclovir and produced normal amounts of thymidine kinase. In contrast, virus recovered from lesions 5 months after the onset, when the patient had received repeated courses of acyclovir, was acyclovir-resistant and thymidine-kinase-deficient. Resistance to acyclovir was associated with persistence of lesions which failed to improve with intravenous acyclovir, but was not associated with new lesion formation.

Cytomegalovirus in the bronchoalveolar lavage fluid of patients with AIDS.

This study investigated the significance of detecting cytomegalovirus in the bronchoalveolar lavage fluid of patients with human immunodeficiency virus infection. Bronchoscopy with BAL was performed on all patients. Lavage was examined for CMV by cytology, culture, and immunofluorescence. The lavage results were compared to clinical status at the time of bronchoscopy and the outcome of the respiratory event. Cytomegalovirus was detected in 51 percent of the BALs in the patients with HIV infection and 25 percent of the immunosuppressed patients without HIV. No association was found in the HIV infected patients between CMV and hypoxemia, abnormal chest roentgenogram, leukopenia, and increased mortality. As indicated by mortality, CMV did not significantly increase the severity of Pneumocystis carinii pneumonia. The study also suggested that CMV in BAL fluid reflected bronchopulmonary replication of the virus, and not contamination by virus in the blood. Cytomegalovirus does not appear to contribute directly to the pulmonary disease found in most patients with HIV infection.

Comparison of histologic nodal reactive patterns, cell suspension immunophenotypic data, and HIV status.

While cell suspension immunophenotypic studies are widely used as an aid in the diagnosis and classification of lymphomas and leukemias, much less attention has been directed toward interpretation of the results in reactive lymphoid proliferations. Cell suspension immunophenotypic data were therefore analyzed for 119 lymph nodes with reactive lymphoid proliferations which were divided into five major histologic categories: follicular hyperplasia, marked (FH,M), or moderate (FH); dermatopathic lymphadenopathy (DL); diffuse hyperplasia (DH); or "other." With the aid of a computer-assisted morphometer, the following were also measured and calculated: proportion of node occupied by follicles, mean relative follicle size, and mean follicle shape factor. Finally, in 57 cases, the influence of human immunodeficiency (HIV) status on the findings was analyzed. Although individual cases varied widely, cases of DL had significantly more CD3+ (T) cells, higher CD4:CD8 ratios, and fewer CD19+ (B) cells than other categories. Cases of FH,M had significantly lower CD4:CD8 ratios and more CD19+, CD10+, and transferrin receptor positive cells. Cases of FH,M and FH known to be HIV-negative had higher CD4:CD8 ratios than the HIV-positive cases. Peripheral blood CD4:CD8 ratios performed in 38 patients showed a strong correlation with nodal ratios. Morphometric data supported the correlation between follicular hyperplasia and increased proportions of CD19+, CD10+, and transferrin receptor-positive cells. Rare cases had CD5:CD2 or CD3 ratios of greater than 1 or "monoclonal" kappa to lambda ratios. CD4:CD8 ratios varied widely, but aberrant T cell phenotypes were not identified. These studies demonstrate that, although great variation exists, there are certain associations between types of reactive lymphoid hyperplasia and cell suspension immunophenotypic findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery of human immunodeficiency virus and detection of p24 antigen in bronchoalveolar lavage fluid from adult patients with AIDS.

Published reports indicate that HIV is recovered from BAL fluid of patients with AIDS who have LIP but not with other AIDS-related pulmonary disease. Our experience has been different. Ten BAL specimens from nine patients with AIDS were cultured directly in peripheral blood mononuclear cells, and all ten cultures were positive for HIV as indicated by examination of the culture supernatant by reverse transcriptase assay and enzyme immunoassay for HIV antigen. Five of the specimens were also positive for Pneumocystis carinii, and other pulmonary diagnoses included histoplasmosis, lymphoma, Kaposi's sarcoma, and aspiration pneumonia. Five additional BAL specimens were cultured after freezing at -70 degrees C, but only two were culture-positive for HIV (p = 0.022; FET). This study indicates that HIV can be recovered from the BAL fluid in most patients with AIDS, unrelated to the type of pulmonary disease. In contrast to cultures, HIV antigen was detected in the BAL fluid of only one patient, and that patient had LIP with noncaseating granulomas. Therefore, HIV culture is not useful in the diagnosis of LIP, but HIV antigen detection should be studied further. All BAL fluids should be considered potentially infectious.

Acute febrile cerebrovasculitis. A non-spotted fever group rickettsial disease.

In December 1985, a patient was seen with an illness that was clinically compatible with the recently described clinical syndrome of acute febrile cerebrovasculitis, including fever, headache, altered mentation, multifocal neurologic signs, and cerebrospinal fluid pleocytosis. An extensive medical evaluation failed to reveal a cause, until, retrospectively, she was shown to have antibodies to Rickettsia typhi. Detailed serologic analysis with enzyme immunoassays and protein immunoblots indicated that she was infected with a non-spotted fever group Rickettsia, most likely either R typhi or Rickettsia canada. Serum samples from a mouse trapped at her home contained antibody only to R canada. Evaluation of patients with acute febrile cerebrovasculitis in the future should include rickettsial blood cultures to attempt specific identification of the species involved.