Biomedical subjects
Publications and source records attributed to D Rimland.
The Association for Professionals in Infection Control and Epidemiology, Inc (APIC), is a multidisciplinary, voluntary, international organization of professionals who practice infection control and the application of epidemiology in all health settings. APIC is an international leader in prevention and control of infection transmission.
The Association for Professionals in Infection Control and Epidemiology, Inc (APIC) is a multidisciplinary, voluntary, international organization of professionals who practice infection control and the application of epidemiology in all health settings. APIC is an international leader in prevention and control of infection transmission.
OBJECTIVE: To determine the role of mucositis severity in the development of vancomycin-resistant enterococcal (VRE) bloodstream infection (BSI). SETTING: A tertiary-care university medical center. PARTICIPANTS: Hematology-oncology-unit inpatients. DESIGN: Patients with VRE BSI (case-patients) were compared with VRE-colonized (control) patients from September 1994 through August 1997. Oral mucositis severity was recorded on the day of VRE BSI for case-patients and on hospital day 22 (median day of hospitalization of case-patient VRE BSI) for controls. There were 19 case-patients and 31 controls. RESULTS: In univariate analysis, case-patients were significantly more likely than controls to have a higher mucositis severity score, diarrhea, or a higher severity of illness score. In multivariate analysis, only mucositis remained as an independent risk factor, and increasing mucositis score was significantly associated with VRE BSI. CONCLUSIONS: Mucositis severity was independently associated with an increasing risk for VRE BSI. Interventions to alter mucositis severity may help to prevent VRE BSI in hospitalized cancer patients.
OBJECTIVE: To study vancomycin-resistant Enterococcus (VRE) prevalence, risk factors, and clustering among hospital inpatients. DESIGN: Rectal-swab prevalence culture survey conducted from February 5 to March 22, 1996. SETTING: The Veterans' Affairs Medical Center, Atlanta, Georgia. PATIENTS: Hospital (medical and surgical) inpatients. RESULTS: The overall VRE prevalence was 29% (42/147 patients). The VRE prevalence was 52% (38/73 patients) among patients who had received at least one of six specific antimicrobials during the preceding 120 days, compared with only 5% (4/74) among those who had not received the antimicrobials (relative risk, 9.6; P<.001). The longer the period (up to 120 days) during which antimicrobial use was studied, the more closely VRE status was predicted. Among 67 hospital patients in 28 multibed rooms, clustering of VRE among current roommates was not found. CONCLUSIONS: At this hospital with relatively high VRE prevalence, VRE colonization was related to antibiotic use but not to roommate VRE status. In hospitals with a similar VRE epidemiology, obtaining cultures from roommates of VRE-positive patients may not be as efficient a strategy for identifying VRE-colonized patients as obtaining screening cultures from patients who have received antimicrobials.
To examine the prevalence of and survival rates for coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), data were analyzed from all HIV-infected patients tested for HCV antibody from January 1992 until May 1997. The prevalence of HCV infection among 350 HIV-infected patients was 33%. By univariate analysis, HCV-positive (HCV+) patients were more likely to be older (P = .003), be positive for hepatitis B core antibody (P = .006), be black (P = .001), be intravenous drug users (P = .001), and have an abnormal level of aspartate aminotransferase (AST) (P = .001). In a logistic regression model, only intravenous drug abuse and abnormal AST level remained independently associated with HCV positivity. Length of survival, as determined by the Cox proportional hazards model, was similar for HCV+ vs. HCV- patients when analyzed for three different endpoints: time from diagnosis of HIV to diagnosis of AIDS, time from diagnosis of HIV to death, and time from diagnosis of AIDS to death. The prevalence of HCV infection in this population is high but does not appear to affect HIV progression or survival.
Monitoring for lamivudine (3TC) resistance is important both for the clinical management of human immunodeficiency virus type 1 (HIV-1)-infected patients treated with 3TC and for surveillance of transmission of 3TC-resistant HIV-1. We developed a novel non-culture-based assay for the rapid analysis of phenotypic resistance to 3TC of HIV-1 in plasma. The assay measures the susceptibility of HIV-1 reverse transcriptase (RT) activity to 3TC triphosphate (3TC-TP) in plasma. RT detection was done by the Amp-RT assay, an ultrasensitive PCR-based RT assay. Under our assay conditions, we found that 5 microM 3TC-TP inhibited RT activity from wild-type (WT), zidovudine-resistant, or nevirapine-resistant HIV-1 but not from HIV-1 carrying either the M184V mutation or multidrug (MD) resistance mutations (77L/116Y/151M or 62V/75I/77L/116Y/151M). Mixing experiments showed a detection threshold of 10% 3TC-resistant virus (M184V) in a background of WT HIV-1. To validate the assay for the detection of phenotypic resistance of HIV-1 to 3TC in plasma samples, HIV-1 RT in 30 plasma specimens collected from 15 patients before and during therapy with 3TC was tested for evidence of phenotypic resistance by the Amp-RT assay. The results were compared with those of genotypic analysis. The RT in 12 samples was found to be 3TC sensitive, while the RT in 18 samples had evidence of phenotypic resistance. All 12 samples with 3TC-sensitive RT had WT genotypes at codon 184 and were retrieved before treatment with 3TC. In contrast, all 18 specimens with 3TC-resistant RT were posttherapy samples. This assay provides a simple, rapid, and reliable method for the detection of phenotypic resistance of HIV-1 to 3TC in plasma.
Disseminated Mycobacterium avium complex (MAC) infection continues to be a common opportunistic infection in patients infected with human immunodeficiency virus (HIV). The optimal therapy for disseminated MAC infection is unclear. We compared azithromycin plus ethambutol with clarithromycin plus ethambutol in the treatment of disseminated MAC infection in HIV type 1-infected patients, examining the frequency of bacteremia clearance, time to clearance, and study drug tolerance after 16 weeks of therapy. Fifty-nine patients for whom blood cultures were positive for MAC were enrolled in the study from 10 university-affiliated Veterans Affairs Medical Centers. Thirty-seven patients were evaluable for determination of quantitative bacteremia and clinical outcomes. Clearance of bacteremia was seen at the final visit in 37.5% of azithromycin-treated patients and in 85.7% of clarithromycin-treated patients (P = .007). The estimated median time to clearance of bacteremia was also significantly different between the two treatment arms: 4.38 weeks for clarithromycin recipients vs. > 16 weeks for azithromycin recipients (P = .0018). Only one isolate developed macrolide resistance during therapy. Abatement of symptoms, other laboratory-evident abnormalities, and adverse effects were similar in the two groups. At the doses used in this study, clarithromycin/ethambutol produced a more rapid resolution of bacteremia than did azithromycin/ethambutol, and clarithromycin/ethambutol was more effective at sterilization of blood cultures after 16 weeks of therapy.
OBJECTIVE: To describe the characteristics of and trends in nosocomial infection among human immunodeficiency virus (HIV)-infected patients. DESIGN: Multicenter prospective cohort study. SETTING/PATIENTS: HIV-infected patients were enrolled at time of first inpatient admission at five Veterans' Administration Medical Centers (VAMCs). RESULTS: As of March 1995, 2,541 patients with 6,625 inpatient admissions had been monitored in the five VAMCs. A total of 530 nosocomial infections were detected using standard Centers for Disease Control and Prevention definitions. Overall distribution by infection site was 31% for primary bloodstream infections (BSIs), 28% for urinary tract infections, 15% for pneumonia, and 26% for all other sites. Of BSIs, 63% were central line-associated bloodstream infections (CLABs). The rate of CLABs per 1,000 central line days was 6.5 (range, 2.3-8.3) for all patients from participating hospitals, similar to the median CLAB rate of 6.0 for patients in medical intensive-care units (ICUs) of National Nosocomial Infections Surveillance (NNIS) System hospitals from January 1990 through September 1994. For ICU-specific CLABs, the rate from hospitals reporting at least one ICU CLAB was 12.7 (range, 12.1-13.1), comparable to the 90th percentile of NNIS hospital medical ICUs (13.1). Staphylococcus aureus, associated with 35% of BSIs, was the most common nosocomial BSI pathogen. Our data demonstrated the following: 13 (10%) of 134 patients with CD4 counts > or = 200 cells/mm3 had a CLAB, compared with 61 (6%) of 1,011 patients with CD4 counts < 200 cells/mm3, P = .08; the per-day risk of CLABs did not change with increased duration of catheterization (P = .4); and the per-day risk of a temporary (ie, short-term) CLAB was greater than that of a permanent CLAB (P < .001). CONCLUSIONS: The data suggest that HIV-infected patients were at higher risk of acquiring a BSI than were patients in the NNIS population; patients with CD4 counts > or = 200 cell/mm3 and temporary central lines were at increased risk for BSI, perhaps reflecting widespread prophylaxis with trimethoprim-sulfamethoxazole among patients with CD4 counts < 200 cells/mm3, and, in contrast to most studies, S aureus, not coagulase-negative Staphylococcus, was the most common BSI pathogen.
A newly described species of mycobacteria, Mycobacterium celatum, has rarely been reported as a cause of localized and disseminated human disease and can easily be misidentified as Mycobacterium xenopi when identification is based on biochemical testing alone. We report two cases of pneumonia and bacteremia due to M. celatum in patients with AIDS. In one case, diagnosis and initiation of therapy were delayed by misidentification of the infecting organism as M. xenopi. Genomic analysis or high-performance liquid chromatography is necessary to distinguish the two species. The finding in our two cases and a review of existing literature indicate that pulmonary disease may be an important manifestation of infection with M. celatum, especially in patients with AIDS. Further studies are needed to determine the incidence and clinical relevance of this organism in patients with AIDS and the optimal treatment regimens.
Upon prolonged treatment with various antiretroviral nucleoside analogs such as 3'-azido-3'-deoxythymidine, 2',3'-dideoxyinosine, 2',3'-dideoxycytidine, (-)- beta-L-2', 3'dideoxy-3'thiacytidine and 2',3'-didehydro-3'-deoxythymidine, selection of human immunodeficiency virus type 1 (HIV-1) strains with mutations in the reverse transcriptase (RT) gene has been reported. We designed a reverse hybridization line probe assay (LiPA) for the rapid and simultaneous characterization of the following variations in the RT gene: M41 or L41; T69, N69, A69, or D69; K70 or R70; L74 or V74; V75 or T75; M184, I184, or V184; T215, Y215, or F215; and K219, Q219, or E219. Nucleotide polymorphisms for codon L41 (TTG or CTG), T69 (ACT or ACA), V75 (GTA or GTG), T215 (ACC or ACT), and Y215 (TAC or TAT) could be detected. In addition to the codons mentioned above, several third-letter polymorphisms in the direct vicinity of the target codons (E40, E42, K43, K73, D76, Q182, Y183, D185, G213, F214, and L214) were found, and specific probes were selected. In total, 48 probes were designed and applied to the LiPA test strips and optimized with a well-characterized and representative reference panel. Plasma samples from 358 HIV-infected patients were analyzed with all 48 probes. The amino acid profiles could be deduced by LiPA hybridization in an average of 92.7% of the samples for each individual codon. When combined with changes in viral load and CD4+ T-cell count, this LiPA approach proved to be useful in studying genetic resistance in follow-up samples from antiretroviral agent-treated HIV-1-infected individuals.
Surveillance cultures for vancomycin-resistant enterococci (VRE) are time-consuming and expensive for the laboratory to perform. Therefore, we investigated the use of PCR as an alternative method of detecting and identifying VRE directly in fecal samples. PCR primers directed to vanA, vanB, vanC1, vanC2, and enterococcal ligase genes were used to detect and identify VRE in fecal material obtained by rectal or perirectal swabbing. Although PCR-inhibitory substances were present in DNA prepared directly from the swabs, the inhibitory substances could be reduced by processing the nucleic acid with two commercially available DNA preparation columns. Fecal material from 333 swabs was cultured on several selective agar media before and after broth enrichment. DNA was extracted from the fecal material and was analyzed by PCR. By using all four primer sets, only 59 (67.8%) of the samples were positive for vanA. However, after retesting the negative samples with only the vanA primer set, 77 (88.5%) of 87 specimens that were culture positive for Enterococcus faecium containing vanA were positive by PCR. One specimen was PCR positive for the vanA gene but culture negative for enterococci. The specificity of the vanA assay was 99.6%. PCR analysis of enrichment broth samples with all four primers sets after 15 to 18 h of incubation detected 74 (85.1%) of the 87 culture-positive specimens. The specificity of the vanA assay after the enrichment step was 100%. No vanB-containing enterococci were recovered by culture. Since 16 samples can be tested by PCR in 4 h (including electrophoresis), identification of VRE is possible within 8 h of specimen submission at a cost of approximately $10.12/assay. Thus, PCR may be a cost-effective alternative to culture for surveillance of VRE in some hospitals.
Meningitis is a frequent complication of the human immunodeficiency infection. Possible causes include bacterial, fungal, mycobacterial, syphilitic, and vital pathogens (including the human immunodeficiency virus). Drugs must also be considered in the differential diagnosis. Two patients with probable trimethoprim-sulfamethoxazole-induced meningitis are described in the setting of human immunodeficiency virus infection.
OBJECTIVE: To evaluate the effect of the type of Pneumocystis carinii pneumonia (PCP) prophylaxis on the development of community-acquired bacteremia. DESIGN: Case-control study using all cases of community-acquired bacteremia identified prospectively during a longitudinal study of all infections in a cohort of HIV-infected persons. SETTING: University-affiliated Department of Veterans Affairs Medical Center HIV program. PATIENTS: All patients with community-acquired bacteremia seen at the facility between January 1990 and December 1995 were included. Controls, seen at the same facility and matched by date and CD4 count, were used to assess risk factors. A total of 57 cases and 114 controls were analysed. MAIN OUTCOME MEASURES: Risk of development of bacteremia, distribution of organisms, and effect of specific prophylactic regimens for PCP. RESULTS: Bacteremia was caused by Staphylococcus aureus (23%), Pseudomonas aeruginosa (18%), Escherichia coli (16%), Streptococcus pneumoniae (14%) and others (31%). Groups were similar by age, race, HIV risk factors and CD4 count. The presence of an intravenous catheter was mildly predictive of the development of bacteremia [odds ratio (OR), 2.67; P = 0.024]. Type of PCP prophylaxis in cases and controls with CD4 < 200 x 10(6)/l included co-trimoxazole (trimethoprim-sulfamethoxazole, TMP-SMX; 31 and 60%, respectively), dapsone (33 and 24%, respectively) and aerosolized pentamidine (27 and 13%, respectively). Use of TMP-SMX (but not dapsone or aerosolized pentamidine) was associated with the absence of bacteremia (OR, 0.28; P = 0.001). A similar protective effect was found when controlling for the presence of an intravenous catheter. CONCLUSION: PCP prophylaxis with TMP-SMX apparently protects against community-acquired bacteremia in HIV-infected persons.
To improve understanding of the epidemiology of cryptococcal disease, we analyzed the multilocus genotype distribution of 358 Cryptococcus neoformans isolates obtained from 251 patients through active surveillance in four U.S. geographic areas from 1992 through 1994. Isolates of the predominant enzyme electrophoretic type (ET), ET-1, were recovered in significantly greater proportion from Atlanta, Ga., Houston, Tex., and all major metropolitan areas of Alabama than from San Francisco, Calif. ET-2 and ET-7 complex (serotype AD) isolates were recovered predominantly from San Francisco. ET-3 was recovered less frequently from San Francisco than from the three other locations. These findings may reflect geographic differences in exposure to environmental strains or the identification of previously unrecognized C. neoformans clusters. Analysis by random amplified polymorphic DNA-PCR subtyping further divided 67 ET-1 isolates into 19 additional subtypes, none of which could be associated with a particular geographic region. Multiple isolates from the same patient always revealed the same multilocus enzyme electrophoresis and random amplified polymorphic DNA subtypes. No differences in subtype distribution were found when isolates from AIDS patients were compared with those from persons without or with another underlying disease, although one C. noeformans var. gattii isolate was obtained from an AIDS patient. When body site distribution was analyzed, ET-4 was disproportionately recovered from skin or surface body sites. Evidence for linkage disequilibrium in this fungal population suggests that virulent C. neoformans possesses a clonal population structure. Continued application of molecular subtyping methods will be useful in tracking the source, transmission, and relative virulence of different C. neoformans strains.
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Pyrimethamine, 25 mg thrice weekly, was evaluated as primary prophylaxis for toxoplasmic encephalitis (TE) in a double-blind, randomized clinical trial in patients with human immunodeficiency virus (HIV) disease, absolute CD4 lymphocyte count of < 200/microL (or prior AIDS-defining opportunistic infection), and the presence of serum IgG to Toxoplasma gondii. Leucovorin was coadministered only for hematologic toxicity. There was a significantly higher death rate among patients receiving pyrimethamine (relative risk [RR], 2.5; 95% confidence interval [CI], 1.3-4.8; P = .006), even after adjusting for factors predictive of survival. The TE event rate was low in both treatment groups (not significant). Only 1 of 218 patients taking trimethoprim-sulfamethoxazole but 7 of 117 taking aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia developed TE (adjusted RR for the trimethoprim-sulfamethoxazole group, 0.16; 95% CI, 0.01-1.79; P = .14). Thus, for HIV-infected patients receiving trimethoprim-sulfamethoxazole, additional prophylaxis for TE appears unnecessary.
Recognizing the unique needs and demands of HIV-infected patients, it was decided to implement pharmaceutical care in a VAMC outpatient HIV clinic. Services provided to the patients by the pharmacist include drug information, medication counseling with the help of educational handouts, and drug-related problem identification and resolution. The pharmacist also serves as a liaison between the patient and the VAMC outpatient pharmacy if conflicts arise. Services provided to the other members of the HIV clinic team include the provision of drug information and participation in clinical research. In addition, the HIV clinic provides a training site for pharmacy practice residents and Doctor of Pharmacy students on their ambulatory care rotation.