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R D Arbeit

Publications and source records attributed to R D Arbeit.

At least 37 records · Page 2Linked to original sources

How to select and interpret molecular strain typing methods for epidemiological studies of bacterial infections: a review for healthcare epidemiologists. Molecular Typing Working Group of the Society for Healthcare Epidemiology of America.

Strain typing is an integral part of epidemiological investigations of nosocomial infections. Methods for distinguishing among bacterial strains have improved dramatically over the last 5 years, due mainly to the introduction of molecular technology. Although not all molecular techniques are equally effective for typing all organisms, pulsed-field gel electrophoresis is the technique currently favored for most nosocomial pathogens. Criteria to aid epidemiologists in interpreting results have been published. Nucleic acid amplification-based typing methods also are applicable to many organisms and can be completed within a single day, but interpretive criteria still are under debate. Strain typing cannot be used to replace a sound epidemiological investigation, but serves as a useful adjunct to such investigations.

Bacterial Typing Techniques↗

Immunization of healthy adult subjects in the United States with inactivated Mycobacterium vaccae administered in a three-dose series.

Heat-killed Mycobacterium vaccae vaccine was administered in a three-dose intradermal schedule to 10 healthy adult volunteers at 0, 2, and 10 months. Local and systemic side effects were monitored and vaccine site reactions were measured and photographed at visits 2 days, 14 days, and 2 months after each dose. Reactions to skin tests with purified protein derivative (PPD) and Mycobacterium avium sensitin (MAS) and titers of antibody to arabinose lipoarabinomannin were determined at baseline and after each dose of vaccine. Lymphocyte proliferation responses to MAS were determined after the final dose of vaccine. Immunization was safe and well tolerated, with maximal induration (range, 6-25 mm) at 2 days. PPD skin test conversions did not occur. Seven subjects completed the three-dose schedule; preexisting immunologic responses to mycobacteria were boosted in three, and a new response was elicited in one. M. vaccae vaccine is safe and induces measurable immunologic responses to mycobacterial antigens in some healthy adults.

Adult↗

Immunization of HIV-infected adults with a three-dose series of inactivated Mycobacterium vaccae.

Heat-killed Mycobacterium vaccae vaccine was administered in a 3-dose schedule to 12 HIV-infected adults with CD4 cell counts > or = 300/mm3. Local and systemic side effects were monitored. Delayed-type hypersensitivity to purified protein derivative and Mycobacterium avium sensitin was measured at baseline and after the final dose. Antibody to aralipoarabinomannin, man-lipoarabinomannin, and a short-term culture filtrate of Mycobacterium tuberculosis were also measured. Lymphocyte proliferation responses to M avium sensitin and M vaccae sonicate were determined. Vaccine site induration was maximal at 2 days (median, 6 mm) and no systemic side effects were noted. Purified protein derivative skin test conversions did not occur. Changes in CD4 counts and HIV viral load were not significant. Three (27%) of 11 subjects who completed the trial showed either M avium skin test (n = 1) or short-term culture filtrate antibody (n = 2) responses. A three-dose schedule of M vaccae vaccine is safe and well tolerated in adults with early HIV infection and produces detectable immunologic responses in a subset of these subjects.

AIDS-Related Opportunistic Infections↗

The risks and benefits of childhood bacille Calmette-Guérin immunization among adults with AIDS. International MAC study groups.

OBJECTIVE: To define the risks of disseminated bacille Calmette-Guérin (BCG) or disseminated Mycobacterium tuberculosis in adults with AIDS who were immunized with BCG in childhood. DESIGN: HIV-infected patients with CD4 < 200 x 10(6)/l were enrolled from five study sites (New Hampshire, Boston, Finland, Trinidad and Kenya). Prior BCG immunization was determined and blood cultures for mycobacteria were obtained at study entry and at 6 months. Acid-fast bacilli were identified as Mycobacterium tuberculosis complex (MTBC) using DNA probes. MTBC isolates were then typed by both IS6110 restriction fragment length polymorphism and polymerase chain reaction/restriction enzyme analysis. SETTING: Most patients in New Hampshire and Finland were outpatients; most patients in Trinidad were inpatients with terminal illness; and most patients in Kenya were outpatients, although 44 were inpatients with terminal illness. PARTICIPANTS: A total of 566 patients were enrolled, including 155 with childhood BCG immunization; 318 patients had a single study visit and culture, and 248 patients had two study visits and cultures. MAIN OUTCOME MEASURES: Isolation and identification of mycobacteria from blood cultures. RESULTS: Blood cultures were positive for MTBC in 21 patients; none were positive for M. bovis BCG, and 21 were M. tuberculosis-positive. In Trinidad, seven (87%) out of eight isolates of M. tuberculosis were indistinguishable by IS6110 typing; BCG immunization was associated with a decreased risk of bacteremic infection with M. tuberculosis (P = 0.05). CONCLUSIONS: The risk of disseminated BCG among adult AIDS patients with childhood BCG immunization is very low. Childhood BCG immunization is associated with protection against bacteremia with M. tuberculosis among adults with advanced AIDS in Trinidad.

AIDS-Related Opportunistic Infections↗

Clinical and molecular epidemiology of sporadic and clustered cases of nosocomial Clostridium difficile diarrhea.

PURPOSE: A prospective clinical and molecular epidemiologic study was conducted to define the frequency of nosocomial Clostridium difficile patient-to-patient transmission in an urban tertiary referral hospital. PATIENTS AND METHODS: Over a 6-month period, environmental cultures for C difficile were obtained from patients with new positive stool cytotoxin assay (index cases); stool samples were obtained from selected patient contacts (the roommate, occupants of adjacent rooms, and the patient occupying the index room after discharge of the index case); and hand cultures were obtained from personnel contacts. C difficile isolates were analyzed by pulse-field gel electrophoresis (PFGE) or, for isolates that were nontypeable by PFGE, by restriction enzyme analysis. RESULTS: During the study period, we identified 98 index cases of C difficile toxin-associated diarrhea, including focal outbreaks on two wards totaling 26 cases within a 2-month interval. Environmental contamination was detected at > or = 1 sites in 58% of rooms and often involved wide dispersed areas. Among 99 prospectively identified patient contacts, C difficile was cultured from the stool of 31 (31%), including 12 with diarrhea and 19 who were asymptomatic. C difficile was cultured from the hands of 10 (14%) of 73 personnel. Molecular analysis resolved 31 typing profiles among the index isolates; the most common profile (designated strain D1) was represented by 30 isolates. Among the isolates from patient contacts, 5 of 12 from symptomatic contacts matched the corresponding index isolate, and only 1 of 19 from asymptomatically colonized contacts matched. Transmission to personnel or patient contacts of the strain cultured from the corresponding index case was correlated strongly with the intensity of environmental contamination. Strain D1 was frequently represented among isolates associated with heavy environmental contamination, with personnel carriage, and with development of symptomatic illness among prospectively identified contacts. CONCLUSIONS: Intense environmental contamination and transmission to close personnel and patient contacts represented coordinated properties of an individual epidemic strain. For most epidemiologically linked contacts, positive cultures for C difficile did not result from transmission from the presumed index case.

Bacterial Toxins↗

The international epidemiology of disseminated Mycobacterium avium complex infection in AIDS. International MAC Study Group.

OBJECTIVE: To determine rates of disseminated Mycobacterium avium complex (MAC) infection among AIDS patients in developed and developing countries, and to determine whether different rates reflect differences in exposure or immunity, or both. DESIGN: Prospective cohort study. SETTING: University hospitals and outpatient AIDS programs. METHODS: HIV-infected subjects with CD4 counts < 200 x 10(6)/l were interviewed and had CD4 lymphocyte counts, blood cultures for mycobacteria (baseline and at 6 months), and skin tests with purified protein derivative (PPD) and M. avium sensitin. RESULTS: Among 566 study patients rates of disseminated MAC were 10.5-21.6% in New Hampshire, Boston and Finland compared to 2.4-2.6% in Trinidad and Kenya (P < 0.001). PPD skin test reactions > or = 5 mm were present in 20% of patients from Kenya compared to 1% at other sites (P < 0.001). Among patients from the United States and Finland, multiple logistic regression indicated that occupational exposure to soil and water was associated with a decreased risk of disseminated MAC, whereas the following were associated with an increased risk of disseminated MAC: low CD4 count, swimming in an indoor pool, history of bronchoscopy, regular consumption of raw or partially cooked fish/shellfish and treatment with granulocyte colony-stimulating factor. CONCLUSIONS: Rates of disseminated MAC in AIDS are higher in developed than developing countries and are due to both differences in exposure and differences in immunity. These data provide a rationale for prevention of MAC through both active immunization and reduction in exposure to the organism.

AIDS-Related Opportunistic Infections↗

Use of cleaved amplified polymorphic sequences to distinguish strains of Staphylococcus epidermidis.

We examined the utility of a PCR-based method termed cleaved amplified polymorphic sequences (CAPS) to type 35 well-characterized isolates of Staphylococcus epidermidis. The results were compared with detailed epidemiologic information and typing obtained by using pulsed-field gel electrophoresis (PFGE). To identify CAPS markers for this study, eight pairs of oligonucleotide primers corresponding to five previously sequenced S. epidermidis genes were synthesized and then used to amplify DNA sequences from the S. epidermidis strains by using PCR. Amplified products were reproducibly obtained for seven of eight primer pairs from chromosomal DNA of 33 of the 35 isolates. Seven restriction site polymorphisms were found in five of the amplified products when they were subjected to digestion with a panel of restriction endonucleases. Each fragment-enzyme combination that was polymorphic demonstrated only two alleles in the 33 S. epidermidis isolates analyzed, corresponding to the presence or absence of a single restriction site. Overall, five distinct combinations of alleles were detected and were designated CAPS types A through E. There was a close correlation between the CAPS grouping, the epidemiologic information for the strains, and grouping by PFGE following SmaI digestion of chromosomal DNA. Although PFGE analysis was more discriminatory than typing based on the limited number of CAPS markers used in this study (isolates from the same CAPS group were sometimes distributed into more than one PFGE group), no isolates from the same PFGE group were found in more than one CAPS group. The CAPS procedure was highly reproducible, in contrast to published experience with arbitrarily primed PCR. These preliminary data suggest that CAPS represents a PCR-based technique for strain typing that is highly reproducible, rapid, utilizes widely available technologies, and provides results that are relatively easy to interpret and express.

Bacterial Typing Techniques↗

Disseminated Mycobacterium avium infection among HIV-infected patients in Kenya.

Previous studies from Africa have been unable to identify disseminated Mycobacterium avium complex (MAC) infection in patients with advanced human immunodeficiency virus (HIV) infection. We performed mycobacterial blood cultures and CD4 counts on 48 symptomatic adults with advanced HIV infection admitted to the hospital in Nairobi, Kenya over 4 weeks in 1992. Fourteen patients had mycobacteremia; these patients had significantly lower CD4 counts than the patients with negative cultures (14/mm3 vs. 85/mm3; p < 0.01). Three patients (6%) were bacteremic with M. avium (mean CD4 count, 10/mm3) and 11 (23%) were bacteremic with Mycobacterium tuberculosis complex (MTB) (mean CD4 count, 15/mm3). Thus, M. avium bacteremia was detected significantly less frequently in the study population than MTB bacteremia (p = 0.04). The minimum rate for HIV-associated disseminated M. avium infection in patients admitted to the hospital in Nairobi was estimated to be approximately 1%. Patients with mycobacteremia died or were discharged home sick before the diagnosis was made. Disseminated M. avium does occur in adults with advanced HIV infection in sub-Saharan Africa, but is less common than disseminated MTB.

Acquired Immunodeficiency Syndrome↗

Variation and persistence of methicillin-resistant Staphylococcus aureus strains among individual patients over extended periods of time.

To determine the strain variation and persistence among isolates of methicillin-resistant Staphylococcus aureus (MRSA) cultured from patients with colonization over extended time spans, pulsed-field gel electrophoresis was used to analyze the isolates from 47 patients for whom at least two mecA-positive isolates collected a minimum of six months apart were available. For 22 (47%) patients, the isolates represented multiple distinct strains of Staphylococcus aureus, while 20 (43%) patients had only a single strain detected; five (11%) patients had similar, genetically related isolates. MRSA were frequently associated with mucocutaneous abnormalities; 29 (62%) patients had focal cutaneous defects, and ten (21%) had chronic dermatitis. Multiple strains of MRSA were detected more frequently than single strains among patients in whom the initial focus of MRSA resolved clinically and another mucocutaneous defect subsequently developed compared to patients with clinically persistent foci (11/15 versus 9/23, respectively; p = 0.05, Fisher's exact test). Among the 21 patients in this series for whom isolates cultured within a two-month time span were available, there were seven (33%) patients with multiple strains of MRSA, including one patient with polyclonal bacteremia. In summary, patients with long-term MRSA colonization often have several different strains of MRSA, which typically change overtime in association with removal or resolution of a colonized focus and the recurrence of mucocutaneous defects.

Anti-Bacterial Agents↗

A pseudoepidemic due to laboratory contamination deciphered by molecular analysis.

OBJECTIVE: A clinical, microbiological, and molecular analysis to identify the source of a cluster of pseudoinfections. DESIGNS: Retrospective analysis of the cases, prospective epidemiologic survey, and laboratory investigation. Molecular analysis of the isolates was performed using pulsed-field gel electrophoresis (PFGE). SETTING: A tertiary Veterans Affairs medical center. PATIENTS: Three patients admitted over a 2-week period with musculoskeletal complaints had one or more joint fluid specimens submitted for culture. In each case, anaerobic chopped meat-glucose broth (CMGB) tubes yielded one or more organisms not typically associated with septic arthritis (Enterobacter cloacae, Enterococcus faecium, Enterococcus casseliflavus, Enterococcus faecalis, Escherichia hermannii, and Pseudomonas diminuti). The first three organisms were isolated from specimens from multiple patients. Two patients had multiple positive cultures; for two patients, separate cultures yielded additional organisms on solid media. RESULTS: Laboratory investigation yielded an isolate of E faecium from 1 of 30 sham-inoculated CMGB tubes. PFGE analysis demonstrated that a single strain of E cloacae was isolated from four CMGB tubes representing all three patients, and a single strain of E faecium was isolated from CMGB tubes representing two patients and the sham-inoculated tube. CONCLUSIONS: The application of molecular typing clearly demonstrated clonality among the isolates and indicated that a common source of contamination, most likely the CMGB tubes, was responsible for these cases.

Adult↗

Persistent and relapsing infections associated with small-colony variants of Staphylococcus aureus.

Small-colony variants (SCVs) of Staphylococcus aureus were cultured from five patients with persistent and relapsing infections. All five SCV strains were nonhemolytic and nonpigmented and grew very slowly on routine culture media in an ambient atmosphere. In several instances, these phenotypic characteristics led to the initial misidentification of the organisms in the clinical microbiology laboratory. All four strains available for further analysis were shown to be auxotrophs that reverted to normal growth and morphology in the presence of menadione, hemin, and/or a CO2 supplement. Similarly, these isolates were resistant to aminoglycosides under routine conditions but susceptible in the presence of the metabolic supplements. For two patients, the large and small colony forms isolated concurrently were indistinguishable when analyzed by pulsed field gel electrophoresis and thus represented phenotypic variants within individual clones. We propose a model relating the phenotypic characteristics of S. aureus SCVs with the clinical pattern of persistent and relapsing infection.

Aged↗

Clonal relationships among bloodstream isolates of Escherichia coli.

The clonal relationships among 187 bloodstream isolates of Escherichia coli from 179 patients at Boston, Mass., Long Beach, Calif., and Nairobi, Kenya, were determined by multilocus enzyme electrophoresis (MLEE), analysis of polymorphisms associated with the ribosomal operon (ribotyping), and serotyping. MLEE based on 20 enzymes resolved 101 electrophoretic types (ETs), forming five clusters; ribotyping resolved 56 distinct patterns concordant with the analysis by MLEE. The isolates at each study site formed a genetically diverse group and demonstrated similar clonal structures, with the same small subset of lineages accounting for the majority of isolates at each site. Moreover, two ribotypes accounted for approximately 30% of the isolates at each study site. One cluster contained the majority (65%) of isolates and, by direct comparison of the ETs and ribotypes of individual isolates, was genetically indistinguishable from the largest cluster for each of two other collections of E. coli causing pyelonephritis and neonatal meningitis (R. K. Selander, T. K. Korhonen, V. Väisänen-Rhen, P. H. Williams, P. E. Pattison, and D. A. Caugent, Infect. Immun. 52:213-222, 1986; M. Arthur, C. E. Johnson, R. H. Rubin, R. D. Arbeit, C. Campanelli, C. Kim, S. Steinbach, M. Agarwal, R. Wilkinson, and R. Goldstein, Infect. Immun. 57:303-313, 1989), thus defining a virulent set of lineages. The isolates within these virulent lineages typically carried DNA homologous to the adhesin operon pap or sfa and the hemolysin operon hly and expressed O1, O2, O4, O6, O18, O25, or O75 antigens. DNA homologous to pap was distributed among isolates of each major cluster, whereas hly was restricted to isolates of two clusters, typically detected in pap-positive strains, and sfa was restricted to isolates of one cluster, typically detected in pap- and hly-positive strains. The occurrence of pap-positive isolates in the same geographically and genetically divergent lineages suggests that this operon was acquired early in the radiation of E. coli, while hly and sfa were acquired subsequently, most likely by pap-positive and pap- and hly-positive precursors, respectively.

Adhesins, Escherichia coli↗

Polyclonal Mycobacterium avium infections in patients with AIDS: variations in antimicrobial susceptibilities of different strains of M. avium isolated from the same patient.

Broth microdilution MICs were determined for pairs of strains isolated from five AIDS patients with polyclonal Mycobacterium avium infection. Four (80%) of the five patients were infected simultaneously with strains having different antimicrobial susceptibility patterns. These findings have implications for the interpretation of susceptibility data in M. avium prophylaxis and treatment trials.

AIDS-Related Opportunistic Infections↗

Persistent colonisation of potable water as a source of Mycobacterium avium infection in AIDS.

The source of Mycobacterium avium infection in AIDS has not been identified and it is not known whether most patients with AIDS acquire the organism from recent infection or by reactivation of previous infection. As part of a prospective epidemiological study, we isolated multiple colonies of M avium from patients with AIDS and from potable water to which they had been exposed. All isolates were analysed with pulsed field gel electrophoresis (PFGE). As judged by PFGE, 29 (81%) of 36 patients were infected with one or more unique clinical strains of M avium. 7 patients (19%) were infected with three groups of common strains. Group 1 included 3 patients who lived in separate rural areas and had no common exposures apart from treatment at hospital A. The same strain was isolated repeatedly during 41 months from a recirculating hot water system at hospital A; residential water cultures were negative. Group 2 included 2 patients with no common exposures apart from treatment at hospital B; the same strain was isolated repeatedly over a period of 24 months from a recirculating hot water system at hospital B. Patients in groups 1 and 2 had numerous possible exposures to hospital hot water. Group 3 included 2 patients treated at the same methadone treatment facility. In an institution the hot water system may be persistently colonised with a particular strain of M avium. HIV-infected patients exposed to these water sources can develop disseminated M avium infection.

AIDS-Related Opportunistic Infections↗