Randomized, open-label trial of azithromycin plus ethambutol vs. clarithromycin plus ethambutol as therapy for Mycobacterium avium complex bacteremia in patients with human immunodeficiency virus infection. Veterans Affairs HIV Research Consortium.

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.

Comparison of three methods for recovery of yeasts from hands of health-care workers.

This study compared three methods for the detection of yeasts on the hands of 30 nurses: (i) direct finger impressions on inhibitory mold agar plates, (ii) bag washes in brain heart infusion broth, and (iii) bag washes in brain heart infusion broth supplemented with gentamicin and vancomycin. The antimicrobial agent-supplemented bag wash method identified the greatest number of yeast carriers and yielded the most yeast isolates, especially non-C. albicans Candida spp.

High frequency of yeast carriage on hands of hospital personnel.

The hands of 36 nurses and 21 nonnursing hospital employees were tested by culture with a modification of the broth wash technique. Seventy-five percent of the nurses and 81% of the nonnurses were found to harbor yeasts on their hands; 58% of nurses and 38% of nonnurses were carrying Candida spp.

Trimethoprim-sulfamethoxazole prophylaxis in granulocytopenic patients with acute leukemia: evaluation of serum antibiotic levels in a randomized, double-blind, placebo-controlled Department of Veterans Affairs Cooperative Study.

Despite widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis in neutropenic patients, questions remain regarding its efficacy, toxicity, the risk of selection of resistant isolates, and the relation of its activity to selective decolonization vs. the attainment of direct inhibitory levels within blood and tissues. We evaluated the effect of TMP-SMZ (160/800 mg orally every 12 hours) in 42 adult granulocytopenic patients (< 100 absolute neutrophils/mm3, mean duration 13.3 days) undergoing chemotherapy for acute leukemia at 11 participating Veterans Administration Medical Centers in a randomized, double-blind, placebo-controlled trial. No significant differences in survival, frequency of bacteremia, overall infections, use of systemic antimicrobial therapy, or adverse effects, including myelosuppression, were observed between patients receiving TMP-SMZ vs. those receiving placebo. All patients acquired trimethoprim-resistant organisms. Concentrations of trimethoprim in serum were significantly lower before febrile episodes than when patients were afebrile. These results suggest that the purported activity of TMP-SMZ may be related to the serum concentration achieved. Moreover, the results highlight the need for additional study of the value of antibiotic prophylaxis in neutropenic patients.

Sensitivity of surveillance cultures for the detection of methicillin-resistant Staphylococcus aureus in a nursing-home-care unit.

This study compared the sensitivity of nasal culture alone versus multiple-site cultures and single versus duplicate sampling for the detection of methicillin-resistant Staphylococcus aureus (MRSA)-colonized individuals in a nursing-home population. Repeat culture of 68 specimens collected from 35 colonized subjects yielded identical results for 57 specimens, (84%), and 89% of the colonized residents (31 of 35) were identified by the first culture of multiple sites. A single nares culture detected 27 (77%) of 35 (first screen) and 29 (83%) of 35 (second screen) residents colonized with MRSA at any site. The most cost-effective screening would consist of a nasal culture only or combined with a gastrostomy tube site, if applicable. To identify all colonized individuals, however, it would be necessary to culture more than one specimen from multiple sites on each resident.

Infected urachal remnants in the adult: case report and review.

Abnormalities of the urachus in adults are uncommon. Urachal tract remnants that abnormally remain patent are subject to infection. Urachal infection is frequently confused with a wide spectrum of midline intraabdominal or pelvic inflammatory disorders. Because the literature on urachal infection is primarily limited to articles in urology and surgical specialty journals, many physicians may not be familiar with the varied clinical manifestations. We describe a case of infection of a patent urachus in an adult and review the embryology and anatomy of the urachus as it relates to clinical presentation, evaluation, and management. Infection of a urachal remnant should be included in the broad differential diagnosis of omphalitis and midline abdominal or pelvic infections. Rarely, it may be a cause of recurrent urinary tract infection. Definitive management consists of surgical excision after the institution of antimicrobial therapy.

Comparison of in vitro adherence of methicillin-sensitive and methicillin-resistant Staphylococcus aureus to human nasal epithelial cells.

Reported nasal carriage rates of personnel caring for patients with methicillin-resistant Staphylococcus aureus (MRSA) range from 1% to 6% in contrast to nasal carriage rates of 45%-65% for methicillin-sensitive S. aureus (MSSA) in health care personnel under nonepidemic conditions. One proposed explanation for these conflicting observations was examined, namely that MSSA and MRSA differ in their ability to adhere to nasal epithelial cells. The adherence of 6 genotypically distinct strains of MSSA and MRSA to nasal epithelial cells from 5 healthy donors was compared using a radioisotope assay system (coefficient of variation, 26%). The effect of pretreating epithelial cells with S. aureus-derived ribitol teichoic acid, a known adhesin of S. aureus for epithelial cells, was also examined. The mean (+/- SE) adherence of MRSA compared with MSSA in 108 assays was 125 +/- 11.9 versus 129 +/- 8.3 viable bacteria per cell (P = .67). Dose-dependent competitive inhibition by ribitol teichoic acid was linear and equivalent for MRSA and MSSA (r, .949, P less than .001). As these in vitro results correlate to adherence in vivo, it would be anticipated that MRSA and MSSA would have an equal likelihood of nasal carriage. A critical review of published epidemiologic studies comparing MRSA and MSSA carriage rates also supports this hypothesis.

Antimicrobial therapy for methicillin-resistant Staphylococcus aureus colonization in residents and staff of a Veterans Affairs nursing home care unit.

OBJECTIVE: To evaluate the effect of antimicrobial therapy on patients and staff colonized with methicillin-resistant Staphylococcus aureus (MRSA) in a skilled nursing facility and to assess the role of the environment as a potential reservoir for MRSA in the nursing home setting. DESIGN: As part of a comprehensive program to control an MRSA outbreak in a nursing home, patients and staff colonized with MRSA received 1 of 3 antimicrobial decolonization regimens depending upon the site and extent of colonization. Followup cultures were performed during therapy and on days 2, 7, 14, and 30 following the completion of therapy. Cultures of the patients' inanimate environment (pajamas, sheet, and floor) were obtained during and after therapy. Antimicrobial susceptibility tests were performed on 54 MRSA isolates obtained before and 44 MRSA isolates recovered after therapy. SETTING: A 120-bed Veterans Affairs nursing home care unit. PARTICIPANTS: Thirty-six patients and 7 staff nurses colonized with MRSA at 1 or more sites. INTERVENTION: Decolonization therapy with rifampin, trimethoprim-sulfamethoxazole, and clindamycin used alone or in various combinations for 5 or 10 days in conjunction with other infection control measures employed to combat the MRSA outbreak. RESULTS: Twenty (56%) of the 36 NHCU patients were either persistently colonized or became recolonized with MRSA during the 30-day followup period. Positive cultures on day 3 during therapy frequently identified patients who subsequently exhibited persistent or recurrent colonization. Before therapy, 92% of MRSA isolates were susceptible to rifampin, whereas only 43% of the isolates obtained after therapy were susceptible. Sixteen (80%) of 20 patients with persistent or recurrent colonization had rifampin-resistant strains of MRSA isolated after therapy. Twenty-three (18%) of 125 environmental cultures obtained during and after therapy from patients who exhibited persistent or recurrent colonization were positive for MRSA, in contrast to 9 (8%) of 107 from patients who were successfully decolonized. CONCLUSIONS: The decolonization component of the outbreak control program was judged to be ineffective and potentially hazardous because colonization persisted or recurred in more than half of the patients, and substantial antimicrobial resistance was noted in MRSA stains isolated after therapy. Resistance, especially to rifampin, and possibly re-acquisition of MRSA from other human or environmental sources were 2 factors that appeared to impede the decolonization effort.

Methicillin-resistant Staphylococcus aureus in extended-care facilities: experiences in a Veterans' Affairs nursing home and a review of the literature.

OBJECTIVES: To delineate the spread of methicillin-resistant Staphylococcus aureus (MRSA) in a nursing home care unit (NHCU), determine its consequences, and discuss this experience in the context of reports from other nursing homes. DESIGN: Observational and descriptive; routine and special surveillance for MRSA, including a facility-wide prevalence survey; characterization of MRSA isolates by disk diffusion and agar dilution susceptibility studies and restriction enzyme analysis of plasmid (REAP) DNA. SETTING AND PATIENTS: A 120-bed skilled nursing facility that is an integral part of the Veterans' Affairs Medical Center (VAMC), Portland, Oregon. The patients are predominantly elderly men with severe underlying diseases and functional impairments. RESULTS: An asymptomatic carrier brought MRSA into the NHCU in December 1987. During the next 15 months, 24 additional MRSA cases were detected. A prevalence survey conducted in March 1989 indicated that 39 (34%) of the 114 patients and 8 (7%) of the 117 employees were colonized or infected with MRSA. All strains were resistant to ciprofloxacin. REAP DNA indicated that 37 of 41 strains recovered in the March survey had identical patterns. Although 16 episodes of MRSA infection occurred in NHCU residents during 1988 through 1989, the outbreak had little effect on overall patterns of infectious morbidity and mortality in the facility. The outbreak, however, did result in an increased MRSA caseload at the medical center's acute-care division. CONCLUSIONS: During the last three years, MRSA colonization and infection have become common in the NHCU at the Portland VAMC; this experience parallels that reported by several nursing homes in other parts of the country.

Postoperative infection in urologic surgery.

Postoperative urologic infection can result in morbidity and mortality. The diagnosis and management of postoperative bacterial urinary tract infections are discussed. Rational choice of antimicrobial therapy is based on the frequency at which specific bacterial pathogens are isolated and the local antimicrobial susceptibility patterns of common isolates. However, antibiotic resistance within the hospital setting is becoming a widespread problem. The wide spectrum of the third-generation cephalosporins affords them antimicrobial activity against common pathogens, and they share the low toxicity of other beta-lactam antibiotics.

Altered motility and duration of bacterial overgrowth in experimental blind loop syndrome.

To better understand the pathogenesis of the increased motility previously described in the blind loop rat, we studied the relationship between duration of bacterial overgrowth and both myoelectric activity and bacterial flora in this model. Myoelectric studies and quantitative bacterial cultures were performed on self-filling and self-emptying (control) blind loop rats one, two, and three weeks postoperatively. All self-filling blind loop rats had greater random action potential activity and higher frequencies of migrating action potential complexes than controls (P less than 0.05). One-week self-filling blind loop rats had a higher frequency of migrating action potential complexes (P less than 0.05) and a higher ratio of counts of Escherichia coli to Bacteroides species (P less than 0.05) than the two- or three-week self-filling blind loop groups. Thus, qualitative changes in myoelectric activity occur during the development of bacterial overgrowth in the blind loop rat which may reflect evolving alterations in the bacterial flora.

Jejunal infection with Campylobacter.

A patient had common variable immunodeficiency, chronic malabsorption, and Campylobacter jejuni infection. Infection was diagnosed by jejunal aspiration. A follow-up jejunal aspirate was culture positive at the same time that a stool culture was negative. Infection resulted in worsening of chronic diarrhea, but it was not associated with clinical features of colitis or proctitis. The duration of infection was prolonged and initial antimicrobial therapy was ineffective. Single drug therapy with erythromycin ethylsuccinate and then chloramphenicol led to the emergence of resistant organisms. After five months of bacterial excretion, combination therapy with metronidazole and neomycin sulfate eliminated the organism. This case emphasizes that the clinical manifestations and response to therapy of C jejuni infection can be altered in immunodeficient patients.

Detection of aminoglycoside ototoxicity by high-frequency auditory evaluation: selected case studies.

A practical monitoring procedure utilizing frequencies higher than those tested by conventional audiometry for the detection of ototoxicity has the potential for preventing or minimizing irreversible communication deficits in patients receiving aminoglycoside antibiotic therapy. If ototoxicity produced by these drugs could be detected before it progresses to involve the frequencies essential for communication, it might be possible to lower the dose or to change to another antibiotic to prevent a permanently handicapping hearing impairment. From a total of 77 patients monitored by serial audiograms, three case studies illustrate the various types of auditory sensitivity changes observed with high-frequency audiometry. Ototoxicity was generally detected by high-frequency auditory testing before it could be detected by conventional audiometric procedures. These cases demonstrate the utility of monitoring audition at frequencies higher than those tested conventionally in patients receiving aminoglycoside antibiotics.

Combination amdinocillin and cefoxitin therapy of multiply-resistant Serratia marcescens urinary tract infections.

Amdinocillin has previously been shown to be synergistic with other beta-lactam antibiotics against many gram-negative bacteria. We evaluated the safety, efficacy, and microbiologic activity of combination amdinocillin and cefoxitin treatment in 17 patients with complicated urinary tract infections caused by multiply-resistant Serratia marcescens. Patients were treated with amdinocillin, 40 mg/kg per day, and cefoxitin, 100 mg/kg per day, for five to 14 days. In vitro synergistic activity was observed for 17 isolates using broth checkerboard testing and for nine isolates using combination disc diffusion testing. Of the 17 patients treated, 11 were bacteriologically cured, one failed to respond, and five patients had a relapse after initial improvement. Relapses followed short-duration therapy. Amdinocillin with cefoxitin was well tolerated. Combination amdinocillin and cefoxitin therapy was efficacious and safe in treating complicated urinary tract infections caused by multiply-resistant S. marcescens.

Role of Clostridium difficile and Campylobacter jejuni in relapses of inflammatory bowel disease.

Findings from recent studies on the role of Clostridium difficile and Campylobacter jejuni in exacerbations of inflammatory bowel disease are in conflict. We examined stool specimens from 32 patients who had inflammatory bowel disease in relapse for the presence of C difficile and C difficile cytotoxin. In the last 19 cases stool specimens were also cultured for C jejuni. C difficile was identified in one patient who was receiving antimicrobial therapy. In no patient was C difficile cytotoxin detected. All cultures for C jejuni were negative. Routine screening of stool specimens for C difficile cytotoxin and C jejuni was not clinically useful in our patients during exacerbation of their inflammatory bowel disease.

Possible foodborne transmission in a case of pseudomembranous colitis due to Clostridium difficile: influence of gastrointestinal secretions on Clostridium difficile infection.

A 78-yr-old woman with a history of hypochlorhydria was found to have pseudomembranous colitis due to Clostridium difficile. She had not received previous antimicrobial therapy. Her onset of disease followed ingestion of possibly contaminated canned salmon, suggesting possible oral transmission of disease. We assessed the possibility of ingested Clostridium difficile organisms or cytotoxin surviving passage through the upper gastrointestinal tract. Normal gastric juice, hypochlorhydric gastric juice, and duodenal secretions were obtained from volunteers and tested for their ability to kill Clostridium difficile organisms or inactivate toxin. These in vitro studies indicated that the primary upper gastrointestinal barriers for ingested Clostridium difficile and cytotoxin were pH-dependent. We suggest that oral transmission of disease due to Clostridium difficile may occur in hypochlorhydric patients.