Serious toxicity associated with continuous nevirapine-based HAART in pregnancy.

OBJECTIVE: This study was designed to determine the safety of nevirapine (NVP)-based highly active antiretroviral therapy (HAART) in a cohort of HIV-positive pregnant women. DESIGN: This was a prospective cohort study of HIV-positive pregnant women. POPULATION AND SETTING: All HIV-positive women treated with HAART during pregnancy from January 1997 to February 2004 at the British Columbia (BC) Women's Hospital in Vancouver, BC, Canada. METHODS: Demographic and clinical data were collected to compare antiretroviral drug toxicities in women treated antenatally with NVP-based or non-NVP-based HAART. Multivariate analyses were then used to investigate determinants of toxicity. RESULTS: From 1997 to 2004, 103 HIV-positive pregnant women received HAART. Equivalent numbers of women were initially treated with NVP-based (54%) and non-NVP-based (46%) HAART. The groups did not differ by clinical or demographic parameters and duration of HAART exposure was similar between groups. Toxicities necessitating treatment discontinuation were observed in 6 of 56 NVP-exposed women (2 cases each of grade 2, 3, and 4 toxicity) compared with 1 of 47 in the non-NVP-exposed women. First time use of NVP approached significance as a predictor for toxicity, with a toxicity rate of 12.5% (6/48) observed among those taking NVP for the first time (adjusted OR 2.68, 95% CI 0.49-14.6). CONCLUSION: Continuous NVP use in pregnancy resulted in a relatively higher rate of toxicity, and all cases of NVP toxicity occurred in women exposed to NVP for the first time during pregnancy.

Ribavirin therapy of adult respiratory syncytial virus pneumonitis.

Respiratory syncytial virus is a common respiratory tract pathogen in infants. Pulmonary infection in adult and elderly populations can occur with severe and even fatal pneumonitis having been reported in several recent outbreaks. We present a previously healthy adult patient who developed respiratory syncytial virus pneumonia severe enough to require mechanical ventilation. Antiviral therapy with aerosolized ribavirin was successfully undertaken and the patient recovered completely. Respiratory syncytial virus infection should be considered in the differential diagnosis of atypical adult pneumonias. Aerosolized ribavirin therapy may be beneficial in treatment.

Case-control and vector studies of nosocomial acquisition of Pseudomonas cepacia in adult patients with cystic fibrosis.

OBJECTIVE: To examine factors associated with nosocomial acquisition of Pseudomonas cepacia in adult patients with cystic fibrosis. DESIGN: A retrospective case-control study of 5 patients with nosocomial acquisition of P cepacia versus 20 matched controls who failed to develop P cepacia infection. Selective handwashing, air sampling, and respiratory equipment sampling also were performed. SETTING: A university hospital providing tertiary care to 95 adult cystic fibrosis patients. PATIENTS: All patients are adults with known cystic fibrosis. Case definition required multiple negative sputum cultures for P cepacia prior to and during admission, with a positive sputum culture prior to discharge. Controls had negative sputum cultures for P cepacia prior to and throughout hospitalization. Controls were matched for age, gender, disease severity, and frequency of hospitalizations. RESULTS: Factors associated with increased risk of nosocomial acquisition of P cepacia included receiving humidifier or nebulized treatments (60% versus 5%, p = .016, odds ratio = 28.5, 95% confidence interval = 1.93 to 420.58). Factors without significance included ward, room, teaching versus nonteaching status, use of steroids, sharing a hospital room with another cystic fibrosis patient, antibiotic use, presence of portocath in situ, or socializing with another individual with cystic fibrosis known to be P cepacia-positive. Air sampling studies failed to demonstrate aerosolization of P cepacia by coughing cystic fibrosis patients over a 1-hour sampling time. Handwashing studies failed to demonstrate P cepacia on hands of cystic fibrosis patients, nurses, or physiotherapists (before or after physiotherapy). Reservoirs from nebulizers consistently grew P cepacia following therapy. CONCLUSIONS: Respiratory equipment may be an important source of nosocomial acquisition of P cepacia in adult cystic fibrosis patients.

Does Aeromonas hydrophila preferentially colonize the bowels of patients with hematologic malignancies?

Weekly cultures of stools from neutropenic patients and bone marrow transplant recipients yielded Aeromonas hydrophila from 8% of 88 patients over a 2-yr period. During this time stools in the routine enteric laboratory yielded A. hydrophila in 0.24% of 1632 patients. Although the patient groups and culture methods were not directly comparable, this significant difference in isolation rate (p less than 0.001) may reflect a higher colonization rate in the immunocompromised patient.

Human immunodeficiency virus infection in pregnancy.

The incidence and prevalence of human immunodeficiency virus (HIV) infection in women of child-bearing age continue to increase both internationally and in Canada. The care of HIV-infected pregnant women is complex, and multiple issues must be addressed, including the current and future health of the woman, minimization of the risk of maternal-infant HIV transmission, and maintenance of the well-being of the fetus and neonate. Vertical transmission of HIV can occur in utero, intrapartum and postpartum, but current evidence suggests that the majority of transmission occurs toward end of term, or during labour and delivery. Several maternal and obstetrical factors influence transmission rates, which can be reduced by optimal medical and obstetrical care. Zidovudine therapy has been demonstrated to reduce maternal-infant transmission significantly, but several issues, including the short and long term safety of antiretrovirals and the optimal use of combination antiretroviral therapy in pregnancy, remain to be defined. It is essential that health care workers providing care to these women fully understand the natural history of HIV disease in pregnancy, the factors that affect vertical transmission and the management issues during pregnancy. Close collaboration among a multidisciplinary team of knowledgeable health professionals and, most importantly, the woman herself can improve both maternal and infant outcomes.

Eradication of methicillin-resistant Staphylococcus aureus from the lower respiratory tract of patients with cystic fibrosis.

Two of 95 patients followed in an adult cystic fibrosis clinic consistently grew methicillin-resistant Staphylococcus aureus (mrsa) on sputum culture. Sputum Gram stain consistently showed +4 polymorphonuclear leukocytes and +4 Gram-positive cocci in clusters. Both patients were co-infected with Pseudomonas aeruginosa and required multiple hospitalizations for treatment of pulmonary exacerbation, resulting in significant infection control concerns. Multiple courses of antibiotics, including ciprofloxacin and clindamycin regimens, failed to eliminate the mrsa. A combination of oral rifampin and clindamycin was successful in eradicating the organism from both patients. Over a 12-month period following therapy, in both patients none of 13 sputums showed Gram-positive cocci in clusters on Gram stain and none of 13 sputum cultures grew mrsa. Successful eradication of mrsa has greatly simplified infection control measures on subsequent hospitalizations, reducing costs and enhancing patient comfort.

Bacteremic pneumonia caused by penicillin-resistant pneumococci: Case report and review with a Canadian perspective.

A Canadian adult with bacteremic pneumonia caused by a relatively penicillin-resistant (minimal inhibitory concentration 0.25 µg/mL) Streptococcus pneumoniae is reported, and the published literature regarding penicillin-resistant pneumococci in Canada reviewed. Although penicillin resistance has been reported infrequently to date, this case emphasizes the need for routine antimicrobial sensitivity testing of all pneumococci isolated from normally sterile sites, and for ongoing systematic surveillance for penicillin and other antibiotic resistance in Canada.

Histologically proven pressure sore-related osteomyelitis in the setting of negative technetium bone scans. Case report.

Pressure sores are common in patients with spinal cord injury, stroke or debilitating medical illness. Contiguous osteomyelitis is a well recognized complication of pressure ulcers, but remains a challenging diagnostic and management problem. Technetium bone scan is purported to be an extremely sensitive, although nonspecific diagnostic test for osteomyelitis. Indeed, a negative bone scan is thought to virtually exclude bone infection. We report three cases of pressure sore-related polymicrobial osteomyelitis where technetium bone scan was normal, yet bone biopsy demonstrated characteristic histopathologic changes of osteomyelitis. These cases raise questions regarding the sensitivity of bone scanning in the setting of pressure sores, and they demonstrate the need for further investigation into the correlation between nuclear medicine scan results and bone biopsy histopathology. Bone biopsy remains the gold standard for diagnosis of osteomyelitis, which can be present in bone underlying a pressure ulcer, even in the setting of a normal bone scan.

Lyme Disease: Review from a Canadian perspective.

Lyme borreliosis is an infectious disease caused by the tick-transmitted spirochete Borrelia burgdorferi. To date, the only known endemic focus of Lyme disease in Canada is Long Point, Ont. A national case definition for surveillance purposes, consensus statement regarding laboratory diagnosis, and treatment guidelines have recently been developed in an attempt to standardize the approach to surveillance, diagnosis, and management of Lyme borreliosis in Canada.

The Oak Tree Centre: initiatives for HIV-infected women, children, youth and families.

The Oak Tree Centre (Women and Family HIV Care Project) is designed to address the needs of women, youth, children and families affected by HIV infection in British Columbia. It is a conjoint project of the Women's Health Centre and British Columbia's Children's Hospital. Community involvement and the participation of individuals living with HIV infection continue to be vital components of the project. The ultimate goal is to enhance clinical and psychosocial care, and education, research and prevention initiatives for HIV-infected women, youth, children and families in British Columbia.

Gardnerella vaginalis-associated balanoposthitis.

The clinical features, microbiologic investigation, and response to therapy of three patients with Gardnerella vaginalis-associated balanoposthitis were studied. Each man presented with a similar syndrome of diffuse erythema and pruritus of the glans meatus and coronal sulcus, irritation of the prepuce, and minimal urethral discharge. A characteristic fishy odor was present in the urethral discharge of all three patients. G. vaginalis was isolated from the glans of all three, and clue cells were present in two. In all cases, cultures for Candida albicans, herpes simplex virus, Neisseria gonorrhoeae, Chlamydia trachomatis, and Ureaplasma urealyticum were negative. All three patients responded to oral therapy with metronidazole and concurrent treatment of the partner. Two patients subsequently relapsed but ultimately responded to clindamycin therapy. These men presented with a distinctive clinical syndrome of balanoposthitis associated with G. vaginalis, which is in many respects similar to the syndrome of bacterial vaginosis in women. Our data indicate that balanoposthitis may have a polymicrobial and synergistic etiology involving G. vaginalis and anaerobic bacteria in the male lower genital tract; such an etiology is analogous to that of bacterial vaginosis.

Experience at a referral center for patients with suspected Lyme disease in an area of nonendemicity: first 65 patients.

A multidisciplinary referral center was established at a university hospital for prospectively assessing patients with possible Lyme disease. Borrelia burgdorferi is not known to be endemic in this region, but considerable anxiety about Lyme disease has developed among the general public. Sixty-five patients were referred for suspected Lyme borreliosis. Detailed histories were obtained and physical examinations were performed; patients were investigated aggressively in accordance with their symptom complexes. Strict diagnostic criteria consistent with published standards were applied. Only two of the 65 patients were judged to have probable Lyme disease. Definite major alternate diagnoses were made for 50 patients (77%); firm medical diagnoses (11 dermatologic, 9 rheumatologic, 9 infectious disease, 6 gastrointestinal, 4 neurological, and 2 miscellaneous) were made for 41 patients (63%); and major psychiatric diagnoses were made for 9 patients (14%). Probable diagnoses of chronic fatigue syndrome and fibromyalgia were made for 11 patients (17%). The conditions of four patients (6%) were undiagnosed. A referral center for patients with suspected Lyme disease can be useful even in an area of nonendemicity, and careful clinical assessment will reveal treatable alternate diagnoses for many patients with suspected Lyme disease.

Feasible method for routine surveillance culturing of stools from neutropenic patients.

This study was undertaken to develop an accurate, yet inexpensive, method for determining whether the bowel of a neutropenic patient is colonized with bacteria resistant to the antimicrobial agents used in empiric therapy. Selective agar media were prepared in which Mueller-Hinton agar or MacConkey agar were supplemented with one of the following antimicrobial agents: carbenicillin (16 micrograms/ml), gentamicin (4 micrograms/ml), or tobramycin (4 micrograms/ml). Moxalactam was incorporated initially at 16 micrograms/ml and subsequently at 8 micrograms/ml. Stools from neutropenic patients and bone marrow transplant recipients were inoculated on these media and on unsupplemented MacConkey agar. All bacteria that grew on the antibiotic-containing media were categorized as resistant to the supplementing drug; failure to detect an organism that did grow on the antibiotic-free MacConkey agar indicated susceptibility. These results were compared with those obtained for all isolates on all media by agar disk diffusion. There were 512 gram-negative enteric isolates from 320 stools obtained from 98 patients. The antibiotic-containing media suppressed the growth of 95% of bacteria that were identified as susceptible by agar disk diffusion. In detecting resistant organisms, the correlation between agar disk diffusion and direct stool screening with Mueller-Hinton agar ranged from 73 to 83%, and on MacConkey agar it ranged from 87 to 97%. The predictive value of a resistant result was 80 to 97% for the four antimicrobial agents when MacConkey agar was used. MacConkey agar performed better than Mueller-Hinton agar because of the greater ease of detecting different bacterial morphotypes. The cost of direct stool screening with antibiotic-supplemented MacConkey agar is approximately half the cost of routine methods of surveillance. Its cost and accuracy make the method a useful adjunct to the routine management of neutropenic patients.

Neurotoxic effects during vidarabine therapy for herpes zoster.

Two cases of neurotoxic effects resulting from therapy with vidarabine are described. Both patients were undergoing treatment for cutaneously disseminated herpes zoster complicating therapy for solid malignant tumours. Both had normal renal function. The serum levels of hepatic enzymes were normal in one patient and slightly elevated in the other. Neurotoxicity was first manifested in both patients by the development of intention tremors that progressed to gross tremors. Obtundation, coma and death ensued in one patient and pain syndromes in the other. Vidarabine-induced neurotoxic effects, which may occur in the absence of hepatic or renal dysfunction or treatment with another drug, may be mild initially but may progress rapidly to more serious, even life-threatening, conditions. Presentation of neurotoxic effects should be considered an indication for withdrawal of vidarabine.

Septic arthritis due to dual infection with Mycoplasma hominis and Ureaplasma urealyticum.

Acute septic arthritis of a knee and shoulder developed in a 32-year-old renal transplant patient. Cultures yielded Mycoplasma hominis and at least 1, and possibly 2, strains of Ureaplasma urealyticum. Doxycycline therapy controlled the symptoms and signs, and the joints became culture negative. On stopping therapy after 7 months, the arthritis recurred and U. urealyticum was again isolated from the shoulder joint. Cessation of doxycycline almost 4 years after the initial episode resulted in another recurrence. To our knowledge, this is the 1st case in which both M. hominis and U. urealyticum have been isolated from a joint.

Xanthomonas maltophilia misidentified as Pseudomonas cepacia in cultures of sputum from patients with cystic fibrosis: a diagnostic pitfall with major clinical implications.

Pseudomonas cepacia infection in patients with cystic fibrosis (CF) has major significance in terms of infection control, psychosocial issues, and medical treatment. We describe three instances in which the diagnostic laboratory misidentified Xanthomonas maltophilia as P. cepacia in cultures of sputum from patients with CF. These errors were recognized when 3 (9%) of 32 isolates, which had all been identified as P. cepacia and had been submitted to the Canadian Pseudomonas Repository Laboratory (Vancouver, BC), were correctly identified there as X. maltophilia. Each of the three isolates grew well on P. cepacia media, turned a characteristic vivid pink color, were polymyxin-resistant, and were lysine-positive. All three were initially characterized incorrectly as oxidase-positive and DNase-negative. The diagnostic laboratory then reexamined 24 other isolates that had been identified as P. cepacia; complete biochemical testing confirmed that all were indeed P. cepacia. Because infection due to P. cepacia has major implications for patients with CF, when a possible strain of P. cepacia is isolated, careful and complete characterization should be performed.

Routine prenatal screening for HIV in a low-prevalence setting.

BACKGROUND: The objectives of this study were to assess the effect of British Columbia's June 1994 guidelines for prenatal HIV screening on the rate of maternal-fetal HIV transmission and to estimate the cost-effectiveness of such screening. METHODS: The authors conducted a retrospective review of pregnancy and delivery statistics, HIV screening practices, laboratory testing volume, prenatal and labour management decisions of HIV-positive women, maternal-fetal transmission rates and associated costs. RESULTS: Over 1995 and 1996, 135,681 women were pregnant and 92,645 carried to term. The rate of HIV testing increased from 55% to 76% of pregnancies on chart review at one hospital between November 1995 and November 1996. On the basis of seroprevalence studies, an estimated 50.2 pregnancies and 34.3 (95% confidence interval 17.6 to 51.0) live births to HIV-positive women were expected. Of 42 identified mother-infant pairs with an estimated date of delivery during 1995 or 1996, 25 were known only through screening. Of these 25 cases, there were 10 terminations, 1 spontaneous abortion and 14 cases in which the woman elected to carry the pregnancy to term with antiretroviral therapy. There was one stillbirth. One instance of maternal-fetal HIV transmission occurred among the 13 live births. The net savings attributable to prevented infections among babies carried to term were $165,586, with a saving per prevented case of $75,266. INTERPRETATION: A routine offer of pregnancy screening for HIV in a low-prevalence setting reduces the rate of maternal-fetal HIV transmission and may rival other widely accepted health care expenditures in terms of cost-effectiveness.