Prophylactic Isoniazid Research Articles

Reduced gut microbiota diversity in ulcerative colitis patients with latent tuberculosis infection during vedolizumab therapy: insights on prophylactic anti-tuberculosis effects

BackgroundThe gut microbiota plays a pivotal role in ulcerative colitis (UC) development. This study explores the impact of latent tuberculosis infection (LTBI) on the gut microbiota in UC and assesses changes during vedolizumab treatment, investigating prophylactic anti-tuberculosis therapy.ResultsThis cohort study included adult patients with UC receiving vedolizumab treatment at Jinhua Hospital, Zhejiang University from April 2021 to December 2022. Patients were divided into LTBI (n = 24) and non-LTBI (n = 21) groups. Patients in the LTBI group were further subdivided into prophylactic (n = 13) and non-prophylactic (n = 11) groups. Clinical and fecal samples were collected pre- and post-vedolizumab treatment for the LTBI groups and pre-treatment for the non-LTBI group. The gut microbiota was analyzed using 16 S rRNA sequencing. Patients in the non-LTBI group exhibited higher diversity indices. Vedolizumab demonstrated efficacy in the LTBI group, with clinical response and remission rates of 83.3% and 75.0%, respectively. The gut microbiota diversity in the LTBI group increased post-vedolizumab treatment, and receiving prophylactic isoniazid showed no significant difference in vedolizumab treatment response compared to not receiving prophylactic isoniazid. Microbiota changes were similar between groups, with an increase in [Ruminococcus] expression after vedolizumab treatment.ConclusionsThis cohort study, conducted at a single center, highlights that LTBI can reduce gut microbiota diversity among adult patient with UC. The observed efficacy of vedolizumab treatment in the LTBI group indicates a potential association with microbiota changes. However, mono-isoniazid exhibited limited impact, underscoring the potential of vedolizumab as a promising candidate for prophylactic anti-tuberculosis treatment in the context of UC.

Monitoring Adalimumab concentration, Adalimumab antibodies, fecal calprotectin, and QuantiFERON test positivity in patients with inflammatory bowel disease

<p><strong>Introduction.</strong> Inflammatory bowel diseases (IBD) are a serious global health problem affecting mostly younger and middle-aged persons. Despite the availability of variety of treatment approaches, the disease often progresses unpredictably. Biological drugs offer hope for IBD treatment. Our research share our preliminary findings regarding the monitoring of adalimumab (ADM) and adalimumab antibodies (ADA) concentrations, fecal calprotectin levels, and the frequency of QuantiFERON test positivity in IBD patients treated with biological drugs.<strong> </strong></p> <p><strong>Methods.</strong> The study was designed as a retrospective, descriptive, single-center study and was conducted at the University Clinical Center of the Republic of Srpska, Banja Luka, from January 2018 to June 2022. Medical records of patients treated at the Internal Medicine Clinic were analyzed. Patients were categorized based on underlying disease and duration of biological therapy. ADM and ADA concentrations were monitored at intervals, and QuantiFERON test positivity and fecal calprotectin levels were recorded. Statistical methods, including analysis of Variance (ANOVA) and paired t-test were performed using the SPSS program version 29.</p> <p><strong>Results.</strong> Medical records of 117 patients were analyzed. Most of them, 44 were treated with adalimumab. Male patients were predominant (59.10%) in our study over females. Patients were also categorized based on the length of biological therapy. ADM and ADA concentrations increased with time (after 6, 12, 18 and 24 months), but without statistical significance. Fecal calprotectin levels decreased after 12 and 24 months of treatment. Out of the total number of patients, 53.83% of QuantiFERON positive patients were treated with adalimumab. Prophylactic isoniazid therapy was carried out in 63.6% of patients.</p> <p><strong>Conclusion. </strong>Our initial experience in monitoring biological drug concentrations and fecal calprotectin levels in IBD patients showed a decrease in fecal calprotectin levels and an increase in ADM and ADA concentrations over time but there were no statistically significant differences.</p>

Tuberculosis Exposure from a Healthcare Worker to Patients in a Neonatal Intensive Care Unit (NICU).

The nosocomial spread of Mycobacterium tuberculosis from a healthcare worker with infectious pulmonary tuberculosis disease to patients remains a risk in the healthcare environment, including neonatal intensive care units. In this paper, we outlined a protocol for neonates exposed to tuberculosis in a neonatal intensive care unit that includes skin testing, chest X-ray imaging, and prophylactic isoniazid. Neonatal patients were followed up with tuberculosis skin testing at both three months corrected age and two months postexposure. To our knowledge, this is the first Canadian study to illustrate a protocol following tuberculosis exposure in a neonatal intensive care unit for exposed neonates.

Efficacy and safety of ustekinumab in the treatment of moderate to severe plaque psoriasis in Singapore.

Ustekinumab is a human monoclonal antibody that binds to the p40 subunit of both interleukin (IL)-12 and IL-23, and it is approved for the treatment of moderate to severe plaque psoriasis. In this study, we assessed the efficacy and safety of patients receiving ustekinumab for psoriasis. This retrospective study included all adults with chronic plaque psoriasis who were prescribed ustekinumab in a tertiary dermatologic centre between December 2009 and December 2015. Efficacy end points included a proportion of patients achieving at least 50% and 75% improvement from baseline psoriasis area and severity index (PASI) and body surface area (BSA) at Weeks 4 and 16. A total of 99 patients were prescribed ustekinumab; 69% of these were Chinese, followed by 15% Indians and 9% Malays. 31 patients had documented PASI scores and 55 patients had documented BSA improvements. In patients with recorded PASI scores, 29 (93.5%) of 31 patients achieved PASI 50, and 21 (67.7%) of 31 achieved PASI 75 at week 16. In patients with recorded BSA, 43 (78.2%) of 55 had at least 50% BSA improvement, and 31 (56.4%) of 55 achieved 75% BSA improvement at 16 weeks. Regarding safety, no patient experienced tuberculosis reactivation. A total of 11 (11%) of 99 patients had latent tuberculosis infection and were treated with prophylactic isoniazid. No patient experienced serious adverse events. No cardiovascular events, cutaneous malignancies or deaths were reported over six years. Ustekinumab is safe and efficacious in the treatment of patients with moderate to severe plaque psoriasis in a multiethnic Asian population.

Tuberculin test conversion in patients with chronic inflammatory arthritis receiving biological therapy.

ObjectiveThe blockade of inflammatory mediators produced by biological therapies is associated with an increased risk of opportunistic infections, as for example Mycobacterium tuberculosis (MT). Given the endemic situation of tuberculosis (TB) in some countries and immunosuppression/anergy of patients with chronic inflammatory arthritis, we wonder whether it is necessary to monitor the MT infection after starting the biological treatment. To evaluate the frequency of the tuberculin skin test (TST) conversion and its association with an active TB infection and other disease variables.MethodsPatients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and spondyloarthritis (SpA) receiving treatment with anti-TNF, tocilizumab, and/or abatacept agents were included into the study. Patients had to have a negative TST (<5 mm) at the baseline, and a second TST was performed 2–22 months after the initiation of biologic therapy. The TST conversion was considered as a variation ≥5 mm between the two TSTs performed within an interval between 2 months and 2 years.ResultsA total of 85 patients were included into the study, and 78.8% were women, with a median schooling duration of 12 years. A total of 74.1% of patients had RA, 16.5% psoriatic arthritis, and 4.7% AIJ and ankylosing spondylitis. Regarding treatment, 75.3% received anti-TNF therapy (31.8% etanercept, 21.2% adalimumab, 17.6% infliximab, 3.5% golimumab, and 1.2% certolizumab), 15.3% tocilizumab, and 9.4% abatacept. Eight patients (9.4%) developed a TST conversion. The shift was more frequent in men (62.5%) than in women (37.5%) (p=0.009), and in those with a prolonged disease duration (X 226±109 vs X130±105 [p=0.017]). This association remained after adjusting for other variables. All patients who developed a TST conversion received prophylactic isoniazid, and only one patient with other risk factors developed active TB.ConclusionThe frequency of a TST conversion in patients with chronic inflammatory arthritis was low and was associated with male gender and longer disease duration.

Correlates of adherence and utilization of Isoniazid preventive therapy in HIV patients

Objective: Isoniazid (INH) is given to individuals with latent infection of tuberculosis in order to prevent progression to active disease. It is important to understand factors associated with non-adherence to prophylactic Isoniazid. This study aimed to identify correlates of adherence and utilization of Isoniazid in HIV positive patients and to explore the opinions of patients and health care providers. Methods: Participants eligible for the study were 403 randomly selected HIV positive individuals taking INH on follow up in Yekatit 12 hospital. Adherence was measured by self-report of INH tablets taken for past 3, 7 and 30 days. In depth interview was also conducted on recruited patients and health professionals. Results: Adherence to INH was 94% for last 7 days. INH related common side effects were reported by 142 participants (35.2%) and only 53 (13.2%) discontinued. The odds of adherence was 104, 7.7 and 34.8 [95% Confidence Interval (18.7, 582.6), (2.6, 22.9) and (4.4, 272.6)] times higher among those patients who did not have jaundice, skin rash and seizure compared to those who developed, respectively. Conclusion: The prevalence of adherence to INH in Yekatit 12 hospital was better than other local and African studies and the reasons for poor adherence was strongly associated with occurrence of jaundice, skin rash and seizure. Com­prehensive care and support, sustainable drug supply and evaluation of side effects are recommended. J Microbiol Infect Dis 2015;5(2): 45-50 Key words: Tuberculosis; HIV; adherence, Isoniazid, preventive therapy, side effects

Successful treatment with infliximab despite positive tuberculosis ELISpot results in a patient with pityriasis rubra pilaris taking prophylactic isoniazid

Clinical and Experimental DermatologyVolume 36, Issue 7 p. 808-809 Viewpoints in dermatology • Correspondence Successful treatment with infliximab despite positive tuberculosis ELISpot results in a patient with pityriasis rubra pilaris taking prophylactic isoniazid M. Zirbs, M. Zirbs Department of Dermatology and Allergy Clinic and Polyclinic for Dermatology and Allergology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Biedersteinerstraβe 29, Muenchen, GermanyE-mail: michael.zirbs@lrz.tu-muenchen.deSearch for more papers by this authorE. Kigitsidou, E. Kigitsidou Department of Dermatology and Allergy Clinic and Polyclinic for Dermatology and Allergology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Biedersteinerstraβe 29, Muenchen, GermanyE-mail: michael.zirbs@lrz.tu-muenchen.deSearch for more papers by this authorF. Seifert, F. Seifert Department of Dermatology and Allergy Clinic and Polyclinic for Dermatology and Allergology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Biedersteinerstraβe 29, Muenchen, GermanyE-mail: michael.zirbs@lrz.tu-muenchen.deSearch for more papers by this authorJ. Ring, J. Ring Department of Dermatology and Allergy Clinic and Polyclinic for Dermatology and Allergology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Biedersteinerstraβe 29, Muenchen, GermanyE-mail: michael.zirbs@lrz.tu-muenchen.deSearch for more papers by this authorK. Brockow, K. Brockow Department of Dermatology and Allergy Clinic and Polyclinic for Dermatology and Allergology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Biedersteinerstraβe 29, Muenchen, GermanyE-mail: michael.zirbs@lrz.tu-muenchen.deSearch for more papers by this author M. Zirbs, M. Zirbs Department of Dermatology and Allergy Clinic and Polyclinic for Dermatology and Allergology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Biedersteinerstraβe 29, Muenchen, GermanyE-mail: michael.zirbs@lrz.tu-muenchen.deSearch for more papers by this authorE. Kigitsidou, E. Kigitsidou Department of Dermatology and Allergy Clinic and Polyclinic for Dermatology and Allergology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Biedersteinerstraβe 29, Muenchen, GermanyE-mail: michael.zirbs@lrz.tu-muenchen.deSearch for more papers by this authorF. Seifert, F. Seifert Department of Dermatology and Allergy Clinic and Polyclinic for Dermatology and Allergology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Biedersteinerstraβe 29, Muenchen, GermanyE-mail: michael.zirbs@lrz.tu-muenchen.deSearch for more papers by this authorJ. Ring, J. Ring Department of Dermatology and Allergy Clinic and Polyclinic for Dermatology and Allergology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Biedersteinerstraβe 29, Muenchen, GermanyE-mail: michael.zirbs@lrz.tu-muenchen.deSearch for more papers by this authorK. Brockow, K. Brockow Department of Dermatology and Allergy Clinic and Polyclinic for Dermatology and Allergology, Klinikum Rechts der Isar, Technische Universitaet Muenchen, Biedersteinerstraβe 29, Muenchen, GermanyE-mail: michael.zirbs@lrz.tu-muenchen.deSearch for more papers by this author First published: 20 April 2011 https://doi.org/10.1111/j.1365-2230.2011.04074.xCitations: 10 Conflict of interest: none declared. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume36, Issue7October 2011Pages 808-809 RelatedInformation

Infections after Lung Transplantation

Despite advances in prophylaxis and therapy, infections remain a major source of morbidity and mortality after lung transplantation. Lung transplant recipients are at increased risk for both community-acquired and nosocomial pathogens, which may develop at various time points. The risk of infections increases with the intensity of immunosuppression. Careful assessment of the recipient is essential to assure adequate prophylactic or preemptive therapy. Aggressive prophylaxis for some infections (e.g., cytomegalovirus) has substantially reduced the prevalence of serious infections due to this organism. Tuberculin-positive individuals should be treated with prophylactic isoniazid to reduce the chance for reactivation of tuberculosis following transplantation. Myriad opportunistic pathogens (including various viruses, bacteria, fungi, etc.) may complicate transplantation, owing to the effects of multiagent immunosuppressive therapy. This review addresses the salient pathogens that may infect organ transplant recipients, and discusses strategies to prevent or treat specific pathogens in this highly susceptible patient population.

Tuberculin skin test conversion and reactivity rates among adults with and without human immunodeficiency virus in urban settings in Ethiopia.

To investigate whether low CD4+ T-cell counts in healthy and human immunodeficiency virus (HIV)-infected Ethiopians influence tuberculosis (TB) immunological memory, tuberculin skin test (TST) conversion and reactivity rates were investigated among adults with and without HIV infection in urban settings in Ethiopia. Reaction to the TST was analyzed with purified protein derivative by the Mantoux technique. A total of 1,286 individuals with TST results of > or = 5-mm (n = 851) and < or = 4-mm (n = 435) induration diameters were included. Individuals with < or = 4-mm induration sizes were followed up for 21.4 +/- 9.5 months (mean +/- standard deviation) to observe skin test conversion. The overall TST reactivity (> or = 5-mm induration diameter) was 66.2% (n = 851). Reactivity was significantly lower among HIV-positive persons (40.5%) than among HIV-negative persons (68.7%) (P < 0.001). Of the above persons, 32 incident TB patients were checked for their TST status 13.05 +/- 11.1 months before diagnosis and reactivity was found among 22 (68.7%) of them. Of the TST-negative persons with 0- to 4-mm indurations who were followed up for 3 years, the conversion rate to positivity was 17.9/100 person-years of observation (PYO) (14.4/100 PYO and 18.3/100 PYO in HIV-positive and -negative persons, respectively). Despite lower absolute CD4+ T-cell numbers in Ethiopians, higher TST conversion and reactivity rates show the presence of a higher rate of latent TB infection and/or transmission. The lower TST positivity rate before a diagnosis of TB disease showed the lower sensitivity of the test. This indicates the need for other sensitive and specific diagnostic and screening methods to detect TB infection, particularly among HIV-positive persons, so that they can be given prophylactic isoniazid therapy.

BCG: The Optimal Approach in Superficial Bladder Cancer

Accessible online at: www.karger.com/journals/eur Floor: Dr Rischmann recommends urine culture if fever persists following BCG installation. Would not blood culture for mycobacteria also be appropriate if you are concerned about systemic BCG septicaemia? P. Rischmann: If fever and side-effects such as cystitis are moderate, then you should proceed with urine culture. While waiting for the results, fluoroquinolones and paracetamol can be given. In the case of severe systemic effects, one should not wait for bacteriological results before beginning treatment. Blood cultures are seldom positive; reverse-transcriptase-PCR may be more useful. A. Bohle: From our own experience, and from the experience in the literature, blood cultures are not very successful at revealing mycobacterial infection. Blood cultures are often negative even in the presence of systemic BCG infection. Floor: Is any of the various BCG strains superior? Furthermore, when referring to reductions in the dose of BCG, does it make more sense to talk about colony-forming units (CFUs) rather than milligrams? Equal doses (in milligrams) of different strains of BCG may have different numbers of CFUs. P.F. Bassi: Which parameters we use to measure BCG is an important topic, but one that is still largely unexplored. As a matter of fact, we do not know what the active component of the BCG is or how BCG works. As a consequence, we do not know what to measure: weight is only a manufacturer’s product information, which does not express the absolute therapeutic ability of the preparation. It is, therefore, not possible to make a comparison by weight between, for example, 150 mg of Pasteur BCG, 81 mg of Connaught BCG or 50 mg of OncoTice. Consequently, it is impossible to say that 150 mg Pasteur BCG is threefold ‘better’ than 50 mg Tice strain. Also the number of viable colonies (CFUs) has been supposed, in the past, to make a difference in terms of efficacy, but in the long run, this highly imprecise parameter has failed to be a reliable indicator. D.L. Lamm: The variability not only between strain and strain, but also between one ampoule and another ampoule of the same preparation is very high. For this reason, Mike O’Donnell’s recommendation for dose reduction makes a lot of sense, and in our experience is very useful. When patients start to have increased side-effects we reduce the dose to one third; if side-effects persist or increase, the dose is reduced to one tenth, and even to one hundredth if necessary. Basically, the patient does not have to suffer at all to receive effective immune stimulation with BCG, and I think that dose reduction therefore really makes more sense than prophylactic isoniazid. With isoniazid we are adding another variable, and we don’t know what percentage kill isoniazid prophylaxis results in, unlike log reductions in BCG dose, which do give us a rough idea of the effective decrease in dose. Floor: Do you think there is any correlation between the pre-treatment tuberculin test and the subsequent development of side-effects?

PID17: DETERMINATION OF THE COST-EFFECTIVENESS OF A TUBERCULOSIS PREVENTION PROGRAM ALONG THE US/ MEXICO BORDER USING MARKOV PROCESS MODELING WITHIN A PREVENTION EFFECTIVENESS FRAMEWORK

A prevention effectiveness analysis framework was used to estimate the costefifectiveness of a county administered tuberculosis prevention program along the U.S. / Mexico border. The tuberculosis prevention program under study used prophylactic isoniazid therapy in patients who have tested positive for tuberculosis infection. This analysis determined the cost-effectiveness of the current program versus no program from the perspective of the county government and was modeled for two time periods; five years and 15 years post preventive therapy initiation. Costs were calculated using actual data from tuberculosis prevention and active tuberculosis treatment programs as well as hospital discharge data. The outcome of interest, cases of active tuberculosis averted, was calculated through a Monte Carlo simulated Markov process model. Average and incremental cost-effectiveness ratios were then calculated for the tuberculosis prevention program scenario. The cost-effectiveness ratios were calculated separately with the inclusion or exclusion of the tuberculosis contagion costs. The results of the cost-effectiveness ratio calculations established that the prevention of active tuberculosis cases with the tuberculosis prevention program is considerably cost-effective. Every baseline incremental cost-effectiveness ratio, across the five and 15 year analysis periods (irrespective of contagion costs) determined in this prevention effectiveness study demonstrated cost savings. Additionally, the cost savings were substantial. The results indicate that rather than incurring costs to avert active

Bacille Calmette-Guérin in superficial transitional cell carcinoma.

The mechanisms by which BCG exerts its antitumour activity remain unclear. Attachment of BCG to the bladder via FN has been shown to be an important step in initiating its antitumorigenic activity. The mechanism(s) by which BCG operates requires LAK cells, BCG-activated killer cells, T lymphocytes (CD4) helper cells and CD8 suppressor/cytotoxic cells) and monocytes. The optimal route of administration is intravesical. The efficacy of a BCG vaccine depends on the viability, dose and strain. Differences in efficacy and side-effects have not been shown between different strains. Low-dose regimens successfully protect from recurrences, with fewer side-effects. The initial schedule of BCG is a course of six instillations in 6 weeks; when the patient fails this course, two possibilities arise. The first is maintenance therapy; response rates improve but there is more local and systemic toxicity. The second is a further 6-week course, and this seems most useful in those with a sustained response to the initial treatment. The clinical response to BCG therapy can be monitored using cytokine measurements or p53 determinations. Toxicity remains a major problem in BCG treatment and triple antituberculosis combination therapy should be given for 3 months in those with severe systemic side-effects. The use of prophylactic isoniazid is not recommend to decrease side-effects. The clinical results of BCG have been good, with success rates of 58-100%, with a minimal follow-up of one year in prophylaxis. BCG seems superior to intravesical therapy, but at the cost of inducing more adverse effects. BCG is not indicated for low- and intermediate-risk patients, in whom chemotherapy is the first choice. BCG can also be used to eliminate tumour after an incomplete TUR, or in patients who are unfit for surgery, with a 60-70% success rate. The primary and best treatment for CIS is intravesical BCG; encouraging results have been reported, with success rate of 42-83% after a minimal follow-up of one year. Although currently BCG seems to be the choice for high-risk superficial TCC, many questions remain unanswered, especially about the mechanism(s) of action, the optimal dose and clinical schedule.

The Cost-effectiveness of Preventing Tuberculosis in Physicians Using Tuberculin Skin Testing or a Hypothetical Vaccine

Tuberculin skin testing using the purified protein derivative is recommended as part of a tuberculosis control program for health care workers. However, compliance with skin testing programs has been poor and their cost-effectiveness is unknown. A Markov-based decision analysis was performed to determine the cost-effectiveness of tuberculin skin testing over the entire lifetimes of physicians who are now in medical school. Assumptions were deliberately chosen to present a conservative estimate of cost-effectiveness. Indirect costs were not included. Annual testing cost $29,000 per life-year saved and $39,000 per case of pulmonary tuberculosis prevented. In contrast, particulate respirators have been shown to cost millions of dollars per case prevented. Skin testing every 6 months was cost-effective in a subpopulation at high risk of infection (> or = 1.8-fold). During their entire lifetimes, physicians now in medical school can expect to avert 137 cases of pulmonary tuberculosis, prevent 7 tuberculosis deaths, and save 182 life-years because of skin testing programs. Improved compliance with annual skin testing and prophylactic isoniazid could more than triple this benefit. If available, a moderately effective vaccine would be even more cost-effective than tuberculin skin testing programs. Tuberculin skin testing is cost-effective and should be an integral part of any tuberculosis control program. Vaccination may one day be a feasible and cost-effective alternative to skin testing programs.

Does Isoniazid Reduce Side Effects of Intravesical Bacillus Calmette-Guerin Therapy in Superficial Bladder Cancer? Interim Results of European Organization for Research and Treatment of Cancer Protocol 30911

We analyzed the influence of the tuberculostatic agent isoniazid on the incidence and severity of adverse effects of intravesical bacillus Calmette-Guerin (BCG) therapy in patients with superficial bladder cancer. In a prospective randomized multicenter study the side effects of intravesical instillations with Tice strain BCG with and without isoniazid were compared in patients with stages pTa and pT1 bladder tumors. Isoniazid was given orally at a dose of 300 mg. daily at every instillation in an attempt to decrease the side effects of BCG. No differences in local or systemic adverse reactions after intravesical immune therapy with BCG could be observed between patients treated with or without prophylactic isoniazid therapy. However, analysis of liver function tests after BCG with isoniazid showed slightly more liver toxicity compared to BCG alone. Prophylactic administration of isoniazid during BCG instillations provides no decrease in any known side effect of BCG. In contrast, transient liver function disturbances are encountered slightly more frequently when isoniazid is administered. The use of prophylactic isoniazid in patients treated with BCG is not recommended.

Quality in HIV/AIDS Care Specialty-Related or Experience-Related?

In this issue, Markson et al. describe the characteristics of New York state clinics caring for Medicaid- enrolled outpatients with a new AIDS diagnosis between 1987–92.1 Their work is interesting because these descriptions can be used to measure the process of care provided by various types of clinics. Results suggest that HIV/AIDS-dedicated and infectious disease clinics provide better care than community-based primary care clinics, which in turn provide better care than hospital-based general medicine clinics. While they did not measure clinical outcomes or the costs of care, Markson and colleagues do reference a literature that supports the connection between improved outcomes and the process of care, including for example, access to care and the availability of comprehensive services. Given these results, one might reasonably reconsider the proposition that HIV/AIDS care is best provided by generalists.2

Management of common respiratory problems

This article reviews the clinical management of common respiratory illnesses that primary care providers encounter in an out-patient setting. The latest recommendations from the American Thoracic Society, the National Heart, Lung, and Blood Institute, and the Centers for Disease Control and Prevention are summarized. The article discusses the causative organisms and antibiotics of choice for community-acquired pneumonia, and how to determine which patients require hospitalization. The appropriate use of asthma medications is described in detail, along with strategies for reducing aeroallergen exposure and for educating patients. An extensive section covers the interpretation of tuberculin skin tests and use of prophylactic isoniazid for preventive therapy of latent tuberculosis infection, as well as the treatment of active tuberculosis. Controversies regarding antibiotics for both acute and chronic bronchitis are discussed, along with other treatment options including over-the-counter medications, bronchodilators, and non-pharmacologic interventions. Finally, a strategy for dealing with the compliant of chronic cough is outlined. Although many of these conditions require active comanagement by collaborating physicians, the nurse-midwife will be better able to communicate with and advocate for her clients if she possesses expanded and current knowledge of treatment strategies.

Physicians' Ability to Provide Initial Primary Care to an HIV-Infected Patient

Primary care physicians are providing care for an increasing number of persons infected with the human immunodeficiency virus (HIV). This study assesses the ability of primary care physicians to provide initial care for a patient with recently diagnosed HIV infection. A standardized patient (SP) was trained to portray an asymptomatic person with HIV infection seeking a primary care physician. Physicians took a medical history and counseled the SP; their performances were assessed by the SP and through a brief written examination. In addition, physicians distributed questionnaires to HIV-infected patients in their practices to assess actual performance. The study participants consisted of 121 primary care physicians. A minority of physicians recommended standard primary care screening tests and vaccinations, including viral hepatitis screening (35%), syphilis serologic testing (32%), and pneumococcal vaccination (23%). While most physicians (87%) indicated they would obtain CD4 cell counts, only 50% indicated they would start appropriate Pneumocystis carinii pneumonia prophylaxis. Although this patient presented documentation of a positive tuberculin skin test and no prior therapy for tuberculosis, only 53% of the physicians recommended prophylactic isoniazid. While 75% of the physicians asked this SP about condom use, number of sexual partners, or contact with previous sexual partners. Physicians with the most HIV experience were more likely to recommended P carinii pneumonia prophylaxis, coinfection screening, pneumococcal vaccination, and isoniazid prophylactic therapy. However, physicians' HIV experience was not associated with assessing this SP's risk of infecting others or with counseling regarding condom use. Questionnaires distributed to HIV-infected patients of these physicians generally confirmed these findings. Basic HIV preventive and primary care may not be adequately performed by many primary care physicians. Physicians' HIV experience was associated with better performance of HIV primary care tasks, but not with screening and counseling concerning the spread of HIV infection.

Multidrug-resistant tuberculosis: meeting the challenge.

Both public and private institutions are mobilizing to combat drug-resistant TB--indeed, to eliminate all TB. Meeting this goal will require a three-pronged approach: 1) prophylactic isoniazid treatment of latent TB, 2) multidrug (at least six agents in some cases) treatment of active TB to eradicate resistant strains, and 3) correction of the social conditions that have contributed to the current epidemic.

Priorities for HIV testing in developing countries?

The specificity and sensitivity of human immunodeficiency virus (HIV) antibody tests have increased and their use has expanded in developed and developing countries since 1985. Lately, more expensive rapid (US $3-12/test) and cheaper HIV tests have been proposed. HIV testing by the inexpensive enzyme-linked immunosorbent assays (ELISAs) is often infeasible in developing countries because of the lack of equipment. In 1990, in Kinshasa, Zaire, only about 50% of blood donors were screened for HIV. Counseling before and after testing at centers sponsored by non-governmental organizations is limited in developing countries. HIV testing can lead to discrimination: people have been put in quarantine because they were found to be HIV positive. In regions of high prevalence, high priority testing for blood transfusion is cost beneficial. A positive HIV test would justify the start of treatment for toxoplasmosis in a patient with a focal neurological deficit. In a region of high HIV prevalence, a patient with chronic diarrhea would benefit more from an HIV test than from gastroenterological tests. The absence of facilities for CD4 cell counting makes it impossible to advise symptom-free HIV infected subjects. Prophylactic isoniazid may decrease the incidence of Mycobacterium tuberculosis infection among HIV-infected people but the potential for non-compliance with treatment and the risk that drug resistance will develop exist. Confidential HIV testing plus counseling and condom promotion decreased the incidence of HIV infection and gonorrhea among women living in Kigali, Rwanda. There has been successful counseling of discordant couples with HIV infection in Kigali, Rwanda, and Kinshasa, Zaire. HIV testing in the most cost-beneficial way should be done for both members of a steady couple at the same time. HIV tests should be more available in developing countries, and national guidelines for HIV testing should be set.

COMPLICATIONS OF BACILLUS CALMETTE-GUÉRIN IMMUNOTHERAPY

Knowing when to give and when to withhold BCG will prevent most complications, but even when all precautions are taken, some complications will occur. The initial step in the treatment of infectious complications is the use of isoniazid. Routine prophylactic isoniazid should not be given, as animal studies have confirmed that immune stimulation, and presumably antitumor activity, can be inhibited by isoniazid prophylaxis. However, when cystitis persists more than 2 days or is so severe that it does not respond to symptomatic treatment, isoniazid 300 mg daily is used to control the symptoms, prevent progressive infection, and avoid the overgrowth of BCG, which can result in excessive organisms and suppression of the immune response. If symptoms progress despite isoniazid treatment or do not begin to abate within 1 to 2 weeks, rifampicin 600 mg daily is added. Rifampicin is given from the beginning in patients with potentially severe extravesical BCG infection such as pneumonitis, hepatitis, or nephritis. In patients with symptoms such as fever, malaise, or bladder irritation that respond within a few days, it generally is necessary to continue antitubercular antibiotics for only 2 weeks. Those with extravesical infection and those who do not respond promptly to treatment are treated for 3 months, and those with severe or deep-seated infection are treated for 6 months. The current recommendation for the treatment of sepsis after BCG administration, based on limited clinical experience and controlled animal experimentation, is to use isoniazid and rifampicin plus prednisolone 40 mg daily.(ABSTRACT TRUNCATED AT 250 WORDS)