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BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Background: Applicants seeking entry into the United States are examined overseas for TB by panel physicians and international immigration clinicians guided by Centers for Disease Control and Prevention (CDC) TB Technical Instructions. To support this effort, CDC-funded TB Centers of Excellence (COEs) provide web-based expert consultation, with documentation stored in a medical consultation database (MCD). MCD analysis can reveal inquiry trends among panel physicians worldwide., Methods: TB-related queries in the COE MCD from January 1, 2018, to December 31, 2022, were analyzed using a descriptive coding scheme developed through inductive analysis, allowing multiple themes per entry., Results: A total of 215 queries from 126 patients in 28 countries were analyzed. Major themes included evaluating diagnostic criteria, tailoring treatment, and managing comorbidities or adverse reactions. Diagnostic questions ( n = 104, 48.4%) included mycobacterial culture, smear, and radiology interpretation. Treatment tailoring inquiries involved optimizing the initial regimen ( n = 89, 41.4%) or modifying existing regimens ( n = 26, 12.1%). Additionally, 50 consultations (23.2%) mentioned comorbidities, while 47 (21.9%) described adverse reactions., Conclusion: The MCD analysis identified topics where TB expertise was provided in overseas medical evaluation. These topics highlight opportunities for targeted panel physician education to improve the health of individual applicants and advance U.S. TB elimination efforts., Competing Interests: Conflict of interest: none declared., (© 2024 The Authors.)

In December 2022 World Health Organization released a new treatment for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) guideline. The main novelty of this update is two new recommendations (i) a 6-month treatment regimen composed of bedaquiline, pretomanid, linezolid (600 mg), and moxifloxacin (BPaLM) is recommended in place of the 9-month or longer (18-month) regimens in MDR/RR-TB patients, now including extensive pulmonary TB and extrapulmonary TB (except TB involving central nervous system, miliary TB and osteoarticular TB); (ii) the use of the 9-month all-oral regimen rather than longer (18-months) regimen is suggested in patients with MDR/RR-TB and in whom resistance to fluoroquinolones has been excluded. Longer (18-month) treatments remain a valid option in all cases in which shorter regimens cannot be implemented due to intolerance, drug-drug interactions, extensively drug-resistant tuberculosis, extensive forms of extrapulmonary TB, or previous failure. The new guidelines represent a milestone in MDR/RR-TB treatment landscape, setting the basis for a shorter, all-oral, more acceptable, equitable, and patient-centered model for MDR/RR-TB management. However, some challenges remain to be addressed to allow full implementation of the new recommendations., Competing Interests: Declaration of competing interests Tiberi S. is an employee of GSK, all opinions are his own and not that of the company. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening condition needing long poly-chemotherapy regimens. As no systematic reviews/meta-analysis is available to comprehensively evaluate the role of delamanid (DLM), we evaluated its effectiveness and safety., Methods: We reviewed the relevant scientific literature published up to January 20, 2022. The pooled success treatment rate with 95% confidence intervals (CI) was assessed using a random-effect model. We assessed studies for quality and bias, and considered P<0.05 to be statistically significant., Results: After reviewing 626 records, we identified 25 studies that met the inclusion criteria, 22 observational and 3 experimental, with 1276 and 411 patients, respectively. In observational studies the overall pooled treatment success rate of DLM-containing regimens was 80.9% (95% CI 72.6-87.2) with no evidence of publication bias (Begg's test; P >0.05). The overall pooled treatment success rate in DLM and bedaquiline-containing regimens was 75.2% (95% CI 68.1-81.1) with no evidence of publication bias (Begg's test; P >0.05). In experimental studies the pooled treatment success rate of DLM-containing regimens was 72.5 (95% CI 44.2-89.8, P <0.001, I 2 : 95.1%) with no evidence of publication bias (Begg's test; P >0.05)., Conclusions: In MDR-TB patients receiving DLM, culture conversion and treatment success rates were high despite extensive resistance with limited adverse events., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: In 2019, the World Health Organization released guidelines reflecting major changes in multidrug-resistant tuberculosis (MDR-TB) management-prioritizing fluoroquinolones, bedaquiline, and linezolid (LZD) while de-emphasizing previously favored injectable agents. In some cases, linezolid use is associated with gastrointestinal intolerance, mitochondrial toxicity, and significant drug interactions. CDC's Division of Tuberculosis Elimination supports a network of regional TB Centers of Excellence, which provide medical consultation to healthcare providers. Consultations are documented in a medical consultation database (MCD) enabling evaluation of management questions and recommendations. We describe the scope of clinical inquiries and responses specific to linezolid use for MDR-TB in the US., Research Question: What are the major themes of provider and patient challenges regarding the use of linezolid for the treatment of MDR-TB in the US?, Methods: We queried MCD consults categorized as "MDR/XDR-TB" from 1/1/2013 to 12/31/2018. Only linezolid-specific consultations were included; incomplete and duplicate entries were excluded as were those citing linezolid historically or theoretically. Subgroup characteristics were assessed (e.g., Center, year, provider type). A descriptive coding scheme was developed through inductive thematic analysis., Results: In 2013-2018 of the 1889 consults regarding MDR/XDR-TB, 934 MDR-TB consults referenced linezolid; 137 met inclusion criteria, representing between 4 and 10% of MDR-TB consults annually. Four main themes emerged: adverse effects (71.5%); concerns about linezolid use due to co-morbidities or concurrent medication use (15.3%); dosing adjustments (8.8%); and monitoring and maintenance logistics (4.4%)., Interpretations: Linezolid consults consistently exceeded 4% of all consults annually over the 6-year period, suggesting a need for access to expert opinion for providers using linezolid to manage MDR-TB. While only a snapshot of MDR-TB in the US, this evaluation summarizes major provider concerns regarding particular adverse effects, and highlights a need for evidence-based guidance regarding linezolid dosing and toxicity management., (© 2020 The Authors.)

Background: In 2012, the Food and Drug Administration approved use of bedaquiline fumarate as part of combination therapy for multidrug-resistant tuberculosis (MDR TB). We describe treatment outcomes, safety, and tolerability of bedaquiline in our case series., Methods: Data on patients started on bedaquiline for MDR TB between September 2012 and August 2016 were collected retrospectively through 4 TB programs using a standardized abstraction tool. Data were analyzed using univariate methods. Adverse events were graded using the Common Terminology Criteria for Adverse Events., Results: Of 14 patients, 7 (50%) had MDR, 4 (29%) had pre-extensively drug-resistant (XDR), and 3 (21%) had XDR TB. All had pulmonary TB, 5 (36%) had pulmonary and extrapulmonary TB, and 9/13 (69%) were smear positive. One patient (7%) had HIV coinfection, 5 (36%) had diabetes mellitus, and 5/14 (36%) had previous treatment TB. All patients were non-US-born and 5/14 (36%) had private insurance. All patients achieved sputum culture conversion within a mean of 71 days (26-116); 5 after starting bedaquiline. Twelve (86%) completed treatment and 1 (7%) moved out of the country. One patient (7%) had QTc prolongation >500 milliseconds and died 20 months after discontinuing bedaquiline of a cause not attributable to the drug. Common adverse events were peripheral neuropathy 7/14 (50%), not customarily associated with bedaquiline use, and QTc prolongation 6/14 (43%)., Conclusions: Of 14 patients, 1 (7%) had an adverse event necessitating bedaquiline discontinuation. Safety, culture conversion, and treatment completion in this series (7%) support use of bedaquiline for the treatment of MDR/XDR TB., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB. Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided. Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.

Background: Tuberculosis (TB) Regional Training and Medical Consultation Centers (RTMCCs) were established in 2005 for TB medical consultation, training and education in the United States. A medical consultation database (MCD) captured all consultations provided by RTMCCs; we report on those provided from June 1, 2010 to May 31, 2014., Methods: All MCD consultations during 2010-2014 were categorized into: provider type, setting, consultation topic, and patient age. We analyzed data frequencies and performed subgroup analyses by RTMCC, by TB incidence for the geographical area, and by year of consultation. End-user satisfaction was assessed by a 2016 telephone evaluation of RTMCC services., Results: A total of 11,074 consultations were delivered, with 10,754 (97.1%) in the U.S. and its current or former territories. Of these, 6018 (56%) were for high, 2443 (22.7%) for medium, and 2293 (21.3%) for low TB incidence settings. Most were for adults (81.3%) and answered within 24 h (96.2%). Nearly 2/3 consultations originated from health departments; providers included mostly physicians (44.3%) or nurses (37.6%). Common consult categories included TB disease (47.7%), case management (29.8%), latent TB infection (19.3%), diagnosis (16.1%), pharmacology (14.7%) and adverse side effects (14.3%). Among adverse side effects, hepatotoxicity was most common (39.6%). Volume and nature of consult requests remained relatively stable over the four-year period. Feedback from a 2016 CDC evaluation indicated overall satisfaction with RTMCC medical consultation services., Conclusion: RTMCCS were an important source of TB medical consultation over the time-frame of this assessment and provided quality expert consultation within 24 h. RMTCCs represent a reservoir of TB subject-matter expertise in the United States., (© 2019 Published by Elsevier Ltd.)

Background: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis., Methods: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration., Findings: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I 2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses., Interpretation: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition., Funding: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We describe 2 young, female patients who developed drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome while on treatment for pulmonary tuberculosis (TB). Active TB was treated successfully with second-line TB medications, including moxifloxacin, ethambutol, linezolid, and amikacin for 18 months.

Affecting both mother and the existing pregnancy, tuberculosis (TB) increases the likelihood of poor birth outcomes. Despite substantial clinical need for TB prevention and treatment, pregnant women remain neglected by research initiatives. As members of 3 community advisory boards that provide input into TB drug trials, we offer a community perspective on the inclusion of pregnant women in TB drug research and discuss (1) our perspective on the risk/benefit tradeoff of including pregnant women in research to address different forms of TB; (2) recent examples of progress in this area; (3) lessons learned from the human immunodeficiency virus research field, where pregnant women have enjoyed better-although imperfect-representation in research; and (4) recommendations for different stakeholders, including researchers, regulatory authorities, ethics committees, and policymakers., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey., Methods: Publications citing the 2008 research agenda and normative documents were reviewed for evidence gaps. Gaps were formulated into questions and grouped as in the 2008 research agenda: Laboratory Support, Treatment Strategy, Programmatically Relevant Research, Epidemiology, and Management of Contacts. A survey was distributed through snowball sampling to identify research priorities. Respondent priority rankings were scored and summarized by mean. Sensitivity analyses explored weighting and handling of missing rankings., Results: Thirty normative documents and publications were reviewed for stated research needs; these were collapsed into 56 research questions across 5 categories. Of more than 500 survey recipients, 133 ranked priorities within at least one category. Priorities within categories included new diagnostics and their effect on improving treatment outcomes, improved diagnosis of paucibacillary and extra pulmonary TB, and development of shorter, effective regimens. Interruption of nosocomial transmission and treatment for latent TB infection in contacts of known MDR-TB patients were also top priorities in their respective categories. Results were internally consistent and robust., Discussion: Priorities retained from the 2008 research agenda include shorter MDR-TB regimens and averting transmission. Limitations of recent advances were implied in the continued quest for: shorter regimens containing new drugs, rapid diagnostics that improve treatment outcomes, and improved methods of estimating burden without representative data., Conclusion: There is continuity around the priorities for research in PMDT. Coordinated efforts to address questions regarding shorter treatment regimens, knowledge of disease burden without representative data, and treatment for LTBI in contacts of known DR-TB patients are essential to stem the epidemic of TB, including DR-TB.

Objective: A population-based study of 135 multidrug-resistant tuberculosis (MDR-TB) patients reported to the Centers for Disease Control and Prevention (CDC) during 2005-2007 found 73% were hospitalized. We analyzed factors associated with hospitalization., Methods: We assessed statistically significant multivariable associations with US in-patient TB diagnosis, frequency of hospitalization, length of hospital stay, and in-patient direct costs to the health care system., Results: Of 98 hospitalized patients, 83 (85%) were foreign-born. Blacks, diabetics, or smokers were more likely, and patients with disseminated disease less likely, to receive their TB diagnosis while hospitalized. Patients aged ⩾65 years, those with the acquired immune-deficiency syndrome (AIDS), or with private insurance, were hospitalized more frequently. Excluding deaths, length of stay was greater for patients aged ⩾65 years, those with extensively drug-resistant TB (XDR-TB), those residing in Texas, those with AIDS, those who were unemployed, or those who had TB resistant to all first-line medications vs. others. Average hospitalization cost per XDR-TB patient (US$285 000) was 3.5 times that per MDR-TB patient (US$81 000), in 2010 dollars. Hospitalization episode costs for MDR-TB rank third highest and those for XDR-TB highest among the principal diagnoses., Conclusions: Hospitalization was common and remains a critical care component for patients who were older, had comorbidities, or required complex management due to XDR-TB. MDR-TB in-patient costs are among the highest for any disease.

Rifampicin is a widely used anti-tuberculosis agent. On rare occasions, the drug can cause adverse effects such as acute renal failure, though most regain complete renal function upon discontinuation of therapy. The following case report describes a 38 year old Hispanic male presenting with pulmonary tuberculosis who developed rifampicin-induced renal toxicity. He recovered renal function upon discontinuation of the medication without the use of corticosteroids., (© 2015 The Authors.)

Multidrug-resistant tuberculosis (MDR-TB) is on the rise, and is difficult to treat. The approval of two new drugs, bedaquiline and delamanid, and growing evidence for the use of linezolid, offer renewed hope for addressing MDR-TB. However, access to these medicines remains a significant challenge. These drugs have not been registered for TB in most settings; barriers to preapproval access persist; and high pricing and intellectual property restrictions limit access. Many unanswered research questions about optimal use of these drugs also limit access, particularly for vulnerable populations. This review outlines challenges in accessing drugs encountered from the perspective of clinicians, patients and affected communities, and offers potential solutions., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To describe factors associated with multidrug-resistant (MDR), including extensively-drug-resistant (XDR), tuberculosis (TB) in the United States, we abstracted inpatient, laboratory, and public health clinic records of a sample of MDR TB patients reported to the Centers for Disease Control and Prevention from California, New York City, and Texas during 2005-2007. At initial diagnosis, MDR TB was detected in 94% of 130 MDR TB patients and XDR TB in 80% of 5 XDR TB patients. Mutually exclusive resistance was 4% XDR, 17% pre-XDR, 24% total first-line resistance, 43% isoniazid/rifampin/rifabutin-plus-other resistance, and 13% isoniazid/rifampin/rifabutin-only resistance. Nearly three-quarters of patients were hospitalized, 78% completed treatment, and 9% died during treatment. Direct costs, mostly covered by the public sector, averaged $134,000 per MDR TB and $430,000 per XDR TB patient; in comparison, estimated cost per non-MDR TB patient is $17,000. Drug resistance was extensive, care was complex, treatment completion rates were high, and treatment was expensive.

From January 1986 through December 1993, we operated on 59 patients with documented Mycobacterium tuberculosis infection. Indications for operation were as follows: multidrug-resistant tuberculosis (MDRTB) in 19 patients; bronchopleural fistula secondary to Mycobacterium tuberculosis infection in 12; massive hemoptysis in 5; destroyed lung in 7; solitary nodule in 7; trapped lung in 3; complicated cavity in 4; and empyema in 2. Sixty-five operative procedures were performed: pneumonectomy with latissimus muscle flap in 15 patients; pneumonectomy in 3; lobectomy in 16; segmental or wedge resection in 11; decortication in 5; window thoracostomy in 3; thoracoplasty with myoplasty in 4; tube thoracostomy in 4; return to operating room for bleeding in 2; Clagett procedure in 1; and drainage of a cold abscess in 1. There were no operative deaths. Major postoperative complications occurred in 5 patients. The two late deaths were in patients with MDRTB: 1 with progressive disease and massive hemoptysis and the other with a relapse of MDRTB. Of the patients operated on as part of their therapeutic regimen for MDRTB, 17 (89%) of 19 have remained culture negative. We conclude that (1) surgery still plays an important role in the management of patients with Mycobacterium tuberculosis infection; (2) surgical intervention can be performed with acceptable mortality and morbidity; (3) a variety of procedures are needed to effect cure; and (4) encouraging results in patients with MDRTB support surgical therapy in this difficult group of patients.

Pulmonary tuberculosis is found predominantly in the lung apices. In diabetics it has been suggested that tuberculosis tended to occur predominantly in the lower lobes. A retrospective chart review was performed of all patients with a diagnosis of diabetes and pulmonary tuberculosis admitted to a health care facility to determine the presenting chest roentgenographic location of tuberculosis. Multiple lobe involvement was the predominant chest roentgenographic finding in both diabetics and nondiabetics with pulmonary tuberculosis. Since tuberculosis and diabetes frequently coexist in the population at risk for tuberculosis, clinicians should suspect tuberculosis in the diabetic with an abnormality on chest roentgenogram. Aggressive diagnostic measures and specific chemotherapy should be given and monitored to treat pulmonary tuberculosis.

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) are potent immunomodulatory cytokines which are produced principally by cells of the macrophage-monocyte lineage. We conducted an investigation to assess the secretion of these cytokines by bronchoalveolar macrophages from patients with progressive stages of human immunodeficiency virus (HIV-1) infection. The mean level of TNF-alpha produced by macrophages from 9 patients with AIDS was significantly reduced compared with the responses of macrophages from 6 healthy HIV-1-seronegative persons, 6 patients with either asymptomatic HIV-1 infection or persistent generalized lymphadenopathy, and 6 patients with AIDS-related complex (ARC). The four study groups did not differ in their mean IL-1 beta responses. However, within the HIV-1-infected patient population, macrophages from 4 patients, 3 of whom had AIDS and 1 with ARC, failed to secrete detectable levels of IL-1 beta. All 4 patients were also nonresponsive in assays for TNF-alpha. These data establish that advanced HIV-1 infection may result in a pronounced dysfunction in the cytokine responses of alveolar macrophages.

This paper examines the hypothesis that latent murine cytomegalovirus (MCMV) may be transmitted in kidney tissue to transplant recipients. Balb/c mice were infected with MCMV, and at intervals of less than 1 week to greater than 1 year, transmission of the virus from infected donors was attempted by transplantation of kidney sections or transfusion of blood into uninfected recipients. Graft recipients were killed from 2-4 weeks later, and cultured for MCMV. Restriction endonuclease digestion profiles of viral DNA were performed. Acutely infected donors transmitted MCMV in kidney tissue to 83-66% of untreated, susceptible recipients. Latently infected donors transmitted the infecting strain of virus to 20% of all and 31% of immunosuppressed recipients but to 37% of the syngeneic versus 21% of the allogeneic (P less than .027). Blood transfusions transmitted latent virus to 28% of recipients. In conclusion, kidney tissue may serve as the source of latent virus in this murine transplantation model. Retained blood in the kidney is unlikely to be the only source of virus.

A brain abscess caused by a new variety of Cladosporium trichoides occurred in a previously healthy man. A reversed T-suppressor/helper cell ratio was noted as the only immunologic abnormality. He required three surgical procedures, the last an occipital lobectomy, and antifungal chemotherapy to control his disease. He received 2,068 mg of amphotericin B and one year of flucytosine at 6 g per day. Ten months after the last surgery he is without evidence of disease. C. trichoides var. chlamydosporum was isolated from the abscess. It differed from C. trichoides by producing chlamydospores in vitro and only hyphae in the brain abscess. On modified Sabouraud agar, the fungus did not grow at 25 degrees C and grew poorly at 30 degrees C and 37 degrees C. Histologic sections revealed necrosis, no encapsulation, and no epitheliod cells.

A recurrence of cryptococcosis sixteen years after the primary infection as a penile ulcer is reported. The clinical manifestations of genitourinary and skin involvement by cryptococci are discussed. The epidemiology, pathogenesis, diagnosis, and treatment of penile mycotic infections are reviewed.

Infective endocarditis is an important but uncommon complication in obstetric or gynecologic practice; we found only 124 cases reported in English and selected European papers during the last 40 years. The majority of cases (74%) were caused by streptococci; viridans streptococci predominated, while enterococci and group B streptococci were uncommon except after abortion. The overall mortality rate was 29%, while the mortality rate for the fetus when the mother developed infective endocarditis was 23%. The incidence of endocarditis in this setting is low and seems to be decreasing. Therefore, the risk-benefit ratio may not favor routine use of prophylaxis for endocarditis. We conclude that antibiotics need not be given for prevention of endocarditis before most common obstetric and gynecologic procedures. These include uncomplicated vaginal deliveries, uncomplicated spontaneous or induced abortions, dilatation and curettage, insertion or removal of intrauterine contraceptive devices (in the absence of pelvic infection), and biopsies of the cervix. For patients in whom both the underlying heart lesion and the obstetric or gynecologic procedure seem to pose significant risk for endocarditis, prophylaxis should be given. Two parenteral regimens for patients at highest risk are recommended: ampicillin plus gentamicin or vancomycin plus gentamicin. For lower-risk situations, one oral regimen is suggested: amoxicillin.