Clinical standards for the management of adverse effects during treatment for TB.

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

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.

Multidrug-resistant tuberculosis care in the United States.

BACKGROUND: To examine the utilization of the Tuberculosis (TB) Centers of Excellence (COE) medical consultation service and evaluate how these services were being employed for patients in relation to multidrug-resistant TB (MDR-TB).METHODS: Medical consults are documented in a secure database. The database was queried for MDR-TB consultations over the period 1 January 2013-31 December 2017. All were analyzed to assess provider type, center, setting, year of call, and type of patient (pediatric vs. adult). A subgroup was randomly selected for thematic analysis.RESULTS: The centers received 1560 MDR-TB consultation requests over this period. Providers requesting consults were primarily physicians (55%). The majority of requests were from public health departments (64%) and for adult patients (80%). Four major topic areas emerged: 1) initial management of MDR-TB, 2) MDR-TB longitudinal treatment and complications, 3) management of persons exposed to MDR-TB, and 4) MDR-TB treatment completion.CONCLUSIONS: Analysis of these consultations provides insight into the type of expert advice about MDR-TB that was provided. These findings highlight topics where increased medical training and education may help to improve MDR-TB-related practices.

Characteristics and costs of multidrug-resistant tuberculosis in-patient care in the United States, 2005-2007.

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.

Current role of surgery in Mycobacterium tuberculosis.

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 in diabetics.

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.

Varied presentations and responses to treatment of infections caused by Mycobacterium haemophilum in patients with AIDS.

We describe three patients with AIDS who developed clinically significant infection with Mycobacterium haemophilum. One patient had skin and bone involvement and suspected laryngeal involvement; the second had extensive abdominal adenopathy with partial bowel obstruction; and the third presented with limited skin involvement. Each patient responded transiently to antimycobacterial therapy, but disease recurred and progressed in all three cases. Recovery of M. haemophilum requires a high level of clinical suspicion and special handling of mycobacterial cultures by the microbiology laboratory, including cultivation on enriched chocolate agar or heme-supplemented media and incubation at 30 degrees C for up to 8 weeks. Characteristic patterns of drug susceptibility for this organism have been only partially defined. Reported responses to antimycobacterial therapy in AIDS patients with M. haemophilum infection have been poor, and the optimal therapeutic regimen is not yet known. The prognosis for recovery appears to depend heavily on host-related factors, particularly the degree of immunosuppression.

Production of tumor necrosis factor-alpha and interleukin-1 by alveolar macrophages from HIV-1-infected persons.

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.

Hepatitis B vaccines in patients with chronic renal failure before dialysis.

Hepatitis B remains a significant risk to patients receiving chronic hemodialysis, but no certain method of prevention has been identified. We tested two vaccines, plasma-derived vaccine (40-micrograms dose) and recombinant-derived vaccine (40-micrograms and 20-micrograms doses), in 61 patients with chronic renal failure who were not yet dependent on dialysis. Patients were followed up clinically and with laboratory tests of kidney function and hepatitis B virus serology for one year. Significantly more recipients of plasma-derived vaccine responded to vaccination; they also achieved a higher titer of antibody to hepatitis B virus than did recipients of recombinant-derived vaccine when evaluated at 6, 7, 9, and 12 mo after vaccination. No serious side effects were observed with any vaccine preparation, nor were excessive adverse effects observed in any group. Compared with the dialysis patients previously studied, patients with renal failure who were not yet dependent on dialysis responded more favorably to the hepatitis B virus vaccine.

Infective endocarditis in obstetric and gynecologic practice.

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.

Pacemaker-associated sepsis: successful medical management.

We have presented a case of Staphylococcus aureus septicemia in a patient with a transvenous pacemaker who responded to conservative medical therapy.

Penile cryptococcosis with review of mycotic infections of penis.

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.

Transmission of latent cytomegalovirus in a murine kidney tissue transplantation model.

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.

Non-A, non-B hepatitis and chronic dialysis--another dilemma.

To define the incidence of non-A, non-B (NANB) hepatitis and evaluate possible risk factors, we reviewed records of 163 patients on chronic dialysis during a 3-year period. 23 cases of NANB hepatitis occurred, 13 (27%) in 49 center dialysis, 8 (10%) in 77 home hemodialysis (p less than 0.02) and 2 (5%) in 37 peritoneal dialysis patients (p less than 0.01). Hepatitis patients received significantly more transfusions than controls. Numbers of transfusions and of patients transfused were not significantly different in center patients compared to home and peritoneal. 8 NANB patients received no transfusions. NANB was the most common cause of hepatitis in our unit (68%). Although transfusions were a likely etiologic factor, to explain the increased risk in center dialysis patients, disease in patients not transfused and development of NANB hepatitis without a known parenteral exposure in a physician assigned to the Nephrology Service, we feel another etiologic factor was important, the dialysis center.

Brain abscess caused by a variety of cladosporium trichoides.

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.

Urine cortisol/creatinine ratio in controlled insulin-induced hypoglycemia.

An elevated urine cortisol/creatinine ratio has been presented as a simple laboratory method to detect nocturnal hypoglycemia. The present study examines the time course of the rise and fall of the urine cortisol/creatinine ratio in 11 patients following insulin-induced hypoglycemia. The mean urine cortisol/creatinine ratios at 1 and 3 h after the onset of symptomatic hypoglycemia were 170 +/- 103 and 62 +/- 23, respectively. These were significantly greater (P less than 0.01) than the basal ratio of 13 +/- 7. By 5 h, the ratio had fallen to 19 +/- 11, which was similar to basal values. The study documents the sensitivity of the urine cortisol/creatinine ratio in detecting hypoglycemia but indicates that after 3 h, the ratio may return to normal despite a previous hypoglycemic episode.