Intra vesical Bacillus Calmette-Guérin (BCG) instillation therapy is a well-established treatment for superficial bladder cancer, though it can occasionally lead to rare systemic complications. We report the case of a man in his early 80s who developed acute onset dyspnoea after receiving BCG therapy. Clinical evaluation supported by pathology and multi-modal imaging including X-rays, CTs and PET scans led to a diagnosis of BCG-induced pneumonitis, a rare but serious complication. The exact underlying mechanism is still not fully understood and thus no standardized treatment protocol exists. Success has been reported in the literature with the use of anti-tuberculous drugs in combination with steroids. Our patient was successfully treated with anti-tuberculous medication only, for 4 months. This case highlights the importance of maintaining awareness for systemic BCG findings in patients undergoing intra vesical BCG instillations.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection following intravesical BCG instillation is a rare complication of therapy that is associated with significant morbidity and mortality. We conducted a multicenter retrospective review of microbiologically confirmed M.bovis BCG infections in Western Australia over 22 years. Thirty-three patients were included in our study. All patients were male with a median age of 72 years. Localized infections accounted for 22/33 cases while disseminated infections accounted for 11/33 cases. The majority (n = 21) of positive isolates were cultured from urine specimens, followed by tissue and blood. The median time between first BCG instillation and infection was 7.5 months (95% CI, 3.5-11.5). The median duration of antimycobacterial therapy for localized infections was 6 months (95% CI, 4.1-7.9) as compared with 9 months (95% CI, 7.9-10.1) for disseminated infections (P = .039). The attributed mortality was 14.3%. M.bovis BCG infections have diverse clinical presentations and clinicians must have a high index of suspicion when assessing patients with a history of intravesical BCG instillation.

Intravesical administration of bacillus Calmette-Guérin is standard adjuvant treatment of non-muscle invasive bladder cancer. In spite of the fact that this immunotherapy is locoregional, there are still risk of some complications.

We describe two cases of systemic BCG infection after intravesical administration of BCG vaccine in patients with early stage of bladder cancer.

Both patients suffered from systemic BCG infection manifesting as BCG pneumonitis. After standard therapy with antituberculotic agents, both of them fully recovered.

BCG infection can occur as a rare but potentially serious complication of this treatment procedure. Gravity of this side effect and its specific therapy require prompt and right diagnosis.

Intravesical Bacillus Calmette-Guérin (BCG) instillation is a mainstay of adjunctive therapy for superficial bladder cancer that increases length of disease progression-free survival. Although usually well tolerated, moderate to severe local and systemic infectious complications can occur with this immunotherapy. Diagnosis is difficult and often based on high clinical suspicion since in many cases Mycobacterium bovis is not isolated. Treatment is not fully standardized but the combination of anti-tuberculosis drugs and corticosteroids is advocated in severe cases. The authors present an unusual case of a severe infectious complication following intravesical BCG instillation with pulmonary and kidney involvement. Prompt anti-tuberculosis treatment associated to corticosteroid resulted in a marked clinical and radiological improvement, supporting the diagnosis of disseminated BCG infection. Based on this, the authors aimed to review the literature on this exceptional complication of this immunotherapy.

We present the case of a patient with sepsis following a traumatic intra-bladder instillation of Calmette-Guerin Bacillus with pneumonia and possibly hepatitis. These complications are rare and could be induced by both immuno-allergic reaction and bacteremia. There is no specific guideline to treat this condition, but many clinicians depicting similar cases seem to agree on prolonged anti-tuberculous antibiotics with associated corticosteroid therapy. Following this therapy, the prognosis is generally favorable depending upon the fact that diagnosis has correctly been made. Our case highlights the fact that correct diagnosis has to be made especially in the presence of sepsis without a clear septic source.

Since its discovery by Theobald Smith, Mycobacterium bovis has been a human pathogen closely related to animal disease. At present, M. bovis tuberculosis is still a problem of importance in many countries and is considered the main cause of zoonotic tuberculosis throughout the world. Recent development of molecular epidemiological tools has helped us to improve our knowledge about transmission patterns of this organism, which causes a disease indistinguishable from that caused by Mycobacterium tuberculosis. Diagnosis and treatment of this mycobacterium are similar to those for conventional tuberculosis, with the important exceptions of constitutive resistance to pyrazinamide and the fact that multidrug-resistant and extremely drug-resistant M. bovis strains have been described. Among other members of this complex, Mycobacterium africanum is the cause of many cases of tuberculosis in West Africa and can be found in other areas mainly in association with immigration. M. bovis BCG is the currently available vaccine for tuberculosis, but it can cause disease in some patients. Other members of the M. tuberculosis complex are mainly animal pathogens with only exceptional cases of human disease, and there are even some strains, like "Mycobacterium canettii," which is a rare human pathogen that could have an important role in the knowledge of the evolution of tuberculosis in the history.

Fever of unknown origin (FUO) is defined as prolonged fever of >101 °F for at least 3 weeks that remains undiagnosed after a focused inpatient or outpatient workup. One of the most elusive FUO diagnoses is miliary tuberculosis (TB) which typically has few/no localizing signs/symptoms. Since the introduction of intravesicular Bacille Calmette-Guerin (BCG) treatment for bladder carcinoma, miliary BCG has only rarely been reported as a cause of FUO. As with miliary TB, there are few/no clues to suspect miliary BCG. We present an interesting case of FUO due to miliary BCG without any localizing signs, i.e., no lung, liver or prostate involvement. The only clues to the diagnosis of this FUO due to disseminated BCG were morning temperature spikes and otherwise unexplained highly elevated ferritin levels.

Immunotherapy with intravesical bacillus Calmette-Guérin (BCG) is considered the most effective adjuvant to endoscopic resection of bladder urothelial carcinoma in the therapeutic management of non-muscle invasive (NMIBC) at intermediate and high risk of recurrence and progression (pTa - pT1 and high-grade carcinoma in situ, CIS). Despite its proven efficacy, this type of treatment can determine local and systemic side effects of moderate or severe gravity, with the histological diagnosis of epithelioid granulomas in different organs, even in the absence of microbiological positivity of BCG. The immunotherapy with BCG is usually well tolerated and the virulence of the attenuated BCG is very low in immuno-competent patients, although only 16% of patients are able to receive all the instillations of the maintenance period (3 years) of treatment provided by the protocols, precisely because of side effects. Minor side effects usually resolve within a few hours or days. They develop in 3-5% of patients and usually consist of local infectious complications. Manifestations of BCG dissemination, such as vascular and ocular complications, are much less common, while BCG-disseminated infections, with granulomatous pneumonia or hepatitis present, are quite rare, representing 0.5-2% of the complications recorded. We present the clinical case of granulomatous lung and possibly liver infection caused by BCG in a patient aged 56 years being treated for several weeks with intravesical BCG for NIMBC pT1 high grade associated with CIS.

Intravesical bacillus Calmette-Guerin (BCG) therapy is an effective and widely used treatment for superficial bladder carcinoma. Local complications are frequent whereas systemic complications are rare but can be serious, and their management is not well known.

We describe retrospectively the records of 22 patients treated in 3 infectious disease departments, for complications related to intravesical BCG therapy as treatment of bladder cancer.

All the patients were male, with a median age of 68 years (range 56-88). Complications occurred after a median of 5 instillations (range 1-11) and were observed within 24 h following BCG instillation for 14 patients. Common symptoms were fever (n = 20), impaired general condition (n = 14), and shortness of breath (n = 7). Six patients had a systemic septic reaction leading to transfer into the intensive care unit for five of them. Lung infiltration was the most frequent presentation (n = 11). Mycobacterium bovis was isolated from only two patients, but histology showed the presence of a granuloma in nine patients. Antimycobacterial treatment was initialized in 17 patients; the outcome was favorable in 16 patients, with a median length of symptoms resolution of 22.5 days (range 5-425 days). Eleven patients received corticosteroids in addition to specific treatment and had a more rapid improvement. One patient died with disseminated BCGitis proved by biopsy.

Complications following intravesical BCG therapy are rare but can be severe and fatal. Histology seems to be the method that contributes most in confirmation of the diagnosis. Antimycobacterial therapy is effective, and probably more efficient when combined with corticosteroids, but the regimen and duration of the treatment are not standardized.

Intravesical instillation of Bacillus Calmette-Guérin (BCG) is a mainstay of adjunctive therapy for superficial bladder cancer. Disseminated BCG infection ("BCG-osis") after this therapy is rare and potentially life-threatening; only isolated case reports detail the histopathologic findings thereof, few of which had a diagnosis confirmed by molecular testing. We report 3 additional cases of BCG-osis complicating BCG therapy, all confirmed by cultures and molecular assays, including the first cases of wedge biopsy-confirmed BCG pneumonia and BCG olecranon bursitis. When suggested by a relevant clinical history, recognition of randomly distributed granulomas in any organ should prompt consideration of BCG-osis and liberal performance of AFB stains, aided by targeted molecular assays. Physicians should maintain a high index of suspicion when miliary infiltrates arise after intravesical BCG instillation, and close multidisciplinary communication is essential. Pathologist awareness of this rare cause of granulomatous inflammation aids recognition of BCG-osis and facilitates prompt initiation of antimycobacterial therapy.

Bacillus Calmette-Guérin (BCG) is the most effective intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG-related infectious complications may occur following instillation. Much of the current knowledge about this complication comes from single case reports, with heterogeneous diagnostic and therapeutic approaches and no investigation on risk factors for its occurrence. We retrospectively analyzed 256 patients treated with intravesical BCG in our institution during a 6-year period, with a minimum follow-up of 6 months after the last instillation. We also conducted a comprehensive review and pooled analysis of additional cases reported in the literature since 1975. Eleven patients (4.3%) developed systemic BCG infection in our institution, with miliary tuberculosis as the most common form (6 cases). A 3-drug antituberculosis regimen was initiated in all but 1 patient, with a favorable outcome in 9/10 cases. There were no significant differences in the mean number of transurethral resections prior to the first instillation, the time interval between both procedures, the overall mean number of instillations, or the presence of underlying immunosuppression between patients with or without BCG infection. We included 282 patients in the pooled analysis (271 from the literature and 11 from our institution). Disseminated (34.4%), genitourinary (23.4%), and osteomuscular (19.9%) infections were the most common presentations of disease. Specimens for microbiologic diagnosis were obtained in 87.2% of cases, and the diagnostic performances for acid-fast staining, conventional culture, and polymerase chain reaction (PCR)-based assays were 25.3%, 40.9%, and 41.8%, respectively. Most patients (82.5%) received antituberculosis therapy for a median of 6.0 (interquartile range: 4.0-9.0) months. Patients with disseminated infection more commonly received antituberculosis therapy and adjuvant corticosteroids, whereas those with reactive arthritis were frequently treated only with nonsteroidal antiinflammatory drugs (p < 0.001 for all comparisons). Attributable mortality was higher for patients aged ≥65 years (7.4% vs 2.1%; p = 0.091) and those with disseminated infection (9.9% vs 3.0%; p = 0.040) and vascular involvement (16.7% vs 4.6%; p = 0.064). The scheduled BCG regimen was resumed in only 2 of 36 patients with available data (5.6%), with an uneventful outcome. In the absence of an apparent predictor of the development of disseminated BCG infection after intravesical therapy, and considering the protean variety of clinical manifestations, it is essential to keep a high index of suspicion to initiate adequate therapy promptly and to evaluate carefully the risk-benefit balance of resuming intravesical BCG immunotherapy.

The authors present an unusual case of a 51-year-old man who developed relatively mild non-specific symptoms following intravesical BCG instillation for superficial transitional cell carcinoma of the bladder, with radiological investigations demonstrating typical features of miliary tuberculosis (TB). Transbronchial biopsy showed small foci of poorly formed granuloma suggestive of Mycobacterium infection. The patient's respiratory symptoms only became apparent 7 days after discharge having had 4 weeks of unremarkable inpatient stay where he remained clinically well. Prompt anti-TB treatment resulted in a remarkable improvement in his symptoms and radiological appearance, supporting the diagnosis of disseminated Mycobacterium bovis infection. This case highlights the importance of recognising miliary M bovis as a potential complication in patients receiving BCG immunotherapy, and that the disease course can be subclinical with delayed onset of symptoms.

A 78-year-old man was diagnosed with bladder carcinoma in situ and was successfully treated with intravesical bacillus Calmette-Guérin (BCG) instillations. At 6 months after the last dose, he developed fever, weight loss and malaise. He had an extensive negative workup at an outside hospital and was treated empirically with ciprofloxacin for 2 weeks. The fever resolved but returned months later and he was readmitted with pancytopenia, elevated alkaline phosphatase and ground glass opacities on the chest CT. Bone marrow and liver biopsies showed non-caseating granulomas and were negative for acid-fast bacillus (AFB) and fungal stains. Mycobacterium tuberculosis complex PCR of the bone marrow was negative. Owing to the high clinical suspicion of disseminated BCG infection, the patient was treated empirically. After 9 weeks of incubation, the bone marrow AFB culture grew Mycobacterium bovis. Within 2 months of treatment his symptoms resolved and his laboratory results normalised.

Miliary tuberculosis after intravesical Calmette-Guerin bacilli (BCG) therapy is rare. To date, only 23 cases have been reported. We describe the case of a patient on hemodialysis, review the literature, and call attention to the potential hazard of intravesical BCG therapy in patients on renal replacement therapy and the value of polymerase chain reaction-based methods for early diagnosis of this serious complication.

To report a case of multiple additional procedures after successful endovascular treatment of abdominal aortic aneurysm.

An endovascular abdominal aortic aneurysm repair with a bifurcated aortic Vanguard endograft successfully performed in 1999 resulted in multiple complications, including endoleaks and a row separation, treated endovascularly. Subsequently, tuberculosis sepsis and prosthesis infection resulted in long-term antibiotic treatment. Additional graft leaks, aneurysm sack growth, and sack ruptures were also treated endovascularly because the patient consistently denied open repair. Endovascular procedures, however, did not solve the problem, turning to be increasingly challenging. The patient finally approved open graft removal and aortobifemoral reconstruction that were successfully performed 11 years after the initial endograft implantation.

The patient has recovered from surgery well and is asymptomatic. No evidence of bacterial colonization was found according to the specimen taken during the laparotomy.

Vanguard and other first-generation aortic endografts are associated with high incidence of complications and reinterventions. Open surgery is a method of choice in similar cases.

Bacillus Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis. Usually, systemic complications due to BCG vaccination are quite rare. However, since BCG is a live vaccine, there is still a possibility that it may cause an infection.

Hepatic granuloma was found incidentally in an asymptomatic 5-month-old infant who was found dead in his bed. The probable cause of death was asphyxia due to milk aspiration into the lungs. The granuloma was composed of epithelioid histiocytes with frequent multinucleated Langhans-type giant cells and a small number of lymphocytes.

The cause of the asymptomatic granuloma was not identified, but was considered likely due to BCG vaccination.

Intravesical chemotherapy with bacilli Calmette-Guerin (BCG) has been an established therapy for preventing recurrence of, and for treatment of, superficial transitional cell carcinoma of the bladder, but it is not without side effects. A variety of renal complications have been reported and attributed to mycobacterial infection. Although renal complications are uncommon, several cases of interstitial nephritis (with or without granulomas) and mesangial glomerulonephritis have been reported. We report a 76-year-old male patient who developed acute renal failure due to interstitial nephritis after intravesical instillation of BCG. Corticosteroids may serve the recovery of renal function without concomitant use of anti-tubercular therapy, provided systemic signs and mycobacterial infection are absent. Serum creatinine should be checked in at-risk patients in order to detect this complication early.

Tuberculosis miliar is a very rare complication of bacillus Calmette-Guérin (BCG) immunotherapy that is associated to high mortality. Thus, early diagnosis and treatment is essential. At present, there is a polymerase chain reaction technique (PCR) which is a rapid diagnostic method with elevated sensitivity. Treatment with tuberculostatic agents should be initiated as soon as possible, the combination of corticosteroids and cycloserine in serious cases being advisable. A case of a 75 year old patient with intravesical BCG instillations after a transurethral resection of bladder cancer is presented. He was admitted to the Intensive Care Unit (ICU) due to severe acute respiratory failure evolving to acute respiratory distress syndrome (ARDS). Mycobacterium bovis DNA was identified by PCR in blood samples and bronchoaspirate (BAS). He was treated with tuberculostatic agents and corticosteroids, dying due to respiratory failure.

Local Bacillus Calmette-Guérin (BCG) immunotherapy is an effective and widely used treatment for superficial bladder carcinoma. Local side effects are frequent, whereas systemic side effects are rare, but more serious. Systemic BCG infection as a life-threatening complication of intravesical BCG instillation should be suspected in any patient who presents with persistent fever after BCG instillation for bladder cancer. A 62-year-old patient had been treated with 6 intravesical BCG instillations for recurrent, multifocal bladder carcinoma. 4 weeks after the last instillation, he presented with fever, malaise and scleral icterus. Laboratory tests revealed abnormal liver function tests, panzytopenia and signs of coagulation disorder. Bone marrow biopsy and liver biopsy showed noncaseating granulomas. Systemic BCG infection was suspected and antituberculous therapy combined with steroids was started. The patient developed severe sepsis and suffered from multiple organ failure. Despite partial improvement, the course was complicated by intracranial sinus thrombosis, and the patient died two month after admission.

The goal of this study was to apply temperature-mediated heteroduplex analysis using denaturing high-performance liquid chromatography to identify pyrazinamide (PZA) resistance in Mycobacterium tuberculosis isolates and simultaneously differentiate between M. tuberculosis and Mycobacterium bovis. Features that contributed to an optimal assay included the use of two different reference probes for the pncA gene targets from wild-type M. tuberculosis and wild-type M. bovis, optimization of the column temperature, increasing the starting concentration of the elution buffer, and reducing the rate of elution buffer increase (slope). A total of 69 strains were studied, including 48 wild-type M. tuberculosis strains (13 were PZA-resistant strains) and 21 M. bovis strains (8 were BCG strains). In all isolates tested, wild-type M. tuberculosis generated a single-peak pattern when mixed with the M. tuberculosis probe and a double-peak pattern with the M. bovis probe. In contrast, all M. bovis isolates generated a double-peak pattern when mixed with the M. tuberculosis probe and a single-peak pattern with the M. bovis probe. PZA-resistant mutant M. tuberculosis isolates generated characteristic patterns that were easily distinguishable from both wild-type M. tuberculosis and M. bovis isolates. Chromatographic patterns generated by the two reference probes allowed the rapid detection of PZA resistance with the simultaneous ability to distinguish between M. tuberculosis and M. bovis. This approach may allow the detection of drug resistance-associated mutations, with potential application to clinical and epidemiological aspects of tuberculosis control.

Intravesical instillation of bacille Calmette-Guérin (BCG) effectively treats transitional cell carcinoma of the bladder. Occasionally, BCG infection complicates such treatment. In some patients, infection appears early (within 3 months after instillation) and is characterized by generalized symptoms, with pneumonitis and hepatitis. Late-presentation disease occurs >1 year after the first BCG treatment and usually involves focal infection of the genitourinary tract (the site at which bacteria were introduced) and/or other sites that are typical for reactivation of mycobacterial disease, such as the vertebral spine or the retroperitoneal tissues. Noncaseating granulomas are found in the majority of cases, whether early or late. Most patients respond to treatment with antituberculous drugs; in early-presentation disease, when features of hypersensitivity predominate, glucocorticosteroids are sometimes added. Late localized infection often requires surgical resection.

We report a culture-proven case of Mycobacterium bovis vertebral osteomyelitis in a 76-year-old man who had undergone intravesical BCG therapy for bladder cancer 7 years previously. He presented with debilitating back pain and had radiographic evidence of T6-7 disk space destruction with involvement of adjacent vertebrae. Tissue culture from the disk space confirmed the diagnosis of vertebral osteomyelitis due to hematogenous spread of M. bovis. Treatment with antituberculous medications was begun soon after tissue diagnosis was made, and the patient fared well with medical therapy alone. Although uncommon, this infectious complication of BCG therapy should always be considered in the appropriate clinical setting. Timely diagnosis is important, because chemotherapy, when initiated early in the disease, can preclude the necessity for surgical intervention.

Bladder instillations with Bacillus Calmette-Guerin (BCG) are commonly used as immunotherapy for bladder carcinoma. Sometimes patients experience serious systemic side effects, such as sepsis or pneumonitis. Granulomatous hepatitis is a rare serious side effect, which has been considered a hypersensitivity reaction to BCG.

The first case of granulomatous hepatitis after BCG bladder instillation in which mycobacteria were identified by staining techniques and mycobacterial DNA was detected in liver tissue using the polymerase chain reaction is reported.

The granulomatous hepatitis was caused by BCG infection of the liver after haematogenous dissemination of BCG, rather than hypersensitivity.

Recent surveys in the USA show that many mycobacteriology laboratories continue to use less-than-optimum culture and susceptibility testing methods. This seems to be true for European countries as well. The past few years have brought significant changes to the clinical tuberculosis laboratory. High-performance liquid chromatography and direct detection of acid-fast bacilli in clinical specimens aim at the same goal: increased sensitivity and specificity of the diagnostic approach and reduction of turnaround time. This review outlines a brief comparison between contemporary traditional methods and the latest developments in the direct detection of acid-fast bacilli. If patient care and public health are always considered paramount, regardless of admission time, hospital type, etc., the current concept of services has several shortcomings. One way to manage this situation is to sort and allocate specimens according to a system of priorities. There is a growing realization that no single method by itself is the best. To streamline the best choice for laboratory diagnosis, an additional dynamic acid-fast network is presented: 'Point-of-Care,' 'Fast Track,' and 'Specialty' laboratories. The physician interacts with all three types of laboratories, so ongoing communication between the physician and the laboratory is essential. Laboratorians must work together in the formation of this dynamic acid-fast network to improve service rendered for our patients.