18 F-FDG PET/CT influences management in patients with known or suspected pancreatic cancer.

BACKGROUND: The aims of this study were (i) to assess and validate the incremental information of positron emission tomography/computed tomography (PET/CT) over conventional staging investigations (CSI) and (ii) to assess the management impact of PET/CT in patients with known or suspected pancreatic cancer. METHODS: Between October 2007 and September 2008, 22 PET/CT scans were performed using a dedicated PET/CT scanner in 21 patients with known or suspected pancreatic cancer. Follow up was used to reconcile discordance between PET/CT and CSI. The pre-PET/CT management plan and/or intent were prospectively recorded in all scans. The post-PET/CT management plan was determined from the medical record and/or discussions with treating clinicians. The management impact of PET/CT was classified as high, medium, low or none defined using Australian and New Zealand Association of Physicians in Nuclear Medicine PET data collection project criteria. RESULTS: PET/CT and CSI were discordant in 14/22 (64%: 95% CI; 43-84%) scans. Of the 14 discordant scans, PET/CT assessment was correct in eight, conventional imaging in four and there was insufficient information in two. Overall, PET/CT management impact was classified as high (n= 6), medium (n= 3), low (n= 9) or none (n= 4). Significant changes in management (high or medium impact) were induced by PET/CT in 9/22 scans (41%: 95% CI; 20-62%) predominantly by correctly modifying the disease extent. CONCLUSION: PET/CT has an incremental benefit over CSI and has a significant impact on management in patients with known or suspected pancreatic cancer. PET/CT merits consideration as part of the non-invasive evaluation of patients with known or suspected pancreatic cancer.

The international epidemiology of disseminated Mycobacterium avium complex infection in AIDS. International MAC Study Group.

OBJECTIVE: To determine rates of disseminated Mycobacterium avium complex (MAC) infection among AIDS patients in developed and developing countries, and to determine whether different rates reflect differences in exposure or immunity, or both. DESIGN: Prospective cohort study. SETTING: University hospitals and outpatient AIDS programs. METHODS: HIV-infected subjects with CD4 counts < 200 x 10(6)/l were interviewed and had CD4 lymphocyte counts, blood cultures for mycobacteria (baseline and at 6 months), and skin tests with purified protein derivative (PPD) and M. avium sensitin. RESULTS: Among 566 study patients rates of disseminated MAC were 10.5-21.6% in New Hampshire, Boston and Finland compared to 2.4-2.6% in Trinidad and Kenya (P < 0.001). PPD skin test reactions > or = 5 mm were present in 20% of patients from Kenya compared to 1% at other sites (P < 0.001). Among patients from the United States and Finland, multiple logistic regression indicated that occupational exposure to soil and water was associated with a decreased risk of disseminated MAC, whereas the following were associated with an increased risk of disseminated MAC: low CD4 count, swimming in an indoor pool, history of bronchoscopy, regular consumption of raw or partially cooked fish/shellfish and treatment with granulocyte colony-stimulating factor. CONCLUSIONS: Rates of disseminated MAC in AIDS are higher in developed than developing countries and are due to both differences in exposure and differences in immunity. These data provide a rationale for prevention of MAC through both active immunization and reduction in exposure to the organism.

A phase II/III trial of antimicrobial therapy with or without amikacin in the treatment of disseminated Mycobacterium avium infection in HIV-infected individuals. AIDS Clinical Trials Group Protocol 135 Study Team.

OBJECTIVE: To determine the clinical and microbiologic benefit of adding amikacin to a four-drug oral regimen for treatment of disseminated Mycobacterium avium infection in HIV-infected patients. DESIGN: A randomized, open-labeled, comparative trial. SETTING: Outpatient clinics. PATIENTS: Seventy-four patients with HIV and symptomatic bacteremic M. avium infection. INTERVENTIONS: Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks. MAIN OUTCOME MEASURE: Clinical and microbiologic response at 4 weeks; quantitative level of bacteremia with M. avium. RESULTS: No difference in clinical response was noted with the addition of amikacin to the four-drug oral regimen, and only 25% in either group had a complete or partial response at 4 weeks. A comparable quantitative decrease in bacteremia was noted in both treatment groups, with 16% of patients being culture-negative at 4 weeks and 38% at 12 weeks. Toxicities were mainly gastrointestinal. Amikacin was well tolerated. Median survival was 30 weeks in both groups. CONCLUSIONS: The addition of amikacin to a four-drug oral regimen of rifampin, ciprofloxacin, clofazimine, and ethambutol did not provide clinical or microbiologic benefit.

Bacteremia due to Mycobacterium tuberculosis in patients with human immunodeficiency virus infection. A report of 9 cases and a review of the literature.

Mycobacterium tuberculosis bacteremia is being reported more frequently in patients with human immunodeficiency virus, type 1 (HIV-1) infection. We report 9 patients with bacteremia due to M. tuberculosis and HIV infection who were identified over a 36-month period. Of the 9 patients studied, 8 were male, 8 were black, 6 were born in Haiti, 3 were homeless, 2 were intravenous drug users, and 1 was homosexual. At the time of diagnosis, 3 patients had the acquired immunodeficiency syndrome (AIDS) and 5 patients had CD4 lymphocyte counts less than or equal to 170 cells/mm3, indicating marked immunodeficiency. All 9 patients presented with temperature greater than 38.3 degrees C, 5 (50%) had abnormal chest roentgenogram on admission, and each of the patients tested had elevations of at least 2 liver function tests. Eight patients (80%) had M. tuberculosis isolated from sputum or other body fluids and tissues. All blood isolates of M. tuberculosis were identified from Dupont Isolator tubes. Antibiotic-resistant isolates of M. tuberculosis were cultured from 3 of the 6 patients born in Haiti. One patient died before diagnosis and received no antimycobacterial therapy; 7 of the remaining 8 patients appeared to respond to treatment. Our data, and a review of the literature, suggest that bacteremia due to M. tuberculosis is becoming more frequent, and that blood cultures may be helpful in establishing or confirming a diagnosis of tuberculosis in patients with HIV-1 infection.

Preventing nosocomial pneumonia: state of the art and perspectives for the 1990s.

In the 1980s, nosocomial pneumonia became the second most common nosocomial infection in the United States. Gram-negative bacilli and Staphylococcus aureus were the most frequently isolated bacteria. Methods to improve the diagnostic sensitivity and specificity included transtracheal aspirates and bronchoscopy with protected specimen brush or bronchoalveolar lavage. Multivariate analysis was used to identify independent risk factors for pneumonia and fatality in different subsets of high-risk patients. Gastric pH and colonization were evaluated as risk factors for pneumonia in mechanically ventilated patients. Colonized respiratory therapy equipment and contaminated tubing condensate and in-line medication nebulizers were suggested as possible sources of nosocomial pathogens. Staff education programs, the use of barrier precautions, and selective decontamination of the digestive tract were associated with reduced rates of lower respiratory tract infection. Despite a decade of progress in our understanding of nosocomial pneumonia, progress in the 1990s will undoubtedly include molecular epidemiologic techniques, appropriate application of risk factor data, and the use of new methods for the diagnosis of pneumonia. Prevention strategies should focus on more effective infection control techniques, improved invasive devices/equipment, and the judicious use of antibiotics for treatment and prophylaxis.

Mycobacterium gordonae: a possible opportunistic respiratory tract pathogen in patients with advanced human immunodeficiency virus, type 1 infection.

STUDY OBJECTIVE: To determine if Mycobacterium gordonae is an opportunistic respiratory tract pathogen in patients infected with human immunodeficiency virus, type 1 (HIV-1). DESIGN: Retrospective review of medical records of all patients with positive cultures for M gordonae from 1987 to 1989. PATIENTS: Fifteen patients had positive sputum cultures for M gordonae: five patients had AIDS or had HIV-1 infections with less than or equal to 180 CD4 cells/cu mm, and ten patients had no clinical evidence of HIV-1 infection. RESULTS: Three of the five HIV-1 infected patients had clinical, roentgenographic, and microbiologic evidence of pulmonary infection due to M gordonae that responded to antimycobacterial therapy. One of the two remaining HIV-1 infected patients had disseminated M tuberculosis and possible coinfection with M gordonae, and the other was lost to follow-up. None of the ten patients without evidence of HIV-1 infection was considered to have M gordonae respiratory tract infection. CONCLUSIONS: Sputum isolates of M gordonae should be considered potential opportunistic respiratory tract pathogens in patients with advanced HIV-1 infection and with otherwise unexplained pulmonary infection.

The potential for induction peptide receptor chemoradionuclide therapy to render inoperable pancreatic and duodenal neuroendocrine tumours resectable.

AIMS: To assess the clinical utility of peptide receptor chemoradionuclide therapy (PRCRT) using (177)Lu-octreotate (LuTate) with concurrent 5FU chemotherapy in patients with inoperable primary pancreatic and duodenal neuroendocrine tumours (NETs). METHODS: Between December 2006 and October 2009, five patients with progressive inoperable pancreatic and duodenal NETs without distant metastatic disease or with a potentially resectable solitary distant metastasis were treated with PRCRT; in combination with external beam radiotherapy in one case. Patients were followed up three months post-treatment with somatostatin receptor scintigraphy, radiology, biochemical markers and clinical assessment. Radiological response classification was defined by Response Evaluation Criteria in Solid Tumours (RECIST) with the addition of a minor response (MR; 10-30% size reduction) classification. Long-term follow up was performed until July 2011. RESULTS: At three months post-treatment, all five patients had a scintigraphic response, four had a radiological response and three of the four symptomatic patients responded clinically. All five patients had an ongoing treatment response beyond three months including one where further tumour shrinkage facilitated curative surgery. All five patients are alive with 12-42 months of follow-up post-treatment. CONCLUSION: PRCRT can be effective in inoperable pancreatic and duodenal neuroendocrine tumours and may play a role as neoadjuvant therapy in this patient group.

Prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with AIDS: a cost-effectiveness analysis.

OBJECTIVE: To determine the effectiveness and costs of prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with AIDS. DESIGN: A decision analysis model was constructed to compare rifabutin (300 mg/day), azithromycin (1200 mg/week), and clarithromycin (500 mg twice per day) with no prophylaxis. Sensitivity analysis was done on all model parameters, including initial CD4 count for beginning prophylaxis. SETTING: The setting was hypothetical for the cost-effectiveness model. Clinical data were taken from published prospective randomized controlled trials. MAIN OUTCOME MEASURES: Outcomes were measured in terms of projected life expectancy, quality-adjusted life expectancy, direct medical costs, and cost-effectiveness in U.S. dollars per quality-adjusted life-year saved ($/QALY). RESULTS: For patients with AIDS and those having CD4 counts <75 cells/mm3, azithromycin, clarithromycin, and rifabutin prophylaxis increased lifetime per person MAC-related costs by $994, $2,117, and $2,185 U.S., respectively. Quality-adjusted life expectancy increased from 1.6068 QALYs to between 1.6186 and 1.6255 QALYs. The cost-effectiveness ratios were $58,200, $116,000, and $179,100/QALY saved for azithromycin, clarithromycin, and rifabutin prophylaxis, respectively, each compared with no prophylaxis. Results were most dependent on the annual cost of prophylaxis, the initial CD4 count when starting prophylaxis, and any survival benefit with prophylaxis. For each type of prophylaxis, strategies beginning with CD4 counts <25 or 50 cells/mm3 were substantially more cost-effective than those beginning in patients with higher CD4 counts. CONCLUSIONS: MAC prophylaxis is likely to cost society an additional $99 to $219 million U.S. per 100,000 patients treated. In the context of Centers for Disease Control and Prevention (CDC) recommendations to use prophylaxis in patients with CD4 counts <75 cells/mm3, azithromycin represents the best value and is most cost-effective when used in patients with CD4 counts <25 cells/mm3.

Nosocomial pneumonia in the 1990s: update of epidemiology and risk factors.

Hospital-acquired pneumonia is the second most common nosocomial infection in the United States. Aspiration appears to be the major route for the entry of microorganisms into the lower respiratory tract. Nosocomial pneumonia may be caused by bacteria, viruses and fungi. Aerobic gram-negative bacilli and Staphylococcus aureus are the most common etiologic agents, but infection is usually polymicrobial. Risk factors for nosocomial pneumonia include host variables, colonization with nosocomial pathogens, and impaired response of pulmonary defenses to the microbial challenge. Bacteria causing nosocomial pneumonia may be part of the patient's endogenous flora, originate from the hands of hospital personnel, or result from the use of invasive devices. The mechanically ventilated patient has multiple risk factors that contribute to the high rate of nosocomial pneumonia. An understanding of the epidemiology and risk factors for nosocomial pneumonia is fundamental for implementation of preventive strategies to reduce patient morbidity, mortality, and hospital costs.

Persistent colonisation of potable water as a source of Mycobacterium avium infection in AIDS.

The source of Mycobacterium avium infection in AIDS has not been identified and it is not known whether most patients with AIDS acquire the organism from recent infection or by reactivation of previous infection. As part of a prospective epidemiological study, we isolated multiple colonies of M avium from patients with AIDS and from potable water to which they had been exposed. All isolates were analysed with pulsed field gel electrophoresis (PFGE). As judged by PFGE, 29 (81%) of 36 patients were infected with one or more unique clinical strains of M avium. 7 patients (19%) were infected with three groups of common strains. Group 1 included 3 patients who lived in separate rural areas and had no common exposures apart from treatment at hospital A. The same strain was isolated repeatedly during 41 months from a recirculating hot water system at hospital A; residential water cultures were negative. Group 2 included 2 patients with no common exposures apart from treatment at hospital B; the same strain was isolated repeatedly over a period of 24 months from a recirculating hot water system at hospital B. Patients in groups 1 and 2 had numerous possible exposures to hospital hot water. Group 3 included 2 patients treated at the same methadone treatment facility. In an institution the hot water system may be persistently colonised with a particular strain of M avium. HIV-infected patients exposed to these water sources can develop disseminated M avium infection.

Genetic diversity among strains of Mycobacterium avium causing monoclonal and polyclonal bacteremia in patients with AIDS.

To define the genetic diversity among Mycobacterium avium isolates from human immunodeficiency virus-infected patients, specimens were cultured prospectively, and isolates obtained from 14 patients (4 with positive blood, stool, and sputum; 6 with positive blood and stool; 3 with positive blood only; and 1 with positive stool only) were studied. Both serotyping and ribotyping had limited ability to discriminate among isolates from different patients, whereas the distinctive restriction fragment profiles resolved by pulsed-field gel electrophoresis indicated that each patient was infected by a unique strain. Of the 13 bacteremic patients, 2 were bacteremic concurrently with 2 distinct strains. The fact that M. avium isolates from AIDS patients exhibit considerable genetic diversity supports the hypothesis that the infection is acquired from various environmental sources. Further, individual patients are not infrequently bacteremic with > 1 strain simultaneously, which may need to be considered in protocols for the diagnosis and management of M. avium disease.

Polyclonal infections due to Mycobacterium avium complex in patients with AIDS detected by pulsed-field gel electrophoresis of sequential clinical isolates.

Invasive infection with organisms of the Mycobacterium avium complex (MAC) is common among patients with advanced human immunodeficiency virus infection. In previous studies, we analyzed multiple individual colonies of MAC isolated from specimens obtained at the same time and observed that 14 to 20% of patients are simultaneously infected with more than one strain. In this study, we examined sequential isolates from 12 patients with AIDS who had two or more MAC isolates available from clinical specimens collected more than 1 week apart; the intervals between the first and last specimens ranged from 8 to 192 (median, 46) days. For each isolate, restriction digests of genomic DNA were analyzed by pulsed-field gel electrophoresis; DNA was prepared by using a protocol, described here in detail, which had been optimized for conditions of bacterial growth and lysis. The pulsed-field gel electrophoresis analysis identified four patients (33%) infected with two different MAC strains. Both M. avium and M. intracellulare were cultured from blood specimens from two patients. In each of the four patients, the second strain was identified from a culture taken within 14 days of the initial study isolate, and in three of these patients, the first strain was detected again in a subsequent culture. These observations suggest that the presence of two different strains among isolates from sequential cultures may reflect ongoing polyclonal infection. We conclude that polyclonal infection with MAC is common among patients with AIDS. The identification of such infections may be critical in the development of effective treatments.

Dual skin testing with Mycobacterium avium sensitin and purified protein derivative: an open study of patients with M. avium complex infection or tuberculosis.

The sensitivity and specificity of dual mycobacterial skin testing were assessed in an unblinded study of 22 patients with culture-confirmed Mycobacterium avium complex (MAC) infection and 20 patients with culture-confirmed Mycobacterium tuberculosis infection. Intradermal skin tests were performed with 0.1 mL of M. avium sensitin, 0.1 mL of PPD (purified protein derivative), and two control antigens (mumps and Candida). All patients with M. tuberculosis infection reacted to the skin tests; the mean reaction size was 19.7 +/- 1.4 mm when PPD was administered and 10.3 +/- 1.5 mm when M. avium sensitin was administered. Four patients with MAC were anergic; for the remaining 18, mean reactions of 15.2 +/- 1.4 mm to M. avium sensitin and 4.3 +/- 1.3 to PPD were noted. A skin test was defined as M. avium-dominant or PPD (M. tuberculosis)-dominant if there was a minimum reaction size of > or = 5 mm to the given species, and the reaction to the given species was > or = 3 mm greater than the reaction to the heterologous species. Dominant skin test reactions were present in 18 (90%) of 20 patients with M. tuberculosis and 15 (83%) of 18 nonanergic patients with MAC. The specificity of dominant skin tests was 100% for infection with M. tuberculosis and 100% for infection with MAC. M. avium-dominant skin tests identify subjects with prior MAC infection and distinguish them from patients with M. tuberculosis infection.

Evidence of previous infection with Mycobacterium avium-Mycobacterium intracellulare complex among healthy subjects: an international study of dominant mycobacterial skin test reactions.

Skin tests with 0.1 mL of intermediate-strength Mycobacterium tuberculosis purified protein derivative (PPD) and 0.1 mL of Mycobacterium avium sensitin were conducted on 484 healthy subjects from diverse geographic sites. Reactions of > or = 5 mm to one antigen that exceeded the reaction to the other by > or = 3 mm were considered M. avium- or PPD-dominant. PPD-dominant reactions were more frequent at sites where routine Bacille Calmette-Guérin immunization is done or where there are high rates of tuberculosis: New Hampshire, 2%; Boston, 7%; Finland, 14%; Trinidad, 26%; and Kenya, 28%. However, rates of M. avium-dominant reactions ranged from 7% to 12% at all sites. Analysis of dominant reactions based on a more stringent 10-mm minimum reaction size showed similar trends. These data suggest that exposure to MAC is similar in developed and developing countries but that broad mycobacterial immunity is greater in developing countries and may contribute to the lower rates of disseminated MAC infections in AIDS in these areas.

Isolation of Mycobacterium avium complex from water in the United States, Finland, Zaire, and Kenya.

Disseminated infection with organisms of the Mycobacterium avium complex (MAC) is a common complication of AIDS in the United States and other developing countries, but it is rare or absent in sub-Saharan Africa. To assess the comparative likelihood of exposure to MAC in these geographic areas, we used a standard protocol to culture 91 water samples from environmental sites and piped water supply systems in the United States, Finland, Zaire, and Kenya. MAC was isolated from all geographic areas and from 22 of 91 (24%) samples. Isolation rates were 13 of 47 (28%) for environmental samples and 9 of 44 (20%) for water supply samples. Overall isolation rates were 18 of 52 (35%) samples in the United States and Finland, whereas they were 4 of 39 (10%) samples in Zaire and Kenya (P = 0.015). MAC isolation rates from water supply systems were 8 of 25 (32%) samples in the United States and Finland and 1 of 19 (5%) samples in Zaire and Kenya (P = 0.056). MAC was isolated from hospital water in the United States and Finland but not in hospital water in Zaire and Kenya. Serovar determinations showed that six of eight isolates from the United States were serovar 4 or 8. One MAC isolate from Zaire was identified as an "X" mycobacterium. These data suggest that exposure to MAC in water is likely in diverse areas of the world, but that the likelihood of human exposure to the organism in water may be slightly less in sub-Saharan Africa than in developed countries in the Northern Hemisphere.

PIP: Between March 1990 and February 1992, microbiologists collected 91 water samples from various environmental sites (lakes, ponds, rivers, streams, harbors, marshes, and standing water) and from piped municipal and private water supply systems to determine the likelihood of human exposure to Mycobacterium avian complex (MAC) in New Hampshire and Boston in the US, Finland, Kenya, and Zaire. They wanted to examine the international distribution of MAC to determine whether the observation of AIDS patents in Africa not having MAC infection is association with differences in the environmental distribution of MAC. Overall isolation rates for environmental samples and for water supply samples stood at 28% and 20%, respectively. MAC isolation rates for all samples in the 2 developed countries were significantly higher than they were in the 2 Sub-Saharan African countries (35% vs. 10%; p = .015). The rates for water supply systems were higher in the US and Finland than they were in Kenya and Zaire (32% vs. 5%; p = .056). None of the water supply samples from hospitals in Kenya and Zaire tested positive for MAC, while about 20% in the US and 50% in Finland did. Serovars 4 and 8 of M. avian, which have been linked to infection in AIDS patients, accounted for 75% of the environmental M. avium isolates in the US. An X mycobacterium was found in an MAC isolate from Zaire. These findings indicate that the probability of human exposure to MAC in water is less than Sub-Saharan Africa than it is in developed countries in the northern hemisphere.