Pharmacotherapy Approaches in Nontuberculous Mycobacteria Infections.

Nontuberculous mycobacteria (NTM) comprise a heterogeneous group of organisms, with only a small subset known to cause disease in humans. Although NTM infection is not a reportable disease, both the increasing clinical recognition and recent advancements in laboratory diagnostic capabilities of NTM infections in immunocompromised and immunocompetent patients are rapidly evolving. We reviewed antimicrobial agents used to treat the most frequently encountered NTM infections and examined optimized drug dosing strategies, toxicity profiles, drug-drug interactions, and the role of therapeutic drug monitoring. Antimicrobial susceptibility testing and patient monitoring on therapy were also examined. We used PubMed to review the published literature on the management of select NTM pathogens, the common syndromes encountered since 2000, and select pharmacokinetic principles of select antimicrobial agents used since 1990. We included select clinical trials, systematic reviews, published guidelines, and observational studies when applicable. The prolonged duration and the necessity for combination therapy for most forms of NTM disease can be problematic for many patients. A multidisciplinary care team that includes pharmacy engagement may help increase rates of optimal patient tolerability and successful treatment completion.

The Effect of Omega-3 Docosahexaenoic Acid Supplementation on Gestational Length: Randomized Trial of Supplementation Compared to Nutrition Education for Increasing n-3 Intake from Foods.

OBJECTIVE: DHA supplementation was compared to nutrition education to increase DHA consumption from fish and DHA fortified foods. DESIGN: This two-part intervention included a randomized double-blind placebo controlled DHA supplementation arm and a nutrition education arm designed to increase intake of DHA from dietary sources by 300 mg per day. SETTING: Denver Health Hospitals and Clinics, Denver, Colorado, USA. POPULATION: 871 pregnant women aged 18-40 were recruited between 16 and 20 weeks of gestation of whom 564 completed the study and complete delivery data was available in 505 women and infants. METHODS: Subjects received either 300 or 600 mg DHA or olive oil placebo or nutrition education. MAIN OUTCOME VARIABLE: Gestational length. RESULTS: Gestational length was significantly increased by 4.0-4.5 days in women supplemented with 600 mg DHA per day or provided with nutrition education. Each 1% increase in RBC DHA at delivery was associated with a 1.6-day increase in gestational length. No significant effects on birth weight, birth length, or head circumference were demonstrated. The rate of early preterm birth (1.7%) in those supplemented with DHA (combined 300 and 600 mg/day) was significantly lower than in controls. CONCLUSION: Nutrition education or supplementation with DHA can be effective in increasing gestational length.

Erythrocyte omega-6 and omega-3 fatty acids and mammographic breast density.

Diets low in omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and high in omega-3 (n-3) PUFAs may protect against breast cancer development. Associations of PUFA intake with mammographic density, an intermediate marker of breast cancer risk, have been inconsistent; however, prior studies have relied on self-reported dietary PUFA intake. We examined the association between circulating erythrocyte n-6 and n-3 PUFAs with mammographic density in 248 postmenopausal women who were not taking exogenous hormones. PUFAs in erythrocytes were measured by gas-liquid chromatography, and mammographic density was assessed quantitatively by planimetry. Spearman's correlation coefficients and generalized linear models were used to evaluate the relationships between PUFA measures and mammographic density. None of the erythrocyte n-6 or n-3 PUFA measures were associated with percent density or dense breast area.

Intravenous zoledronate improves bone density in adults with cystic fibrosis (CF).

OBJECTIVE: Reduced bone mineral density (BMD) and increased rates of atraumatic fracture are observed in cystic fibrosis (CF) patients, causing increasing morbidity as this population ages. The study aimed to assess the safety, tolerability and effect on BMD of intravenous zoledronate in adults with CF and osteopaenia. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: Adult CF outpatient clinics at two hospitals. PATIENTS: Twenty-two non-transplanted CF patients aged > or = 18 years with a bone densitometry T-score of < -1.5 at one of three sites (lumbar spine, femoral neck, distal forearm) were studied. Participants were randomized to receive either 2 mg zoledronate i.v. (n = 10) or normal saline (placebo, n = 12) every 3 months for 2 years (8 infusions). All participants received calcium and vitamin D supplements twice daily. MEASUREMENTS: Percentage change in areal BMD from baseline. RESULTS: Lumbar spine BMD increased from baseline more with zoledronate than placebo at 6 months (5.35 +/- 0.76 vs. 1.19 +/- 1.20%, P = 0.012), 12 months (6.6 +/- 1.5 vs. 0.35 +/- 1.55%, P = 0.011) and 24 months (6.14 +/- 1.86 vs. 0.44 +/- 0.10, P = 0.021). Femoral neck BMD increased more after zoledronate than placebo at 6 months (3.2 +/- 1.6 vs.-1.43 +/- 0.43%, P = 0.019), 12 months (4.12 +/- 1.8 vs.-1.59 +/- 1.4%, P = 0.024) and 24 months (4.23 +/- 1.3 vs.-2.5 +/- 1.41%, P = 0.0028). Forearm BMD did not change. Zoledronate was associated with flu-like and musculoskeletal side effects, particularly after the first infusion. There were no fractures in either group. CONCLUSION: Intravenous zoledronate was significantly more effective than placebo for increasing BMD in adults with CF and osteopaenia, but side effects limited its tolerability.

Skin and soft tissue infections due to rapidly growing mycobacteria: comparison of clinical features, treatment, and susceptibility.

OBJECTIVE: To compare the demographics, clinical features, susceptibility patterns, and treatment for skin and soft tissue infections due to Mycobacterium fortuitum and Mycobacterium chelonae or Mycobacterium abscessus. DESIGN: Retrospective medical record review. SETTING: Mayo Clinic, Rochester, Minn. PATIENTS: All patients seen at our institution with a positive culture for M chelonae, M abscessus, or M fortuitum from skin or soft tissue sources between January 1, 1987, and October 31, 2004. MAIN OUTCOME MEASURES: Patient demographics, clinical characteristics, therapeutic data, microbiological data, and outcomes. RESULTS: The medical records of 63 patients with skin or soft tissue infections due to rapidly growing mycobacteria were reviewed. Patients with M chelonae or M abscessus were older (61.5 vs 45.9 years, P<.001) and more likely to be taking immunosuppressive medications (60% vs 17%, P = .002) than patients with M fortuitum. Mycobacterium fortuitum tended to manifest as a single lesion (89% vs 38%, P<.001), while most M chelonae or M abscessus manifested as multiple lesions (62% vs 11%, P<.001). More patients with M fortuitum had a prior invasive surgical procedure at the infected site (56% vs 27%, P = .04). Patients with multiple lesions were more likely to be taking immunosuppressive medications than those with single lesions (67% vs 30%, P = .006). Seven patients failed treatment, several of whom were immunocompromised and had multiple comorbidities. CONCLUSIONS: Skin and soft tissue infections due to rapidly growing mycobacteria are associated with systemic comorbidities, including the use of immunosuppressive medications. There are significant differences in the demographic and clinical features of patients who acquire specific organisms, including association with immunosuppression and surgical procedures.

Diverticular disease in patients with colon cancer: subgroup analysis of national surgical adjuvant breast and bowel project protocol C-06.

BACKGROUND: Similar epidemiologic characteristics suggest a common etiology for colon cancer (CC) and diverticular disease of the colon (DD). The relationship between the 2 diseases is still unclear, and the impact of DD in patients diagnosed with CC on disease-free survival (DFS) and overall survival (OS) is unknown. National Surgical Adjuvant Breast and Bowel Project (NASBP) protocol C-06 is a clinical trial comparing oral uracil/tegafur/leucovorin with 5-fluorouracil/leucovorin in patients with resected stage II/III carcinoma of the colon. PATIENTS AND METHODS: The NASBP enrolled 1,608 patients who had undergone potentially curative resection for stage II/III colon cancer from 256 medical sites between February 14, 1997, and March 31, 1999. RESULTS: Pathology reports from 1561 eligible patients retrospectively reviewed for the presence of DD revealed that 160 (10.2%) had this disease. The median ages of patients with CC and DD and without DD were 67 and 61 years, respectively (P < 0.05). The majority of patients were white, and Hispanic patients were better represented in the group with DD (P < 0.05). Colon cancer was located in the rectosigmoid in 46.88% of patients with DD and in 31.92% of patients without DD (P < 0.05). A baseline diagnosis of DD made no significant contribution to DFS or OS without adjustment for confoundin factors (P = 0.2 and P = 0.32, respectively) or adjusted for Dukes classification and age (P = 0.49 and P = 0.68, respectively). CONCLUSION: The prevalence of DD in patients diagnosed and treated for CC was 10.2%. Patients with CC with and without DD differed from each other with respect to age, tumor location, and ethnicity. There was no negative impact of having DD on DFS and OS in patients treated for stage II/III CC.

Update on antiretroviral drug resistance testing: combining laboratory technology with patient care.

HIV drug resistance testing has been considered an emerging asset to modernized HIV management. Despite the increased number of antiretroviral agents currently available, virologic failure remains a significant problem. Drug resistance testing is designed to identify gene mutations or viral growth characteristics that suggest reduced drug susceptibility. The widespread use and virologic benefits of resistance testing in some prospective clinical trials have prompted the development of formal guidelines by expert panels for clinical use. Despite technological advances in drug resistance testing, clarification of assay interpretation, assay standardization, and the results from validation studies are needed. This review discusses updated genotyping and phenotyping methodologies, assay utilities and limitations, clinical validation studies, and current recommendations.

Iron deficiency in cystic fibrosis: relationship to lung disease severity and chronic Pseudomonas aeruginosa infection.

BACKGROUND: Iron deficiency (ID) is common in patients with cystic fibrosis (CF) and may be related to GI factors and chronic inflammation. Pseudomonas aeruginosa (PA) infection is predominantly responsible for chronic lung suppuration in patients with CF, but its survival is critically dependent on the availability of extracellular iron, which it obtains via highly efficient mechanisms. OBJECTIVE: To determine whether ID in CF patients is directly related to the severity of suppurative lung disease. DESIGN: We determined the iron status of 30 randomly selected adult CF patients (13 women) and assessed the relationship to lung disease severity and GI factors by determining their daily sputum volume, FEV(1) percent predicted, C-reactive protein (CRP) level, erythrocyte sedimentation rate, and degree of pancreatic supplementation. Additionally, we measured the sputum concentrations of iron and ferritin in a randomly selected subgroup of 13 of the 30 subjects. SETTING: Adult CF Service in a tertiary-care center. RESULTS: Seventy-four percent of subjects experienced ID (ie, serum iron levels < or = 12 micromol/L and/or transferrin saturation levels < or = 16%). There was no relationship found with the degree of pancreatic supplementation. The daily sputum volume was strongly associated with low serum iron levels, transferrin saturation, ferritin/CRP ratio, and FEV(1) percent predicted (p < 0.05). Serum iron levels and transferrin saturation were negatively related to CRP (r = -0.8 and r = -0.7, respectively; p < 0.01) and erythrocyte sedimentation rate (r = -0.5 and r = -0.4, respectively; p < 0.05). FEV(1) percent predicted was positively related to serum iron level (r = 0.5; p < 0.01), transferrin saturation (r = 0.4; p < 0.05), and ferritin/CRP ratio (r = 0.7; p < 0.05). Sputum iron concentration (median, 63 micromol/L; range, 17 to 134 micromol/L) and ferritin concentration (median, 5,038 microg/L; range, 894 to 6,982 microg/L) exceeded plasma levels and negatively correlated with FEV(1) percent predicted (r = -0.6 and r = -0.5, respectively; p < or = 0.05). CONCLUSION: In our CF patients, ID was directly related to the increased severity of suppurative lung disease but not to the degree of pancreatic insufficiency. Iron loss into the airway may contribute to ID and may facilitate PA infection.