Infectious Disease

Singh, N., C. D. Sifri, F. P. Silveira, R. Miller, K. S. Gregg, S. Huprikar, E. D. Lease, A. Zimmer, J. S. Dummer, C. W. Spak, C. Koval, D. B. Banach, M. Shroff, J. Le, D. Ostrander, R. Avery, A. Eid, R. R. Razonable, J. Montero, E. Blumberg, A. Alynbiawi, M. I. Morris, H. B. Randall, G. Alangaden, J. Tessier, T. V. Cacciarelli, M. M. Wagener and H. Y. Sun (2016). “Unique characteristics of cryptococcosis identified after death in patients with liver cirrhosis: Comparison with concurrent cohort diagnosed antemortem.” Med Mycol: 2016 Sep [Epub ahead of print].

Full text of this article.

Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers.

Edmonds, J. K., L. A. Campbell and R. E. Gilder (2016). “Public health nursing practice in the affordable care act era: A national survey.” Public Health Nurs: 2016 Jul [Epub ahead of print].

Full text of this article.

OBJECTIVES: To explore public health nurses’ knowledge, perceptions, and practices under the Affordable Care Act (ACA). DESIGN AND SAMPLE: A cross-sectional, web-based survey was completed by a sample of 1,143 public health nurses (PHNs) in the United States. MEASURES: Descriptive statistics were analyzed for variables related to general knowledge and perception of the ACA and for the extent of involvement in activities related to the implementation of the ACA. Qualitative analysis was conducted on free text comments to two open-ended questions about current and future PHNs involvement in the ACA. RESULTS: Approximately 45% of PHNs reported changes in their daily work due to the ACA. PHNs reported being very or somewhat involved in these activities of the ACA: integration of primary care and public health (62%), provision of clinical preventive services (60.3%), care coordination (55.4%), patient navigation (55.3%), establishment of private-public partnerships (55.3%), population health strategies (53.6%), population health data assessment and analysis (53.8%), community health assessments (49%), involvement in medical homes (37.8%), provision of maternal and child health home visiting services (32.1%), and involvement in Accountable Care Organizations (29.2%). CONCLUSION: PHNs are making substantial contributions to implementation of the ACA.

Tran, T. and S. G. Beal (2016). “Application of the 1,3-beta-d-Glucan (Fungitell) Assay in the Diagnosis of Invasive Fungal Infections.” Arch Pathol Lab Med 140(2): 181-185.

Full text of this article.

With the high mortality rate associated with invasive fungal infections, methods for timely detection and diagnosis are necessary for appropriate and effective treatment. Testing for 1,3-beta-d-glucan, a cell wall component of many medically important fungi, can be a useful adjunct in diagnosing such infections. The Fungitell assay (Associates of Cape Cod, East Falmouth, Massachusetts) is a US Food and Drug Administration-approved laboratory test that quantitatively measures 1,3-beta-d-glucan levels and is widely available for clinical use as a relatively noninvasive method to aid in detecting the presence of invasive fungal infections. Numerous studies have evaluated its performance in clinical settings, and results have, overall, been favorable. It is not without its drawbacks, however, and the test must be interpreted and applied with care. Ordering practices are also widely variable among clinicians, and official guidelines have not been readily available. We present the details of this test and aim to propose evidence-based guidance for its use.

Shenje, J., F. I. Adimora-Nweke, I. L. Ross, M. Ntsekhe, L. Wiesner, A. Deffur, H. M. McIlleron, J. Pasipanodya, T. Gumbo and B. M. Mayosi (2015). “Poor Penetration of Antibiotics Into Pericardium in Pericardial Tuberculosis.” Ebiomedicine 2(11): 1640-1649.

Full text of this article.

Pericardial tuberculosis (TB) is associated with high therapy failure and high mortality rates. Antibiotics have to penetrate to site of infection at sufficient non-protein bound concentrations, and then enter bacteria to inhibit intracellular biochemical processes. The antibiotic concentrations achieved in pericardial fluid in TB pericarditis have never been measured before. We recruited two cohorts of patients with TB pericarditis, and left a pigtail catheter in-situ for serial drug concentration measurements over 24 h. Altogether, 704 drug concentrations were comodeled for pharmacokinetic analyses. The drug concentrations achieved in pericardial fluid were compared to the minimum inhibitory concentrations (MICs) of clinical Mycobacterium tuberculosis isolates. The total rifampicin concentration pericardial-to-serum ratios in 16 paired samples were 0.19 +/- 0.33. The protein concentrations of the pericardial fluid in TB pericarditis were observed to be as high as in plasma. The non-protein bound rifampicin concentrations in pericardial fluid were 4-fold lower than rifampicin MICs in the pilot study, and the peak concentration was 0.125 versus 0.208 mg/L in the second (p = 0.001). The rifampicin clearance from pericardial fluid was 9.45 L/h versus 7.82 L/h in plasma (p = 0.002). Ethambutol peak concentrations had a pericardial-to-plasma ratio of 0.55 +/- 0.22; free ethambutol peak concentrations were 2.30-lower than MICs (p < 0.001). The pericardial fluid pH was 7.34. The median pyrazinamide peak concentrations were 42.93mg/L versus a median MIC of 800mg/L at pH 7.34 (p < 0.0001). There was no significant difference between isoniazid pericardial fluid and plasma concentrations, and isoniazid peak concentrations were above MIC. This is the first study to measure anti-TB drug concentrations, pH and protein in the pericardial TB fluid. Pericardial concentrations of the key sterilizing drugs for TB were below MIC, which could contribute to poor outcomes. A new regimen that overcomes these limitations might need to be crafted. (C) 2015 The Authors. Published by Elsevier B.V.

Pasipanodya, J. G., M. Mubanga, M. Ntsekhe, S. Pandie, B. T. Magazi, F. Gumedze, L. Myer, T. Gumbo and B. M. Mayosi (2015). “Tuberculous Pericarditis is Multibacillary and Bacterial Burden Drives High Mortality.” Ebiomedicine 2(11): 1634-1639.

Full text of this article.

Background: Tuberculous pericarditis is considered to be a paucibacillary process; the large pericardial fluid accumulation is attributed to an inflammatory response to tuberculoproteins. Mortality rates are high. We investigated the role of clinical and microbial factors predictive of tuberculous pericarditis mortality using the artificial intelligence algorithm termed classification and regression tree (CART) analysis. Methods: Patients were prospectively enrolled and followed in the Investigation of the Management of Pericarditis (IMPI) registry. Clinical and laboratory data of 70 patients with confirmed tuberculous pericarditis, including time-to-positive (TTP) cultures from pericardial fluid, were extracted and analyzed for mortality outcomes using CART. TTP was translated to log(10) colony forming units (CFUs) per mL, and compared to that obtained from sputum in some of our patients. Findings: Seventy patients with proven tuberculous pericarditis were enrolled. The median patient age was 35 (range: 20-71) years. The median, follow up was for 11.97 (range: 0 . 03-74.73) months. The median TTP for pericardial fluid cultures was 22 (range: 4-58) days or 3.91(range: 0 . 5-8 . 96) log(10)CFU/mL, which overlapped with the range of 3.24-7.42 log(10)CFU/mL encountered in sputum, a multi-bacillary disease. The overall mortality rate was 1.43 per 100 person-months. CART identified follow-up duration of 5 . 23 months on directly observed therapy, a CD4+ count of <= 199.5/mL, and TTP <= 14 days (bacillary load >= 5.53 log(10) CFU/mL) as predictive of mortality. TTP interacted with follow-up duration in a non-linear fashion. Interpretation: Patients with culture confirmed tuberculous pericarditis have a high bacillary burden, and this bacterial burden drivesmortality. Thus proven tuberculosis pericarditis is not a paucibacillary disease. Moreover, the severe immunosuppression suggests limited inflammation. There is a need for the design of a highly bactericidal regimen for this condition. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).