Sara H. Bares

Severe influenza in 33 US hospitals, 2013–2014: Complications and risk factors for death in 507 patients

BACKGROUND Influenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013-2014 influenza season. Little is known about the epidemiology of severe influenza during this season. METHODS A retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes. RESULTS A total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (>65 years, odds ratio, 3.1 [95% CI, 1.4-6.9], P=.006 and 50-64 years, 2.5 [1.3-4.9], P=.007; reference age 18-49 years), male sex (1.9 [1.1-3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9-37.0], P<.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2-1.4], P<.001). CONCLUSION Risk factors for death among US patients with severe influenza during the 2013-2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.

Bacterial and viral co-infections complicating severe influenza: Incidence and impact among 507 U.S. patients, 2013–14

Abstract Background Influenza acts synergistically with bacterial co-pathogens. Few studies have described co-infection in a large cohort with severe influenza infection. Objectives To describe the spectrum and clinical impact of co-infections. Study design Retrospective cohort study of patients with severe influenza infection from September 2013 through April 2014 in intensive care units at 33 U.S. hospitals comparing characteristics of cases with and without co-infection in bivariable and multivariable analysis. Results Of 507 adult and pediatric patients, 114 (22.5%) developed bacterial co-infection and 23 (4.5%) developed viral co-infection. Staphylococcus aureus was the most common cause of co-infection, isolated in 47 (9.3%) patients. Characteristics independently associated with the development of bacterial co-infection of adult patients in a logistic regression model included the absence of cardiovascular disease (OR 0.41 [0.23–0.73], p=0.003), leukocytosis (>11K/μl, OR 3.7 [2.2–6.2], p<0.001; reference: normal WBC 3.5–11K/μl) at ICU admission and a higher ICU admission SOFA score (for each increase by 1 in SOFA score, OR 1.1 [1.0–1.2], p=0.001). Bacterial co-infections (OR 2.2 [1.4–3.6], p=0.001) and viral co-infections (OR 3.1 [1.3–7.4], p=0.010) were both associated with death in bivariable analysis. Patients with a bacterial co-infection had a longer hospital stay, a longer ICU stay and were likely to have had a greater delay in the initiation of antiviral administration than patients without co-infection (p<0.05) in bivariable analysis. Conclusions Bacterial co-infections were common, resulted in delay of antiviral therapy and were associated with increased resource allocation and higher mortality.

Plasma and intracellular pharmacokinetics of tenofovir in patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide

Objectives: The aim of the study was to compare the intraindividual plasma and intracellular peripheral blood mononuclear cell (PBMC) pharmacokinetics of tenofovir (TFV) and its intracellular metabolite, TFV-diphosphate (TFV-DP) in patients switched from a fixed-dose combination (FDC) tablet of TFV disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir (EVG)/cobicistat (COBI) to a FDC containing TFV alafenamide (TAF)/FTC/EVG/COBI. Design: A single-arm, prospective, nonrandomized, cross-over, pharmacokinetic study in patients receiving a TDF-containing regimen (TDF 300 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg) switched to a TAF-containing FDC regimen (TAF 10 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg). Methods: Single, sparse plasma and PBMC samples were collected during TDF therapy and 4–8 weeks post-switch to the TAF-containing regimen. Plasma TFV and cell associated TFV-DP concentrations were determined with validated liquid chromatography tandem mass spectrometry methods. PBMC cell enumeration was performed by quantification of RNaseP (RPP30) gene copy numbers using a highly sensitive droplet digital PCR assay. Plasma and PBMC pharmacokinetics were summarized as geometric mean and compared as a geometric mean ratio with a Wilcoxon signed-rank test. Results: In 30 participants with evaluable data, TFV plasma concentrations decreased 90% [TDF: 99.98 (2.24) ng/ml vs. TAF: 10.2 (1.6) ng/ml, P < 0.001] after the switch while cell-associated TFV-DP increased 2.41-fold [TAF: 834.7 (2.49) vs. TDF: 346.85 (3.75) fmol/106 cells, P = 0.004]. Conclusion: Intraindividually, plasma TFV concentrations significantly decreased while cell associated TFV-DP concentrations significantly increased after switching from a TDF to a TAF-containing antiretroviral therapy regimen.

Acute suppurative parotitis caused by Streptococcus pneumoniae in an HIV-infected man

We report a case of a 32-year-old man who presented with progressive unilateral parotid gland enlargement and subsequently tested positive for HIV. A CT scan of the neck performed with contrast showed a phlegmon in the region of the right parotid tail measuring approximately 2.5×2.4 cm. Cultures of the aspirated fluid grew Streptococcus pneumoniae and the S. pneumoniae urinary antigen test was also positive. The patient underwent surgical debridement and received antimicrobial therapy with complete resolution of the parotitis. Parotitis caused by S. pneumoniae is rare, and HIV infection should be suspected in any case of invasive pneumococcal disease.

Myalgias and Joint Pain in a Traveler to India

A 54-year-old Indian female with no significant past medical history presented with fever, headache, myalgias, and joint pain which began while she was vacationing in India. Just 3 days before, she had returned from a 2-week trip to Delhi to visit family. One week into her stay in Delhi, she developed fevers up to 101 °F, headache, myalgias, and severe joint pain. She also had swelling and erythema of the wrists, knees, ankles, and feet. Two days later, she developed a pruritic rash that started on the legs and later spread to her trunk and arms. The patient’s father and brother-in-law reported similar symptoms.

Dolutegravir-induced colitis in an HIV-infected patient

Sir, Many of the gastrointestinal (GI) conditions associated with HIV disease have become much less frequent over the past two decades. Diarrhoea from opportunistic infections has become less common, and HIV-associated diarrhoea is now more often due to non-infectious causes such as ART-related adverse events and HIV enteropathy. Diarrhoea associated with ART is most commonly caused by PIs, which may damage the intestinal epithelial barrier and/or alter chloride ion secretion. Less is known about the diarrhoea associated with the other classes of ART. Newer antiretroviral agents offer improvements in potency and activity as well as tolerability. Dolutegravir was approved by the US FDA in August 2013 and is currently recommended as initial treatment in HIV-infected patients, both as part of the fixed-dose combination tablet including abacavir/lamivudine/dolutegravir and separately with tenofovir/emtricitabine. The efficacy of dolutegravir has been demonstrated in several randomized clinical trials (SPRING-1, SPRING-2, SINGLE, FLAMINGO and SAILING). – 7 In a recent safety review of dolutegravir, nausea, diarrhoea and headache were the most commonly reported treatment-related adverse effects. Diarrhoea occurred more often in patients on PI-based therapy (darunavir/ritonavir) than in those on dolutegravir, and the diarrhoea observed with dolutegravir was generally mild in intensity and typically did not prompt discontinuations or changes in treatment. Notably, treatment-emergent diarrhoea of at least moderate intensity occurred in ,1% of patients receiving dolutegravir. We report the case of a woman with chronic HIV infection who, after 18 months of treatment with abacavir/lamivudine and efavirenz, switched to abacavir/lamivudine and dolutegravir to accommodate a new job with a varied schedule including night shifts. The patient’s CD4 cell count was 780 cells/mm and HIV RNA concentration was ,20 copies/mL prior to making the ART change. Her medical history included chronic kidney disease stage 3, hyperlipidaemia, hypothyroidism, osteopenia and allergic rhinitis. Medications aside from ART included alendronate, cholecalciferol, levothyroxine, loratadine, montelukast and pravastatin, all of which she had been taking for at least 2 years. Approximately 3 weeks after the change from efavirenz to dolutegravir, she developed moderate diarrhoea characterized by 6–10 loose watery stools per day associated with urgency and occasional incontinence. She had no fevers or chills and denied any anorexia, nausea, vomiting or abdominal pain. She denied any sick contacts and had not received any recent antimicrobials or other new medications. The results of initial evaluations, including a stool assay for Clostridium difficile and a multiplex PCR test using the FilmArray GI Panel, which detects 22 common viruses, bacteria and parasites that cause infectious diarrhoea, were negative. Pathogens included in the FilmArray GI Panel are as follows: Campylobacter ( jejuni, coli and upsaliensis), Clostridium difficile (toxin A/B), Plesiomonas shigelloides, Salmonella, Yersinia enterocolitica, Vibrio species (including a specific target for Vibrio cholerae), enteroaggregative Escherichia coli, enteropathogenic E. coli, enterotoxigenic E. coli lt/st, Shiga-like toxin-producing E. coli stx1/stx2 (including a specific target for E. coli O157), Shigella/enteroinvasive E. coli, adenovirus F 40/41, astrovirus, norovirus GI/GII, rotavirus A, sapovirus (I, II, IV and V), Cryptosporidium, Cyclospora cayetanensis, Entamoeba histolytica and Giardia lamblia. The patient’s symptoms persisted for an additional 2 weeks, so she underwent colonoscopy with biopsy. The colon and terminal Figure 1. Apoptotic cells in the colon (haematoxylin and eosin stain×400). Research letters