Renuga Vivekanandan

Early versus late surgical intervention or medical management for infective endocarditis: A systematic review and meta-analysis

Objective Infective endocarditis is associated with high morbidity and mortality and optimal timing for surgical intervention is unclear. We performed a systematic review and meta-analysis to compare early surgical intervention with conservative therapy in patients with infective endocarditis. Methods PubMed, Cochrane, EMBASE, CINAHL and Google-scholar databases were searched from January 1960 to April 2015. Randomised controlled trials, retrospective cohorts and prospective observational studies comparing outcomes between early surgery at 20 days or less and conservative management for infective endocarditis were analysed. Results A total of 21 studies were included. OR of all-cause mortality for early surgery was 0.61 (95% CI 0.50 to 0.74, p<0.001) in unmatched groups and 0.41 (95% CI 0.31 to 0.54, p<0.001) in the propensity-matched groups (matched for baseline variables). For patients who had surgical intervention at 7 days or less, OR of all-cause mortality was 0.61 (95% CI 0.39 to 0.96, p=0.034) and in those who had surgical intervention within 8–20 days, the OR of mortality was 0.64 (95% CI 0.48 to 0.86, p=0.003) compared with conservative management. In propensity-matched groups, the OR of mortality in patients with surgical intervention at 7 days or less was 0.30 (95% CI 0.16 to 0.54, p<0.001) and in the subgroup of patients who underwent surgery between 8 and 20 days was 0.51 (95% CI 0.35 to 0.72, p<0.001). There was no significant difference in in-hospital mortality, embolisation, heart failure and recurrence of endocarditis between the overall unmatched cohorts. Conclusion The results of our meta-analysis suggest that early surgical intervention is associated with significantly lower risk of mortality in patients with infective endocarditis.

Incidence of ventilator associated pneumonia in burn patients with inhalation injury treated with high frequency percussive ventilation versus volume control ventilation: A systematic review

BACKGROUND Pneumonia increases mortality in burn patients with inhalation injuries. We evaluated whether the use of High Frequency Percussive Ventilation (HFPV) in burn patients with inhalation injuries can decrease rates of Ventilator Associated Pneumonia (VAP) compared to Volume Control Ventilation (VCV). METHODS Data were gathered from PubMed, EMBASE, Web of Science, reference lists, and hand search. For unpublished data we searched ClinicalTrials.gov and RePORTER. We included observational and Randomized Controlled Trials (RCTs) that compared rates of VAP with the use of HFPV and VCV in adult burn patients with inhalation injury. Two reviewers independently extracted data from the retrieved studies and assessed them for eligibility, methodology, and quality. RESULTS 281 abstracts were reviewed, of which 4 studies (540 patients) were included. Two were observational and two were RCTs. All studies had moderate risk of bias. One study had low external validity while others had moderate external validity. The two observational studies found non-concordant results. One study found a 24% statistically significant reduction in the rates of VAP while the other found no difference. The two RCTs had small sample sizes. There was no significant difference in VAP rates between HFPV and VCV. The VCV arms of the four studies were heterogeneous. Only one study used low tidal volumes, whereas the rest used high tidal volumes in the VCV arm. CONCLUSION Evidence about decreased incidence of VAP in burn patients with inhalation injuries who are on HFPV compared to those on VCV is inconclusive. Although enhanced airway clearance by HFPV was thought to play a role in decreasing VAP in this population, high tidal volume in the VCV arms could be a confounding factor that should be eliminated in future studies before a firm conclusion can be reached. More RCTs comparing HFPV to low tidal volume VCV are needed.

Hepatitis C therapy: Looking toward interferon-sparing regimens

OBJECTIVE To describe chronic hepatitis C virus (HCV) infection, including its epidemiology and pathophysiology; review current treatment options for HCV infection; recognize investigational agents being studied as part of interferon-free therapy; and summarize clinical trials for the new agents. DATA SOURCES PubMed for 2004 through August 2014 using search terms hepatitis C, American Association for the Study of Liver Diseases, sofosbuvir, simeprevir, and as needed specific names of other agents in development during this time; news articles and news releases about company actions with regard to clinical trials and filings for marketing approval in the United States. STUDY SELECTION At the discretion of the author based on clinical relevance of study and relevance to national guidelines for HCV therapy. RESULTS HCV infection is an important medical and public health problem in the United States and worldwide that can cause cirrhosis, hepatocellular carcinoma, and liver failure. The advent of newly developed targeted therapies is changing the treatment paradigm for this disease. Although traditional therapy with pegylated interferon and ribavirin remain therapeutic options, direct-acting agents such as sofosbuvir (Sovaldi-Gilead) and simeprevir (Olysio-Janssen) are producing faster, earlier, and improved treatment response with fewer adverse effects. The combination of anti-HCV agents and the duration of treatment are based on genotype, patient treatment status, and patient risk factors. The dramatic and sustained clearance of the virus with these drugs makes sustained virologic response a reality for patients who are unable to tolerate pegylated interferon. The downside is their high cost, which may make them economically unsustainable. However, for patients infected with HCV, the potential for a cure and improved quality of life may now be a reality. CONCLUSION HCV, a well-known blood-borne disease associated with significant morbidity and mortality worldwide, can be effectively and safely treated with new anti-HCV agents such as SOF. While these new medications are in their early days of real-world practice, they offer hope that cure is truly possible.

Topical Tenofovir Disoproxil Fumarate Nanoparticles Prevent HIV-1 Vaginal Transmission in a Humanized Mouse Model

ABSTRACT Preexposure prophylaxis (PrEP) with 1% tenofovir (TFV) vaginal gel has failed in clinical trials. To improve TFV efficacy in vaginal gel, we formulated tenofovir disoproxil fumarate nanoparticles in a thermosensitive (TMS) gel (TDF-NP-TMS gel). TDF-NPs were fabricated using poly(lactic-co-glycolic acid) (PLGA) polymer and an ion-pairing agent by oil-in-water emulsification. The efficacy of TDF-NP-TMS gel was tested in humanized bone marrow-liver-thymus (hu-BLT) mice. Hu-BLT mice in the treatment group (Rx; n = 15) were administered TDF-NP-TMS gel intravaginally, having TDF at 0.1%, 0.5%, and 1% (wt/vol) concentrations, whereas the control (Ctr; n = 8) group received a blank TMS gel. All Rx mice (0.1% [n = 4], 0.5% [n = 6], and 1% [n = 5]) were vaginally challenged with two transmitted/founder (T/F) HIV-1 strains (2.5 × 105 50% tissue culture infectious doses). Rx mice were challenged at 4 h (0.1%), 24 h (0.5%), and 7 days (1%) posttreatment (p.t.) and Ctr mice were challenged at 4 h p.t. Blood was drawn weekly for 4 weeks postinoculation (p.i.) for plasma viral load (pVL) using reverse transcription-quantitative PCR. Ctr mice had positive pVL within 2 weeks p.i. Rx mice challenged at 4 h and 24 h showed 100% protection and no detectable pVL throughout the 4 weeks of follow-up (P = 0.009; Mantel-Cox test). Mice challenged at 7 days were HIV-1 positive at 14 days p.i. Further, HIV-1 viral RNA (vRNA) in vaginal and spleen tissues of Rx group mice with negative pVL were examined using an in situ hybridization (ISH) technique. The detection of vRNA was negative in all Rx mice studied. The present studies elucidate TDF-NP-TMS gel as a long-acting, coitus-independent HIV-1 vaginal protection modality.

Education and Communication in an Interprofessional Antimicrobial Stewardship Program

CONTEXT Interprofessional education/interprofessional practice (IPE/IPP) is an essential component in medical education and training. A collaborative interprofessional team environment ensures optimal patient-centered care. OBJECTIVE To describe the implementation of 2 interprofessional antimicrobial stewardship program (ASP) teams using IPE/IPP and to assess the acceptance rate by the primary medical and surgical teams of ASP recommendations for antimicrobial interventions. METHODS A business plan for the ASP was approved at 2 academic medical centers used for the present study. During a 3-year study period, 2 interprofessional ASP teams included an attending physician specializing in infectious disease (ID), an ID physician fellow, an ASP pharmacist, physician residents, medical students, pharmacy residents, and pharmacy students. Educational seminars were presented for all adult-admitting physicians to discuss the need for the ASP and the prospective audit and feedback process. Cases were presented for discussion during ASP/ID rounds and recommendations were agreed upon by the ASP team. A motivational interviewing face-to-face technique was frequently used to convey the ASP team recommendation to the primary medical or surgical team in a noncoercive and educational manner. The ASP team recommendations for ASP interventions were documented in the medical records. RESULTS The overall acceptance rate of recommendations by the primary medical and surgical teams were greater than 90% (2051 of 2266). The most frequent interventions provided were streamline therapy (601), route of administration change (452), bug-drug mismatch (190), and discontinuation of therapy (179). Route of administration change was also the most frequently accepted intervention (96%). CONCLUSIONS The motivational face-to-face communication technique was particularly useful in conveying ASP team member recommendations to the primary medical or surgical teams. Communicating recommendations as a multidisciplinary team in an educational manner seems to have resulted in to greater acceptance of recommendations.

Mycotic pseudoaneurysm by vancomycin-intermediate Staphylococcus aureus: a rare cause of persistent bacteraemia

Pseudoaneurysms are vessel wall ruptures, that are often mistaken for deep vein thrombosis (DVT). A middle-aged man presented with right leg pain, swelling and erythema. His history was significant for persistent Staphylococcus aureus bacteraemia. Ultrasound revealed subacute DVT and laboratory parameters were suggestive of sepsis. He was started on intravenous heparin and antimicrobials. Owing to persistent anaemia despite blood transfusion, MRI of the right thigh was obtained. It revealed a 13×17 cm superficial femoral artery infected mycotic pseudoaneurysm (MPA) with a fresh haematoma. The patient underwent arterial ligation and extensive debridement. Intraoperative cultures revealed daptomycin-resistant vancomycin-intermediate S. aureus (VISA) and he was managed with 6 weeks of intravenous ceftaroline. MPAs are most common in the femoral artery and form <1% of aneurysms. Therapy involves surgical debridement and prolonged antimicrobials. VISA causing MPA is associated with worse outcomes. We report the first time use of ceftaroline in the management of a VISA MPA.

A Rare Manifestation of Tuberculosis Presenting in the United States

A 64-year-old Bangladeshi female presented to her primary care physician with a tender right breast lump that had been present for 4-5 days along with subjective fevers and malaise. Initial biopsy revealed granulomas, but Ziehl-Neelsen and Gram stain were negative for TB so antibiotics were prescribed for abscess until culture came positive for tuberculosis. She was started on triple therapy for extrapulmonary tuberculosis, an exceedingly rare presentation that requires high clinical suspicion in the Western world.

Fatal Case of Probable Invasive Aspergillosis after Five Years of Heart Transplant: A Case Report and Review of the Literature

Invasive fungal infections are very common in solid organ transplants and occur most frequently in the first three months after transplant. A 49-year-old female with a history of two remote heart transplants with the most recent one occurring 5 years ago was admitted for increasing shortness of breath, cough, and fever. Computerized tomography (CT) scan of the chest showed left lower lung ground-glass and tree-in-bud opacities. She was started on broad spectrum antibiotics along with ganciclovir and micafungin. Ganciclovir was added due to the patients past history of CMV infection and empiric fungal coverage with micafungin. Bronchoalveolar lavage (BAL) was performed as her respiratory status worsened and voriconazole was added for possible aspergillosis in combination therapy with micafungin. BAL galactomannan returned positive which was suggestive of aspergillosis. Patient worsened clinically and subsequently succumbed to cardiorespiratory arrest despite our best efforts. It is important to have a high degree of clinical suspicion for invasive aspergillosis in transplant patients even many years after transplant and initiate aggressive therapy due to poor outcomes.

Multidrug-resistant Nocardia pseudobrasiliensis presenting as multiple muscle abscesses.

A 79-year-old Caucasian man presented with multiple leg abscesses due to Nocardia pseudobrasiliensis. He was on chronic steroid therapy for myasthenia gravis. We present the difficulties in diagnosis and treatment of this rare organism. N. pseudobrasiliensis is a new emerging species that was previously thought to belong to the N. brasiliensis species. The distinction between the two species is extremely important given the different antibiotic susceptibility pattern and association of N. pseudobrasiliensis with more invasive and disseminated disease.

False-positive tuberculous meningitis due to laboratory contamination: importance of a holistic clinical evaluation

Incidence of tuberculosis in Nebraska is 1.9/100 000 people. Tuberculous meningitis is rare and comprises 1% of extrapulmonary tuberculosis. An elderly Caucasian man presented with fever, headache, altered mentation and a history of tick bite. Cerebrospinal fluid (CSF) analysis showed negative cultures and the patient was treated empirically for tickborne illness. Forty-five days later, CSF nucleic acid amplification test (NAAT) was positive for tuberculosis. On readmission, repeat neurological examination and CSF analysis were benign and the patient was not offered antituberculous treatment. Genotype investigation of the culture and NAAT specimen by the Center for Disease Control confirmed laboratory contamination. The literature reports an incidence of 2–4% for false-positive tuberculosis cultures. Contaminated devices, clerical errors and laboratory errors have been implicated. Laboratory contamination results in smear-negative culture-positive cases. Epidemiological investigation with genotype testing is confirmatory. Detailed clinical assessment with good clinical and laboratory communication and frequent laboratory surveillance is advocated to mitigate these cases.