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What's new in infectious diseases

Disclosures: Elinor L Baron, MD, DTMH Employee of UpToDate, Inc. Allyson Bloom, MD Employee of UpToDate, Inc. Anna R Thorner, MD Employee of UpToDate, Inc. Jennifer Mitty, MD, MPH Employee of UpToDate, Inc.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2014. | This topic last updated: Dec 18, 2014.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ANTIMICROBIAL AGENTS

Trimethoprim-sulfamethoxazole and sudden death (December 2014)

While trimethoprim-sulfamethoxazole (TMP-SMX) has generally been felt to be well tolerated, a case-control study found an association between sudden death, possibly due to hyperkalemia, and prescription of TMP-SMX among older patients who were also receiving an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) [1].Those who received TMP-SMX had an increased seven-day risk of sudden death compared with those who received amoxicillin (adjusted odds ratio 1.38, 95% CI 1.09-1.76). However, other factors that affected the choice of antibiotic may have confounded these results, and higher quality evidence is needed to determine whether this association is causal. (See "Trimethoprim-sulfamethoxazole: An overview", section on 'Life threatening effects'.)

Prophylactic antibiotics do not benefit patients with acute liver failure (October 2014)

The role of prophylactic antibiotics in the treatment of patients with acute liver failure is controversial. In a retrospective study of 1551 patients with acute liver failure, antimicrobial prophylaxis did not reduce the incidence of bloodstream infection or mortality [2]. Our approach to antibiotic prophylaxis is to not give patients prophylactic antibiotics, but instead give antibiotics only if there is evidence of active infection, positive surveillance culture results, or clinical deterioration. (See "Acute liver failure in adults: Management and prognosis", section on 'Infection surveillance and prevention'.)

Antibiotic decontamination of the digestive tract in the ICU and antimicrobial resistance (October 2014)

The use of prophylactic antibiotics to decontaminate the oropharyngeal and/or digestive tracts of critically ill patients and reduce the risk of infection confers a modest mortality benefit but is not widely used, in part, because of concern that it can promote antimicrobial resistance. A large multicenter cluster-randomized trial in intensive care units in the Netherlands compared resistance rates with selective oropharyngeal decontamination (SOD; antibiotics applied to the oropharynx only) and selective digestive decontamination (SDD; antibiotics applied to the oropharynx and through a nasogastric tube plus a different intravenous antibiotic) [3]. Rates of rectal colonization with highly resistant bacteria were overall lower with SDD than SOD, but colonization with aminoglycoside-resistant gram-negative bacilli increased more over time with SDD than SOD. Given the very low baseline rate of antimicrobial resistance in the Netherlands and the absence of a control group that received no prophylactic antibiotics, these findings do not sufficiently allay concerns about long-term antimicrobial resistance with antibiotic use for decontamination of the gastrointestinal tract. (See "Epidemiology and prevention of infections and antimicrobial resistance in the intensive care unit", section on 'Decontamination of the digestive tract'.)

Safety of fluoroquinolones in children (June 2014)

Fluoroquinolones are not recommended for routine use in children <18 years of age because studies in immature animals have demonstrated the development of arthropathy with erosions of the cartilage in weight-bearing joints. A study evaluated the risk of musculoskeletal toxicity during five years of follow-up in children who received levofloxacin or a comparator for acute otitis media or community-acquired pneumonia [4]. Of children identified with a musculoskeletal adverse event, the number that were considered “possibly related” to drug therapy was equally low in both groups. No musculoskeletal adverse event was considered “likely related” to levofloxacin. Nevertheless, until further data are available to confirm these findings, the use of fluoroquinolones in children should be limited to the treatment of infections for which no safe and effective alternative exists. (See "Fluoroquinolones", section on 'Use in children'.)

Cardiovascular outcomes and azithromycin use for pneumonia (June 2014)

Large observational studies have shown conflicting results with regards to a possible increase in cardiovascular mortality associated with azithromycin use. A more recent large cohort study evaluated the association between azithromycin use and all-cause mortality and cardiovascular events in more than 60,000 United States veterans ≥65 years of age who were hospitalized with pneumonia [5]. Ninety-day mortality was significantly lower in those who were treated with an azithromycin-containing regimen versus those who received other guideline-concordant antibiotics. Compared with patients who did not receive azithromycin, those who received azithromycin were slightly more likely to have a myocardial infarction, but not arrhythmias, heart failure, or any cardiac event. An analysis of these data suggested that seven deaths were averted for each non-fatal myocardial infarction associated with azithromycin use, reflecting a net benefit of azithromycin for patients ≥65 years of age with pneumonia. (See "Azithromycin, clarithromycin, and telithromycin", section on 'QT interval prolongation and cardiovascular events'.)

New antibiotics with activity against MRSA for skin and skin structure infections (June 2014, MODIFIED June 2014)

Antibiotic options for the treatment of skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are growing. Dalbavancin and oritavancin have a similar mechanism of action and spectrum of activity to vancomycin, but can be administered as once-weekly intravenous doses because of long half-lives. Tedizolid is from the same antibiotic class as linezolid and can be administered intravenously or orally once daily. In several large randomized trials of adults with acute cellulitis, wound infections, and abscesses, including infections caused by MRSA, these new agents had efficacy and safety profiles similar to vancomycin and/or linezolid with more convenient dosing [6-8]. Dalbavancin, tedizolid, and oritavancin have been approved for skin and skin structure infections by the U.S. Food and Drug Administration in 2014. (See "Treatment of invasive methicillin-resistant Staphylococcus aureus infections in adults", section on 'Dalbavancin' and "Treatment of invasive methicillin-resistant Staphylococcus aureus infections in adults", section on 'Oritavancin'.)

BACTERIAL INFECTIONS

Infection associated with contaminated endoscopes (October 2014)

In January 2014, the Centers for Disease Control and Prevention (CDC) reported that since January 2013, 69 cases of New Delhi metallo-beta-lactamase (NDM)-producing carbapenem-resistant Enterobacteriaceae (CRE) had been identified in the United States, 44 of which were from northeastern Illinois [9]. Further investigation identified 39 cases from one hospital [10]. The source of infection was subsequently traced to the elevator channel of a single duodenoscope (the endoscopes used for endoscopic retrograde cholangiopancreatography [ERCP]). No lapses in the cleaning protocol were identified. It is theorized that the complex design of the elevator mechanism makes it more difficult to clean than other parts of endoscopes [10,11]. After changing duodenoscope reprocessing from high-level disinfection to gas sterilization with ethylene oxide, no new cases have been identified. Duodenoscopes should be considered as possible sources for CRE outbreaks in healthcare facilities. (See "Endoscope disinfection", section on 'Carbapenem-resistant Enterobacteriaceae'.)

Prophylactic antibiotics before laparoscopic cholecystectomy (September 2014)

Multiple meta-analyses of randomized trials comparing antibiotic prophylaxis with no antibiotic or placebo prior to elective laparoscopic cholecystectomy have found no differences in the incidence of surgical site infection. These trials have generally included 50 to 175 patients in each arm and have used a single dose of antibiotics administered just prior to surgery. A subsequent large trial randomly assigned approximately 1000 low-risk patients undergoing elective laparoscopic cholecystectomy to no antibiotics or intravenous antibiotics given preoperatively and at 12 and 24 hours postoperatively [12]. In this later trial, the incidence of surgical site infection was lower for those who received perioperative antibiotics (0.8 versus 3.7 percent without antibiotics). Despite the added cost of antibiotic administration, overall hospital costs were lower in the prophylaxis group. Further investigation is needed to determine whether the infectious risk reduction of additional antibiotic doses outweighs the risks of toxicity or bacterial drug resistance associated with increased antibiotic usage. (See "Laparoscopic cholecystectomy", section on 'Antibiotics'.)

Perioperative asymptomatic bacteriuria and prosthetic joint infection (August 2014)

Some clinicians screen and treat for asymptomatic bacteriuria prior to joint arthroplasty, but evidence to support this practice is lacking. Although asymptomatic bacteriuria was associated with subsequent prosthetic joint infection in a prospective study of nearly 2500 patients undergoing total hip or knee arthroplasty, treatment of the bacteriuria, which was at the discretion of the clinician, was not associated with a decreased risk of infection [13]. Furthermore, the organisms isolated from the urine were not the same as those from the surgical site infection in any patient. Although asymptomatic bacteriuria may be a marker for individuals at higher risk for subsequent prosthetic joint infection, it appears unlikely to be causative. We do not routinely perform urinalysis or culture in patients without urinary symptoms prior to or following joint arthroplasty. (See "Approach to the adult with asymptomatic bacteriuria", section on 'Patients undergoing joint arthroplasty'.)

Next-generation DNA sequencing for pathogen identification (June 2014)

Next-generation sequencing (NGS) is a method for determining DNA sequence by analyzing multiple DNA fragments in parallel; it allows sequencing of an exponentially greater number of genes than conventional DNA sequencing. Although NGS has been applied to the diagnosis of complex genetic disorders, a new report suggests it may also be helpful in identifying an infectious pathogen when microbial or serologic testing is unrevealing [14]. NGS was performed on the cerebrospinal fluid of a 14-year-old boy with unexplained fever and progressive neurologic deterioration in whom an extensive infectious disease evaluation had been negative. A species of Leptospira was identified, and antibiotic therapy was initiated with rapid clinical improvement. Subsequent testing confirmed the diagnosis. (See "Principles and clinical applications of next-generation DNA sequencing", section on 'Indications for next-generation sequencing'.)

FUNGAL INFECTIONS

Fatality due to contaminated probiotic in a preterm infant (November 2014)

In October 2014, a fatal case of mucormycosis caused by Rhizopus oryzae was reported in a premature infant who received the probiotic supplement Solgar ABC Dophilus® Powder for prevention of necrotizing enterocolitis (NEC) [15]. Investigation by the Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), and Connecticut Departments of Public Health and Consumer Protection of the same lot of unopened Solgar ABC Dophilus® Powder revealed contamination with Rhizopus oryzae. As a result, the CDC sent out a Health Alert on November 25, 2014 that recommends Solgar ABC Dophilus not be used in infants, and that any patient who received this product in the last 30 days be evaluated and empiric antifungal therapy be considered in consultation with an infectious disease specialist. This case supports our current practice of NOT routinely using probiotic therapy to prevent NEC until strict criteria are met for manufacturing and regulation of probiotic products, and there are reliable data for optimal administration of these products. (See "Mucormycosis (zygomycosis)", section on 'Healthcare-associated' and "Prevention of necrotizing enterocolitis in newborns", section on 'Probiotics'.)

T2Candida assay for the detection of candidemia (September 2014)

In 2014, the US Food and Drug Administration (FDA) cleared the T2Candida assay for the detection of bloodstream infection caused by C. albicans, C. tropicalis, C. parapsilosis, C. glabrata, and/or C. krusei [16]. The T2Candida test uses magnetic resonance technology to detect these pathogens from a blood specimen within three to five hours, but a specialized instrument is required to perform the assay. It has a sensitivity of 84 to 96 percent and a specificity of nearly 100 percent. The clinical utility of this technique requires further study. (See "Clinical manifestations and diagnosis of candidemia and invasive candidiasis in adults", section on 'T2Candida'.)

GLOBAL HEALTH

Efficacy of the dengue vaccine CYD-TDV (January 2014, MODIFIED November 2014)

No licensed vaccine is available for preventing dengue; thus far CYD-TDV, a live attenuated tetravalent vaccine, is the most promising. Two large trials were published in 2014 evaluating the efficacy of the vaccine. In these randomized, placebo-controlled trials, conducted in over 30,000 children in the Asia-Pacific region, Latin America, and the Caribbean, the vaccine efficacy of three CYD-TDV doses against virologically confirmed dengue was 57 to 61 percent in the intention-to-treat analyses [17,18]. The vaccine efficacy against dengue hemorrhagic fever after three doses was 89 to 95 percent. Therefore, this vaccine is most effective for protection against severe disease. Vaccine efficacy varied by serotype, and was least protective against serotype 2. The epidemiologic threshold of dengue activity upon which national vaccination programs are justified has yet to be determined. (See "Prevention and treatment of dengue virus infection", section on 'Vaccination'.)

Ebola outbreak in 2014 (August 2014, MODIFIED October 2014)

The largest outbreak of Ebola virus infection reported to date is occurring in West Africa. The countries with widespread transmission include Guinea, Liberia, and Sierra Leone [19]. Patients with Ebola virus disease have also been reported in Mali. Cases outside of West Africa have occurred in healthcare workers caring for patients with Ebola virus disease, as well as a returning traveler. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have provided information to help clinicians evaluate and manage patients with suspected Ebola virus disease [20,21]. The decision to test an individual who may have been exposed to Ebola virus depends upon when the potential exposure occurred, the risk of exposure, and whether or not the individual is displaying signs and symptoms consistent with Ebola virus disease (eg, fever, severe headache, myalgias, gastrointestinal symptoms, or unexplained hemorrhage). If testing is indicated, patients should be isolated. Infection control precautions include standard, contact, and droplet precautions, as well as the correct use of appropriate personal protective equipment [22,23]. Clinicians can refer to the CDC and WHO websites for additional information. (See "Clinical manifestations and diagnosis of Ebola virus disease" and "Epidemiology and pathogenesis of Ebola virus disease".)

HIV INFECTION

Efficacy of second-line antiretroviral regimens in resource-limited settings (September 2014)

In resource-limited settings, the choice of an antiretroviral regimen for HIV infection following virologic failure with an initial regimen must often be made without knowledge of the presence of resistance mutations. There has been concern that drug resistance following failure of a nucleoside reverse transcriptase inhibitor (NRTI) based regimen would render subsequent NRTI-based regimens less effective. However, in a trial from sub-Saharan Africa that included 1277 HIV-infected individuals who had failed treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two NRTIs, rates of virologic suppression were similar with a boosted protease inhibitor plus two to three NRTIs or plus an integrase inhibitor (88 and 87 percent, respectively) [24]. Virologic suppression rates with boosted protease inhibitor monotherapy were lower. These data support the World Health Organization recommendations to use a boosted protease inhibitor with at least two NRTIs as a second line regimen in resource limited settings. (See "The impact of antiretroviral therapy on morbidity and mortality of HIV infection in resource-limited settings", section on 'Drug resistance'.)

Treatment guidelines for adults with HIV infection (July 2014)

The 2014 International Antiviral Society-USA panel (IAS-USA) has published antiretroviral treatment guidelines for adults with HIV infection [25]. These guidelines are generally in agreement with the 2014 Department of Health and Human Services panel recommendations [26]. ART should be initiated for virtually all treatment-naïve HIV-infected individuals. Recommended regimens contain a backbone of two different nucleoside/nucleotide reverse transcriptase inhibitors, and a third drug, which may be an integrase inhibitor, a non-nucleoside reverse transcriptase inhibitor, or a boosted protease inhibitor. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient", section on 'Recommendations of others'.)

Suicidality among HIV-infected individuals receiving efavirenz (July 2014)

Efavirenz is a non-nucleoside reverse transcriptase inhibitor that is often included as part of a first-line antiretroviral regimen for treatment-naïve HIV-infected individuals. Recent data suggest that efavirenz is associated with long-term mental health consequences, including suicidality. In an analysis of 5332 HIV-infected individuals who had participated in four antiretroviral treatment trials, receipt of an efavirenz-containing regimen was associated with a twofold increase in suicidality (a combined measure of suicidal ideation, suicide attempts, and completed suicides) compared with regimens that did not contain efavirenz [27]. We do not use efavirenz-based regimens for treatment naïve patients with mental health disorders given the many other available treatment options. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient", section on 'Efavirenz'.)

Testing algorithms to diagnose HIV infection (July 2014)

We agree with new recommendations from the United States Centers for Disease Control and Prevention (CDC) to use a combination assay that detects HIV antigen and antibodies as the initial test for laboratory-based HIV screening and diagnosis for patients two years and older (algorithm 1) [28]. If the initial test is reactive, an HIV-1/HIV-2 differentiation assay should be performed as a confirmatory test. Testing with an antibody-only assay followed by a confirmatory Western blot is no longer recommended. In comparison, the new algorithm is better able to diagnose acute infection when antibody may not yet be detectable (eg, "window period of acute HIV infection") and can provide information as to whether the patient is infected with HIV-1, HIV-2, or both. Reactive rapid antibody tests performed in community-based settings should be confirmed using this new algorithm as well. (See "Screening and diagnostic testing for HIV infection", section on 'Testing algorithm'.)

Timing of antiretroviral initiation in HIV-infected patients with cryptococcal meningitis (July 2014)

HIV-infected individuals with cryptococcal meningitis can develop paradoxical worsening of cryptococcal disease following initiation of antiretroviral therapy (ART) because immune reconstitution can result in a local inflammatory reaction at sites of a pre-existing infection. Thus, the timing of ART initiation must weigh this risk against the potential advantage of early immune recovery in severely immunosuppressed patients. In a randomized trial of 177 HIV-infected patients with cryptococcal meningitis in Uganda and South Africa, mortality was higher when ART was initiated within one or two weeks after starting antifungal therapy compared with five weeks after starting antifungal therapy [29]. Most excess deaths associated with early ART initiation occurred two to five weeks after initiation of antifungal therapy. Based on results from this and other trials, we suggest that initiation of ART be delayed for at least four weeks after antifungal therapy has been started. For patients with access to close medical follow-up and preventative therapy, we typically start ART 10 weeks after the initiation of antifungal therapy to minimize the risks of immune reconstitution inflammatory syndrome (IRIS) and drug interactions. (See "Clinical management and monitoring during antifungal therapy of the HIV-infected patient with cryptococcal meningoencephalitis", section on 'Timing of antiretroviral therapy'.)

Guidelines on pre-exposure prophylaxis for HIV prevention (June 2014)

Pre-exposure prophylaxis (PrEP) with daily use of tenofovir-emtricitabine, a combination antiretroviral agent, can reduce the risk of HIV acquisition in uninfected individuals who are at high risk of infection. In 2014, the US Public Health Service formally released clinical practice guidelines to help providers decide which patients may benefit from PrEP [30]. The guidelines also advise on the evaluation and monitoring of patients who decide to initiate PrEP. To optimize the efficacy of PrEP, they stress the importance of a comprehensive approach to care that includes HIV testing prior to and during treatment, as well as adherence and risk reduction counseling. UpToDate recommendations are largely consistent with these guidelines. (See "Pre-exposure prophylaxis against HIV infection", section on 'Approach to pre-exposure prophylaxis against HIV'.)

IMMUNOCOMPROMISED HOSTS

Effectiveness of prior zoster vaccination in patients receiving chemotherapy (October 2014)

Live vaccines are contraindicated in patients receiving myelosuppressive chemotherapy. It is therefore ideal to give indicated vaccines prior to the initiation of chemotherapy, when feasible. However, there has been some concern that chemotherapy might reduce the protective effect of vaccinations. A cohort study has demonstrated that zoster vaccine administered prior to the oncologic diagnosis remains effective in patients ≥60 years of age who are receiving chemotherapy for a solid tumor [31]. The incidence rate of herpes zoster among the unvaccinated group was almost twice that of the vaccinated group. (See "Immunizations in patients with cancer", section on 'Zoster vaccine'.)

IMMUNIZATIONS

New human papillomavirus (HPV) vaccine targets nine HPV types (December 2014)

Infection with human papillomavirus (HPV) types 16, 18, 31, 33, 45, 52, and 58 is implicated in approximately 90 percent of invasive cervical cancers. The US Food and Drug Administration has approved Gardasil 9, a 9-valent HPV vaccine that targets those seven HPV types in addition to the two types associated with genital warts (6 and 11), for the prevention of HPV-related disease [32]. In an as-yet-unpublished trial that included approximately 14,000 females randomly assigned to receive the 9-valent or quadrivalent HPV vaccine, immune responses with the two vaccines were comparable for the HPV types targeted by both (6, 11, 16, and 18). Additionally, the 9-valent HPV vaccine was 97 percent effective for preventing precancerous and cancerous lesions of the cervix, vagina, and vulva associated with the other targeted HPV types (31, 33, 45, 52, and 58). Safety profiles were overall similar. The 9-valent vaccine is expected to be available in the US in early 2015. (See "Recommendations for the use of human papillomavirus vaccines", section on 'Available vaccines'.)

Circulating influenza A H3N2 viruses in the United States (December 2014)

In December 2014, the CDC released a health advisory stating that more than half of influenza A H3N2 viruses collected and analyzed in the United States in October and November 2014 were antigenically different (drifted) from the H3N2 antigen included in this season's influenza vaccines [33]. Although influenza has been relatively infrequent up to this point in the season, it appears to be increasing, and most isolated influenza viruses have been H3N2 strains. During previous seasons in which influenza A H3N2 viruses have predominated, higher hospitalization and mortality rates have been reported among older people, very young children, and individuals with certain medical conditions. Influenza vaccination is still strongly recommended because it usually provides some cross-protection against drifted viruses and because influenza vaccines protect against other strains. The CDC health advisory was issued to reemphasize the importance of the use of neuraminidase inhibitors (eg, oseltamivir, zanamivir) when indicated for the treatment and prevention of influenza infection as an adjunct to vaccination. (See "Seasonal influenza vaccination in adults", section on 'Drifted H3N2 viruses during the 2014 to 2015 influenza season'.)

FDA approval of a meningococcal serogroup B vaccine (October 2014)

Neisseria meningitidis serogroup B is responsible for approximately one-third of cases of meningococcal disease in the United States and has caused outbreaks on college campuses in the recent past. Previously licensed meningococcal vaccines in the United States do not protect against serogroup B. In October 2014, the US Food and Drug Administration approved a serogroup B meningococcal vaccine (Trumenba) for use in individuals 10 through 25 years of age [34]. The United States Advisory Committee on Immunization Practices has not yet released recommendations for its use. (See "Meningococcal vaccines", section on 'In children and adolescents' and "Meningococcal vaccines", section on 'Group B meningococcus vaccines'.)

Pneumococcal conjugate vaccine in adults ≥65 years of age (September 2014)

The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for many years in the United States for all adults ≥65 years of age. In September 2014, the United States Advisory Committee on Immunization Practices (ACIP) began also recommending the pneumococcal conjugate vaccine (PCV13) for all adults ≥65 years of age [35]. Current recommendations for individuals ≥65 years of age who have not previously received either PCV13 or PPSV23 are to administer PCV13 followed 6 to 12 months later by PPSV23 (algorithm 2). In patients who have already received PPSV23, at least one year should elapse before they are given PCV13.

The ACIP revision was prompted by results from the CAPiTA trial. This randomized placebo-controlled trial, including approximately 85,000 adults ≥65 years of age in the Netherlands, demonstrated the efficacy of PCV13 against vaccine-type pneumococcal pneumonia, vaccine-type nonbacteremic pneumococcal pneumonia, and vaccine-type invasive pneumococcal disease [36]. However, some concern has been raised that since this trial began before PCV13 was used routinely in infants in the Netherlands, it might not answer the question of whether its use in adults is efficacious in countries that routinely vaccinate infants. (See "Pneumococcal vaccination in adults", section on 'Indications'.)

ACIP recommendations for the 2014-2015 influenza season (August 2014)

In August 2014 the United States Advisory Committee on Immunization Practices (ACIP) released updated recommendations for the prevention of seasonal influenza with vaccines [37]. Important changes from previous recommendations include:

A preferential recommendation for the nasal spray vaccine (live attenuated influenza vaccine, LAIV) over the intramuscular injection (inactivated influenza vaccine, IIV) for children two through eight years of age who do not have specific contraindications to the nasal vaccine (eg, asthma, egg allergy, diabetes, immunosuppression). UpToDate agrees with this recommendation, but also prefers LAIV for children older than eight years. If LAIV is not immediately available, IIV should be administered to avoid missing an opportunity for influenza immunization. (See "Seasonal influenza in children: Prevention with vaccines", section on 'LAIV compared with IIV'.)

Changes to the dosing schedule for children six months through eight years of age (algorithm 3). (See "Seasonal influenza in children: Prevention with vaccines", section on 'Schedule'.)

Recommendations for adults are largely unchanged. (See "Seasonal influenza vaccination in adults", section on 'Overview'.)

Efficacy of high-dose influenza vaccine in elderly adults (August 2014)

Due to concern that standard-dose influenza vaccines may be less effective in elderly adults than in younger adults, a high-dose influenza vaccine, Fluzone high-dose, has been developed. In a trial that included more than 30,000 adults ≥65 years of age, Fluzone high-dose was modestly more effective than standard-dose Fluzone [38]. Among individuals in the high-dose group, 1.4 percent had laboratory-confirmed influenza associated with an influenza-like illness compared with 1.9 percent in the standard-dose group (relative efficacy 24.2 percent). The rates of serious adverse events were similar with the high-dose and standard-dose vaccines. For individuals ≥65 years of age, we prefer Fluzone high-dose when available rather than a standard-dose inactivated vaccine. However, the United States Advisory Committee on Immunization Practices has not stated a preference for Fluzone high-dose over the standard-dose inactivated influenza vaccine in older adults [37,39]. (See "Seasonal influenza vaccination in adults", section on 'High-dose vaccine' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation'.)

MYCOBACTERIAL INFECTIONS

Shortened TB treatment with fluoroquinolone-containing regimen not effective (September 2014, MODIFIED October 2014)

Because of their highly bactericidal activity against Mycobacterium tuberculosis, the use of fluoroquinolones in an antituberculous regimen has been hypothesized to allow a shorter duration of treatment. However, shortening treatment with a moxifloxacin-containing regimen to four months was not effective in a phase III trial that included 1931 patients with uncomplicated, smear-positive pulmonary tuberculosis. The study demonstrated that each of two moxifloxacin-containing regimens (isoniazid, rifampin, pyrazinamide, and moxifloxacin; or rifampin, pyrazinamide, ethambutol, and moxifloxacin) given for 17 weeks resulted in greater treatment failure and relapse compared with the standard control regimen of two months of isoniazid, rifampin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampin [40]. This was despite shorter times to negative sputum cultures with the moxifloxacin regimens than the control regimen. Subsequent studies using gatifloxacin as the fluoroquinolone or moxifloxacin in combination with other antituberculous agents similarly demonstrated worse outcomes with a shorter four-month regimen [41,42]. (See "Treatment of pulmonary tuberculosis in HIV-negative patients", section on 'Fluoroquinolones'.)

Corticosteroids of limited benefit in tuberculous pericarditis (September 2014)

Whether corticosteroids are beneficial for patients with tuberculous pericarditis has been controversial. A randomized trial including 1400 adults initiating antimicrobial treatment for definite or probable tuberculous pericarditis in South Africa (approximately two-thirds of patients had concomitant HIV infection) demonstrated no effect of adjunctive corticosteroids on the primary composite efficacy outcome of death, cardiac tamponade requiring pericardiocentesis, or development of constrictive pericarditis [43]. Corticosteroid use did reduce the incidence of constrictive pericarditis alone (4.4 versus 7.8 percent). The overall lack of benefit may have reflected harm from corticosteroid treatment in patients with HIV, and it remains possible that patients without HIV could benefit from corticosteroids. Based on the totality of the evidence, we do not routinely use adjunctive corticosteroids in the absence of constrictive disease or high risk for constrictive disease. This approach is in disagreement with prior guidelines favoring routine use of corticosteroids for all patients with tuberculous pericarditis.

We continue to suggest administration of corticosteroids for patients with constrictive tuberculous pericarditis and for those felt to be at high risk of developing the condition (ie, large effusion, high level of pericardial fluid inflammatory cells, or early signs of constriction). (See "Tuberculous pericarditis", section on 'Role of corticosteroids'.)

VIRAL INFECTIONS, NON-HIV

Direct-acting antiviral agents for post-transplantation hepatitis C recurrence (November 2014)

Recurrence of hepatitis C virus (HCV) following liver transplantation occurs in more than 95 percent of patients who fail to have the virus eradicated prior to transplantation. Current treatment regimens using direct-acting antiviral agents such as sofosbuvir and simeprevir are based largely on studies in patients with HCV who have not undergone liver transplantation. Treatment of patients with HCV recurrence after liver transplantation with direct-acting antiviral agents was recently examined in a study with 34 patients [44]. The patients were given ombitasvir (an NS5A inhibitor), ritonavir-boosted paritaprevir (a protease inhibitor), dasabuvir (a nonnucleoside NS5B polymerase inhibitor), and ribavirin for 24 weeks. A sustained virologic response at 24 weeks was achieved by 97 percent of patients, with no episodes of graft rejection. This study supports the use of direct-acting antiviral agents in patients with HCV recurrence following liver transplantation. (See "Liver transplantation for hepatitis C virus infection", section on 'Other regimens'.)

Ledipasvir-sofosbuvir for genotype 1 chronic hepatitis C infection (December 2013, MODIFIED October 2014)

Interferon-free options for chronic genotype 1 hepatitis C virus (HCV) infection are increasing. A once-daily combination pill of two direct-acting antiviral agents, ledipasvir and sofosbuvir, is becoming available in the United States and elsewhere. In several large open-label trials, ledipasvir-sofosbuvir achieved sustained virologic response (SVR) rates exceeding 90 percent in genotype 1 infected patients regardless of treatment history or presence of cirrhosis [45-47]. For all patients with chronic genotype 1 HCV infection, we favor the regimen of ledipasvir-sofosbuvir because of its efficacy, its favorable adverse effect profile, its ease of administration, and extensive data to support its use. For treatment-naïve patients, treatment duration is eight weeks for those without cirrhosis and a viral level <6 million international units/mL, and 12 weeks for those with cirrhosis or a higher viral level. For treatment-experienced patients, treatment duration is 12 weeks for those without cirrhosis and 24 weeks for those with cirrhosis. (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Selection of treatment regimens'.)

Clusters of enterovirus D68 infections in the United States (September 2014)

Since August 2014, clusters of severe respiratory infections due to enterovirus D68 have been reported across the continental United States [48,49]. These have occurred predominantly in children with a prior history of asthma and have been generally characterized by low grade or absent fever with wheezing, dyspnea, hypoxia, and perihilar infiltrates. Infection has also been associated with rare cases of limb weakness with spinal cord lesions on imaging. The possibility of enterovirus D68 should thus be suspected in cases of severe respiratory illnesses without alternative explanation, particularly in young children. Treatment is supportive and prevention relies on basic hygienic measures, including handwashing with soap and water. Alcohol-based sanitizers may be ineffective against enteroviruses. Enterovirus D68 had previously been implicated in smaller clusters of respiratory infections but was otherwise rarely reported. Additional surveillance information can be found on the CDC website. (See "Virus-induced wheezing and asthma: An overview", section on 'Enterovirus D68 infection' and "Clinical manifestations and diagnosis of enterovirus and parechovirus infections", section on 'Respiratory disease' and "Epidemiology, pathogenesis, treatment, and prevention of enterovirus and parechovirus infections", section on 'Serotypes and disease'.)

Chikungunya fever in the Caribbean and the Americas (July 2014)

Chikungunya is an arthropod-borne virus (arbovirus) endemic to West Africa that causes acute febrile polyarthralgia and arthritis. In December 2013, the first cases of chikungunya fever in the western hemisphere were reported in the Caribbean Island of Saint Martin [50,51]. Since then, local transmission has been confirmed in many countries and territories in the Caribbean, North America, Central America, and South America [50,52-55]. The first two cases of local transmission in the continental United States were reported in Florida in mid-July 2014 [54,55]; local transmission has been reported more widely in Puerto Rico [56]. (See "Chikungunya fever", section on 'Americas'.)

Risk of perinatal transmission of HBV in the United States (June 2014)

Administration of hepatitis B virus (HBV) vaccination and hepatitis B immune globulin (HBIG) to newborns of women with chronic HBV infection significantly reduces the risk of perinatal HBV transmission but does not eradicate it. In an observational study of over 4000 infants born to HBV-infected mothers in the United States between 1997 and 2010, over 95 percent received HBV vaccination and HBIG [57]. Perinatal transmission occurred in 3.40 percent of births to hepatitis B e antigen (HBeAg) positive mothers and 0.04 percent of births to HBeAg negative mothers. Among women whose HBV DNA results and HBeAg status were known, no HBV transmission occurred with a viral load less than 5 x107 IU/mL, regardless of the HBeAg status. (See "Hepatitis B and pregnancy", section on 'HBV DNA level'.)

Screening for Hepatitis B virus infection in the United States (June 2014)

Infection with Hepatitis B virus (HBV) can lead to chronic liver disease and is preventable with vaccination. The US Preventive Services Task Force (USPSTF) has updated its statement on screening for HBV infection in nonpregnant adolescents and adults to recommend that individuals at high-risk for HBV infection be screened if they have not been vaccinated or if they were vaccinated without prior screening [58]. High-risk populations include persons born in regions with a prevalence of HBV ≥2 percent, US–born persons whose parents were born in regions with a prevalence ≥8 percent, injection drug users, men who have sex with men, household contacts of persons with HBV infection, and individuals with HIV infection. Existing guidelines from the Centers for Disease Control and Prevention and the American Association for the Study of Liver Disease also support screening of high-risk individuals in the US. (See "Diagnosis of hepatitis B virus infection", section on 'Who should be tested or screened'.)

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