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What's new in infectious diseases
Official reprint from UpToDate® ©2017 UpToDate®
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What's new in infectious diseases
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: May 2017. | This topic last updated: Jun 14, 2017.

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.


Treatment of nonpurulent cellulitis (June 2017)

Empiric antibiotic therapy for nonpurulent cellulitis (ie, with no purulent drainage and no associated abscess) should be active against beta-hemolytic streptococci and methicillin-susceptible Staphylococcus aureus (MSSA) but not necessarily methicillin-resistant S. aureus (MRSA). This approach is supported by a randomized trial of nearly 500 patients with nonpurulent cellulitis, in which cephalexin plus placebo (active against beta-hemolytic streptococci and MSSA) and cephalexin plus trimethoprim-sulfamethoxazole (TMP-SMX, which adds activity against MRSA) resulted in statistically similar clinical cure rates (69 versus 76 percent) [1]. Although there was a trend toward higher cure rates with the addition of TMP-SMX, the results were likely skewed by a relatively large number of patients who did not complete the full course of therapy. (See "Cellulitis and skin abscess in adults: Treatment", section on 'Cellulitis'.)

Decreased susceptibility to fluoroquinolones in Shigella infection (April 2017)

When treatment for Shigella infection is indicated, susceptibility testing should be performed to guide antimicrobial selection. In the United States, an increasing proportion of Shigella isolates have minimum inhibitory concentrations (MIC) to ciprofloxacin of 0.12 to 1 mcg/mL [2]. Although these MIC values are considered susceptible and their impact on treatment outcomes in Shigella is unknown, they are associated with resistance genes that result in worse outcomes with fluoroquinolone treatment in other Enterobacteriaceae. Clinicians should request the MIC to ciprofloxacin if it is not provided with susceptibility results and avoid fluoroquinolones if the MIC is ≥0.12 mcg/mL. (See "Shigella infection: Clinical manifestations and diagnosis", section on 'Susceptibility testing' and "Shigella infection: Treatment and prevention in adults", section on 'Antibiotic selection'.)

IDSA guidelines on healthcare-associated ventriculitis and meningitis (April 2017)

The Infectious Diseases Society of America published new guidelines related to healthcare-associated ventriculitis and meningitis in March 2017 [3]. They provide guidance for clinicians on the clinical manifestations, diagnosis, treatment, and prevention of ventriculitis and meningitis in patients with central nervous system hardware, with a focus on cerebrospinal fluid shunts and drains, and in patients who have had neurosurgery or head trauma. Main concepts include the need for a low threshold of suspicion given the potentially subtle clinical findings of these infections and the importance of selecting an antimicrobial regimen that has bactericidal activity and achieves adequate concentrations in the cerebrospinal fluid. Our recommendations are generally consistent with these guidelines. (See "Infections of cerebrospinal fluid shunts and other devices", section on 'Treatment' and "Initial therapy and prognosis of bacterial meningitis in adults", section on 'Healthcare-associated meningitis' and "Gram-negative bacillary meningitis: Treatment".)

E. coli O157:H7 outbreak associated with soy nut butter (March 2017)

Escherichia coli O157:H7, which causes bloody diarrhea and is associated with the hemolytic-uremic syndrome, is typically transmitted through contaminated beef products and produce, but other foods have also been implicated in outbreaks. In the United States, a particular brand of soy nut butter (I.M. Healthy) has been linked to a multistate E. coli O157:H7 outbreak that has affected mainly children [4]. Although the soy nut butter products have been recalled, individuals should be advised to avoid and discard any remaining product, and the possibility of E. coli O157:H7 infection should be considered in exposed patients with diarrheal illnesses. Details on the outbreak can be found on the Centers for Disease Control and Prevention website. (See "Microbiology, pathogenesis, epidemiology, and prevention of enterohemorrhagic Escherichia coli (EHEC)", section on 'Other foods'.)

Bezlotoxumab for secondary prevention of C. difficile infection (February 2017)

Bezlotoxumab is a monoclonal antibody against Clostridium difficile toxin B (which is essential for the virulence of the organism) that received US Food and Drug Administration approval in 2016 for secondary prevention of C. difficile infection in patients at high risk for recurrence. In two randomized trials including more than 2500 patients with C. difficile infection, the addition of bezlotoxumab to standard oral antibiotic therapy lowered the rate of recurrence (16 to 17 versus 26 to 28 percent with antibiotics alone) [5]. However, further evaluation to identify those who would be most likely to benefit is needed to define the optimal role of bezlotoxumab relative to other approaches to C. difficile infection treatment, including fecal microbiota transplant. (See "Clostridium difficile in adults: Treatment", section on 'Alternative therapies'.)


Healthcare-associated Candida auris infections in the United States (June 2017)

The emergence of a multidrug-resistant Candida species, Candida auris, was first reported from the United States and United Kingdom in 2016. It has been detected in over a dozen countries on five continents and has been associated with healthcare-associated outbreaks. As of May 2017, in the United States, 77 cases have been reported, with most cases occurring in New York (53 cases) and New Jersey (16 cases) [6]. The most common site of infection has been the bloodstream. Nearly all patients have had multiple underlying conditions and exposure to healthcare facilities. An echinocandin (anidulafungin, caspofungin, or micafungin) is the treatment of choice for C. auris infection [7]. (See "Epidemiology and pathogenesis of candidemia in adults", section on 'Emergence of C. auris' and "Treatment of candidemia and invasive candidiasis in adults", section on 'C. auris'.)


Feasibility of test and treat strategy for HIV in Africa (June 2017)

Several community-based trials in Africa have been launched to evaluate whether a "test and treat" strategy can decrease HIV transmission in those areas. In an observational analysis of one of those trials from Uganda and Kenya, initiation of annual HIV screening and immediate linkage to care for antiretroviral therapy (ART) among a cohort of over 75,000 residents was associated with increases in the proportion of the HIV-infected individuals who were diagnosed (from 65 percent at baseline to 96 percent two years later), the proportion of diagnosed patients who initiated ART (80 to 93 percent), and the proportion of the total HIV-infected population who achieved viral suppression (45 to 80 percent) [8]. These results support the feasibility of a "test and treat" strategy, but the impact on HIV incidence within those communities is yet to be determined. (See "HIV infection: Risk factors and prevention strategies", section on 'Test and treat'.)

HIV transmission with drug-resistant virus despite pre-exposure prophylaxis (February 2017)

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) is an effective intervention to reduce HIV transmission. However, a case report of a patient who acquired a highly drug-resistant HIV strain despite being adherent to PrEP highlights the rare risk of PrEP failure because of transmitted drug resistance [9]. If a patient has had a known exposure to multidrug-resistant HIV, a post-exposure prophylaxis regimen containing antiretrovirals active against the resistant virus should be initiated, even if the patient had been using PrEP. (See "Pre-exposure prophylaxis against HIV infection", section on 'Drug resistance'.)


Updated guidelines for empiric antifungal therapy for children with fever and neutropenia (June 2017)

Updated guidelines from the International Pediatric Fever and Neutropenia Guideline Panel consider children with cancer or hematopoietic cell transplant as high risk for invasive fungal infection if they have acute myelogenous leukemia, high-risk acute lymphoblastic leukemia, relapsed acute leukemia, neutropenia for >10 days, or are receiving high-dose corticosteroids [10]. In contrast to the previous guideline, they weakly recommend against initiating empiric antifungal therapy for low-risk patients, using serial galactomannan to guide antifungal therapy, and obtaining computed tomography images of the sinuses before initiating antifungal therapy unless the patient has localizing signs or symptoms. They also now suggest abdominal imaging before initiation of antifungal therapy in high-risk patients. (See "Fever in children with chemotherapy-induced neutropenia", section on 'Antifungal therapy'.)

Ibrutinib and Pneumocystis pneumonia (December 2016)

The Bruton tyrosine kinase inhibitor ibrutinib has not clearly been associated with an increased risk of opportunistic infections, but cases have been reported. In a series of 96 patients receiving ibrutinib as the sole agent for chronic lymphocytic leukemia (CLL), five were reported to have Pneumocystis pneumonia [11]. All of the infections were grade ≤2 and resolved with oral trimethoprim-sulfamethoxazole. A limitation is that the diagnoses were made by polymerase chain reaction (PCR) of bronchoalveolar lavage fluid, which could represent a false positive in the setting of colonization with Pneumocystis. Nevertheless, clinicians should have a high index of suspicion for Pneumocystis pneumonia in patients receiving ibrutinib, and the diagnosis should be sought in those with compatible signs and symptoms. (See "Risk of infections in patients with chronic lymphocytic leukemia", section on 'Ibrutinib' and "Prevention of infections in patients with chronic lymphocytic leukemia", section on 'Ibrutinib and idelalisib'.)


Missed opportunity for MMR vaccination during pretravel consultation (May 2017)

Measles is a highly contagious viral illness spread by respiratory droplets; complications include pneumonia, otitis media, and encephalitis. Travelers are at risk for measles infection, and measles, mumps, and rubella (MMR) vaccination is recommended for all international travelers without evidence of immunity. However, in a retrospective review including more than 6600 adults who visited a United States pretravel clinic and were eligible for MMR vaccine, fewer than half of these individuals received it during the consultation [12]. The pretravel visit provides an important opportunity to reduce the likelihood of importation and transmission of measles by ensuring that MMR vaccination (in addition to other routine immunizations) is current. (See "Immunizations for travel", section on 'Measles, mumps, and rubella'.)

Maternal Tdap vaccination and prevention of infant pertussis (May 2017)

Immunization with the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended for women during each pregnancy in order to provide passive protection against pertussis to their infants. Although passive transfer of maternal antibodies can blunt the infant's own immune response to infant doses of the diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccine, it does not appear to interfere with clinical vaccine efficacy. In a retrospective study of nearly 150,000 infants at every level of DTaP vaccine exposure, infants exposed in utero to Tdap vaccine were better protected against pertussis during the first year of life than infants not exposed in utero [13]. (See "Immunizations during pregnancy", section on 'Rationale, efficacy, and safety'.)

Pregnancy outcomes with HPV vaccination (March 2017)

Human papillomavirus (HPV) vaccination during pregnancy is not recommended, but mounting evidence suggests that it is safe. In a large cohort study from Denmark, the risks of spontaneous abortion, major birth defects, preterm birth, and low birth weight were comparable among women who received quadrivalent HPV vaccine during pregnancy (mostly during the first trimester) and matched controls who did not [14]. Women who inadvertently receive HPV vaccine during pregnancy can be reassured that it does not increase their risk of adverse pregnancy or fetal outcomes. (See "Immunizations during pregnancy", section on 'Human papillomavirus'.)

High-dose influenza vaccine in older adults (March 2017)

For influenza vaccination of adults ≥65 years of age, we recommend the high-dose inactivated influenza vaccine, which has previously been shown to be more immunogenic and modestly more effective at preventing influenza infection than the standard-dose vaccine. In a study of United States Medicare beneficiaries ≥65 years of age, the high-dose vaccine was more effective than the standard-dose vaccine for preventing postinfluenza death during the 2012-2013 influenza season, a season when circulation of H3N2 influenza A (a strain associated with severe disease) was common [15]. In contrast, it was not more effective for preventing postinfluenza death during the following season, when H1N1 influenza A (a strain associated with mild disease) predominated. This difference was likely due to the difficulty in demonstrating benefit during a mild influenza season, when death is a rare outcome. The high-dose vaccine was associated with a reduced risk of hospitalization during both seasons. (See "Seasonal influenza vaccination in adults", section on 'High-dose vaccine'.)

Recommended immunization schedule—United States, 2017 (March 2017)

The Advisory Committee on Immunization Practices has released the 2017 recommended immunization schedule for children and adolescents in the United States [16,17]. New recommendations include the following:

All infants should now receive monovalent hepatitis B vaccine within 24 hours of birth; earlier recommendations allowed some infants born to hepatitis B surface antigen-negative mothers to receive the vaccine after discharge. (See "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Mother's HBsAg status unknown, birth weight ≥2 kg'.)

When administered during pregnancy, the tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine should be given as early as possible between 27 and 36 weeks of gestation. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination'.)

For individuals receiving the meningococcal serogroup B vaccine MenBFHbp (Trumenba), two doses are recommended for healthy adolescents and young adults who are not at increased risk for meningococcal disease. Three doses are recommended for individuals ≥10 years of age at increased risk for meningococcal disease and for use during serogroup B meningococcal disease outbreaks (table 1). Previously, three doses were recommended for all recipients. The dosing frequency and interval for the other serogroup B vaccine, MenB-4C (Bexsero), have not changed. (See "Meningococcal vaccines", section on 'Serogroup B meningococcus vaccines'.)


Ultraviolet environmental disinfection and in-hospital transmission of resistant organisms (January 2017)

Ultraviolet (UV) radiation may be a useful adjunctive tool for surface disinfection to reduce in-hospital transmission of multidrug-resistant organisms. One cluster-randomized crossover study evaluated the addition of UV light to standard disinfection alone (quaternary ammonium for methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci or multidrug-resistant Acinetobacter, and bleach for Clostridium difficile) for rooms from which a patient on contact precautions for these pathogens was discharged [18]. Among over 20,000 patients subsequently admitted to these rooms, UV light reduced the overall incidence of colonization or infection with these pathogens by 30 percent, but it did not substantially reduce the individual incidence of C. difficile infection. (See "Infection prevention: General principles", section on 'Healthcare environment: Cleaning and disinfection'.)


Role of person-to-person transmission in extensively drug-resistant tuberculosis (XDR-TB) (January 2017)

It has been postulated that extensively drug-resistant tuberculosis (XDR-TB) is acquired mainly as the result of inadequate treatment. However, in a study of 400 South African patients with XDR-TB, 69 percent had not received prior treatment for multidrug-resistant TB, and genotypic analysis demonstrated that over 80 percent of isolates belonged to one of several defined phylogenetic clusters, suggesting person-to-person transmission in the majority of cases [19]. These findings imply that focus on interrupting transmission (both community-based and health care facility-based) is paramount to limiting spread of complex drug-resistant TB strains. (See "Epidemiology of extensively drug-resistant tuberculosis", section on 'South Africa'.)

Guidelines on diagnosis of tuberculosis (January 2017)

Guidelines from the American Thoracic Society, Infectious Diseases Society of America, and the Centers for Disease Control and Prevention on the diagnosis of tuberculosis in adults and children were published in December 2016 [20]. They state that an interferon-gamma release assay (IGRA) is generally preferred for diagnosis of latent tuberculosis infection (LTBI) in individuals five years or older who have low-to-intermediate risk of progression to active disease (table 2), although the tuberculin skin test (TST) is an acceptable alternative if IGRA is not available or too costly. For those who have high risk of progression to active disease, either IGRA or TST is acceptable, but many guideline panel members noted using the alternative test if the initial one was negative and considering a positive result from either test to indicate LTBI. The evaluation of suspected tuberculosis disease should include three sputum specimens for acid-fast bacilli (AFB) smear and culture and one or more specimens for nucleic acid amplification (NAA) testing. (See "Diagnosis of latent tuberculosis infection (tuberculosis screening) in HIV-uninfected adults" and "Diagnosis of pulmonary tuberculosis in HIV-uninfected adults" and "Latent tuberculosis infection in children" and "Tuberculosis disease in children".)


Guidelines on diagnosis and treatment of leishmaniasis (January 2017)

Guidelines on the management of leishmaniasis in North America were published by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH) in December 2016 [21]. They emphasize use of multiple diagnostic tools to maximize diagnostic likelihood and submission of relevant specimens to a reference laboratory for parasite species identification. For suspected cutaneous leishmaniasis (CL), a full-thickness skin biopsy from a clean, active-appearing ulcer is recommended; for patients with mucocutaneous leishmaniasis (ML), biopsy specimens should be obtained by an otolaryngologist. For suspected visceral leishmaniasis (VL), bone marrow aspirate is the preferred sample; in addition, serum should be tested for antileishmanial antibodies. The treatment approach to CL depends on several factors, including the extent of disease, the infecting parasite species, and the presence of immunocompromising conditions. For VL, liposomal amphotericin B is the preferred treatment; miltefosine, pentavalent antimonials, and other forms of amphotericin are alternatives. (See "Cutaneous leishmaniasis: Clinical manifestations and diagnosis" and "Cutaneous leishmaniasis: Treatment" and "Visceral leishmaniasis: Clinical manifestations and diagnosis" and "Visceral leishmaniasis: Treatment".)


IUD use does not impact human papillomavirus infection (March 2017)

A reduction in cervical cancer rates among intrauterine device (IUD) users has been observed and attributed to favorable effects of the device on human papillomavirus (HPV) clearance. However, a prospective cohort study that controlled for sexual and behavioral confounders reported no difference in HPV acquisition or clearance among women and girls with or without an IUD [22]. Thus, IUD use does not appear to impact HPV infection. (See "Intrauterine contraception: Devices, candidates, and selection", section on 'IUDs cause infection'.)

Postexposure prophylaxis of bacterial sexually transmitted infections (March 2017)

Given the high incidence of bacterial sexually transmitted infections, novel preventive strategies are warranted, particularly for high-risk individuals. In an open-label randomized trial of approximately 200 men who have sex with men (MSM), taking doxycycline within 72 hours of condomless sexual exposures reduced the incidence of chlamydia and syphilis [23]. There was no effect on gonorrhea rates, likely because of the prevalence of tetracycline resistance. Although an intriguing strategy, postexposure prophylaxis against bacterial STIs remains experimental until the long-term effects, including the impact on resistance rates, are known. (See "Prevention of sexually transmitted infections", section on 'For high-risk individuals'.)


Evaluation of new testing algorithms for early Lyme disease (March 2017)

Only 30 percent of patients with early localized Lyme disease (erythema migrans) are seropositive at the time of presentation using the conventional two-tier testing method (a whole cell lysate enzyme immunoassay [EIA] followed by a Western blot). Several modified algorithms using a combination of different immunoassays have been proposed to improve detection of early disease and eliminate the need for Western blot testing, which can be difficult to perform and interpret. In a study evaluating several such algorithms, they were more sensitive than the conventional method (36 to 54 versus 25 percent); all approaches had similar specificity [24]. Although sequential immunoassay testing is not cleared by the US Food and Drug Administration (FDA) for Lyme diagnosis, these algorithms may be useful future tools for the diagnosis of early disease. (See "Diagnosis of Lyme disease", section on 'Algorithms using two enzyme immunoassays'.)

Autoimmune hemolytic anemia after recovery from babesiosis (March 2017)

Babesiosis is known to cause hemolysis from direct parasite-mediated lysis of red blood cells in the circulation. A new association of Babesia infection with autoimmune (autoantibody-mediated) hemolytic anemia (AIHA) has been reported [25]. In a series of 86 patients treated for Babesia, 7 percent developed this complication. AIHA was diagnosed two to four weeks after recovery from the infection and was restricted to individuals who were asplenic due to a prior splenectomy. (See "Warm autoimmune hemolytic anemia: Clinical features and diagnosis", section on 'Underlying causes'.)

Screening donated blood for babesiosis in the United States (December 2016)

Naturally occurring Babesia microti infection within the United States is regionally distributed, with high-risk areas located in the Northeast and upper Midwest. In an analysis of almost 90,000 blood donations from four states in these regions, 335 (0.38 percent) were found to be positive for B. microti using a DNA-based or antibody-based test [26]. Screening of donated units was found to be effective in preventing transmission. Testing blood donations for B. microti is not mandatory in the US, but many units collected in high-risk regions are being screened. (See "Blood donor screening: Laboratory testing", section on 'Babesia microti'.)


Respiratory tract infections and antibiotic overuse (June 2017)

Upper respiratory tract infection (URI) and acute bronchitis are among the most common reasons for antibiotic overprescription, and reducing use for these indications is a global health care priority. A prospective cohort study assessing over 28,000 adults with acute cough lasting <3 weeks without radiographic evidence of pneumonia found no difference in rates of major complications, including hospital admission and death, when comparing patients given immediate antibiotic prescriptions with delayed prescription or no prescription [27]. This study adds further support for the lack of benefit for routine use of antibiotics for patients with acute bronchitis and can be used to reassure patients that they are not more likely to develop complications if they are not treated with antibiotics. (See "Acute bronchitis in adults", section on 'Avoiding antibiotic overuse'.)

Future options for HCV-infected patients who have failed DAA regimens (June 2017)

Patients with chronic hepatitis C virus (HCV) infection who have failed treatment with all-oral direct-acting antiviral (DAA) regimens have limited options for retreatment, but regimens in the late stages of development are expected to be effective. In two trials involving over 600 patients with genotypes 1 through 6 infection who had failed either an NS5A inhibitor-containing regimen or a non-NS5A-inhibitor DAA regimen, 12 weeks of sofosbuvir-velpatasvir-voxilaprevir (the last of which is a novel protease inhibitor) resulted in sustained virologic response (SVR) rates of 96 and 98 percent, respectively [28]. Glecaprevir-pibrentasvir, a novel pangenotypic combination of a protease inhibitor and an NS5A inhibitor, also resulted in high SVR rates for genotype 1 infection with prior NS5A exposure [29]. (See "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults", section on 'Prior failure of sofosbuvir-based regimens' and "Treatment regimens for chronic hepatitis C virus genotypes 4, 5, and 6 infection in adults", section on 'Prior failure of direct-acting antiviral regimens' and "Treatment regimens for chronic hepatitis C virus genotype 1 infection in adults", section on 'Prior failure with an NS5A-inhibitor regimen'.)

Rising rates of HCV infection in young women in the United States (May 2017)

In parallel with the opioid and injection drug use epidemic in the United States, rates of hepatitis C virus (HCV) infection have been increasing over the past decade. In particular, the annual number of acute HCV cases among women aged 15 to 44 years rose 3.6-fold from 2006 to 2014 [30]. An estimated 29,000 women with HCV infection gave birth each year between 2011 and 2014; since the risk of vertical transmission is approximately 5.8 percent, this implies that an estimated 1700 infants were infected annually during this time. These numbers highlight the importance of screening at-risk individuals and arranging follow-up for those with HCV infection. (See "Vertical transmission of hepatitis C virus", section on 'Incidence' and "Hepatitis C virus infection in children", section on 'Epidemiology'.)

Investigational low-cost, heat-stable rotavirus vaccine for infants (May 2017)

Rotavirus gastroenteritis is an important cause of mortality in children younger than five years. Although effective vaccines are available, cost and need for refrigeration have limited vaccine uptake. Bovine rotavirus pentavalent vaccine (BRV-PV) is an investigational live, oral, heat-stable vaccine that is administered to infants at 6, 10, and 14 weeks of age. In a placebo-controlled randomized trial in more than 3500 Nigerien infants, BRV-PV was 67 percent efficacious in preventing laboratory-confirmed severe rotavirus gastroenteritis [31]. BRV-PV is less expensive than currently licensed vaccines and holds promise for vaccination programs in areas where cold-chain capacity is limited. (See "Rotavirus vaccines for infants", section on 'Other vaccines'.)

Ebola virus outbreak in the Democratic Republic of the Congo (May 2017)

Ebola virus is among the most virulent pathogens in humans and has resulted in outbreaks in Central Africa, the Sudan, and West Africa. Since 1976 there have been eight outbreaks of Ebola virus in the Democratic Republic of the Congo (DRC). The most recent was reported in May of 2017 [32,33]. Information about this outbreak can be found on the World Health Organization website. The outbreak in the DRC prior to this occurred in 2014 and was quickly contained. (See "Epidemiology and pathogenesis of Ebola virus disease", section on 'Outbreaks in the Democratic Republic of the Congo'.)

HBV reactivation during HCV antiviral therapy (May 2017)

Reactivation of hepatitis B virus (HBV) can occur during direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection. Among 29 cases reported to the US Food and Drug Administration (FDA) or described in the literature between 2013 and 2016, reactivation occurred at an average of 53 days into DAA treatment and was not associated with a particular HCV genotype or DAA regimen [34]. Two cases were fatal, and one patient required liver transplant. Patients should be tested for HBV coinfection prior to initiation of HCV therapy, with HBV treatment initiated for those who meet criteria (table 3). HBV coinfected patients who do not initially meet HBV treatment criteria should be monitored for reactivation during HCV treatment. (See "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection", section on 'HBV coinfection' and "Overview of the management of chronic hepatitis C virus infection", section on 'Monitoring during antiviral therapy'.)

High-dose IV zanamivir does not improve outcomes for severe influenza (February 2017)

There has been interest in determining whether doubling the dose of a neuraminidase inhibitor improves outcomes for severe influenza. Previous studies have not demonstrated a benefit to doubling the dose of oral oseltamivir. An intravenous (IV) formulation of zanamivir has been developed but remains investigational. In a trial, patients with severe influenza were randomly assigned to receive the standard dose of either oral oseltamivir (75 mg twice daily) or IV zanamivir (300 mg twice daily) or a double dose of IV zanamivir (600 mg twice daily) for 5 to 10 days [35]. The time to clinical response (a composite of vital sign stabilization and hospital discharge) was similar in all three groups. (See "Treatment of seasonal influenza in adults", section on 'Dosing'.)

Duration of Zika virus detection in body fluids (February 2017)

The duration of detectable Zika virus RNA varies in different body fluids. In a prospective cohort study including 150 newly infected patients in Puerto Rico, the median and 95th percentiles for time to loss of Zika RNA detection in serum were 14 and 54 days, respectively; the median and 95th percentile values for time to loss of Zika RNA detection in semen were 34 and 81 days, respectively [36]. These data suggest that the likelihood of intrauterine transmission is low in infected women who defer conception for at least eight weeks from the time of exposure, and that the likelihood of sexual transmission is low from infected men who defer unprotected sex for at least six months from the time of exposure. The guidance issued by the United States Centers for Disease Control for prevention of transmission of Zika virus infection is supported by these data. (See "Zika virus infection: An overview", section on 'Transmission'.)

Avian influenza H7N9 in China (February 2017)

A novel avian influenza A H7N9 virus emerged in China in 2013 and caused a wave of cases in humans with a mortality rate of approximately 40 percent. Additional waves have occurred during influenza seasons since then. The fifth wave in late 2016 and early 2017 has been the largest, involving more than 450 cases [37]. Over 90 percent of cases reported exposure to poultry, mostly at live poultry markets [38]. Several clusters of cases have been detected, but there has been no evidence of sustained human-to-human transmission [39]. Of the H7N9 viruses analyzed to date, 7 to 9 percent have had mutations in the neuraminidase gene that confer reduced susceptibility to neuraminidase inhibitors [37]. (See "Avian influenza A H7N9: Epidemiology, clinical manifestations, and diagnosis", section on 'Case counts' and "Avian influenza A H7N9: Treatment and prevention", section on 'Neuraminidase inhibitor resistance'.)

Outbreak of Seoul virus in rat handlers in the United States (January 2017)

In December 2016, a rat breeder in Wisconsin developed an acute febrile illness and was found to be infected with Seoul virus, a type of hantavirus that can cause hemorrhagic fever with renal syndrome [40]. An outbreak investigation revealed additional infections in rat breeders and rats at the facilities in Wisconsin and Illinois that supplied the index patient's rats. States that have received potentially infected rats include Alabama, Arkansas, Colorado, Illinois, Indiana, Louisiana, Michigan, Minnesota, South Carolina, Tennessee, Utah, and Wisconsin. Recommendations for testing potentially exposed individuals and other information can be found on the United States Centers for Disease Control and Prevention’s website. (See "Epidemiology and diagnosis of hantavirus infections", section on 'Outbreaks'.)

Risk of birth defects with Zika virus infection during pregnancy (January 2017)

The risk of birth defects resulting from in utero exposure to Zika virus was 10 and 42 percent in two recent reports [41,42]. The wide range likely reflects differences in study design, populations studied, maternal Zika case definition, and the range of clinical abnormalities included. The most common fetal/newborn findings in these reports were abnormal brain imaging, microcephaly, small size for gestational age, and abnormal neurologic examination. The greatest risk of serious sequelae in offspring appeared to be with first or second trimester infection, but serious sequelae also occurred with third trimester infection. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Risk of vertical transmission and anomalies' and "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate", section on 'Clinical findings'.)

No role for routine serologic screening for genital herpes infection (December 2016)

Genital herpes, which can be caused by herpes simplex virus type 1 or 2 (HSV-1 or HSV-2), is one of the most common sexually transmitted infections, and sexual transmission can occur even in the absence of symptoms. Despite this, routine serologic screening for herpes simplex is not recommended in asymptomatic adolescents and adults due to significant limitations of available tests, as highlighted in a recent US Preventive Services Task Force statement [43]. Limitations include the low specificity and high false positive rate of serologic tests for HSV-2 and the inability of serologic tests for HSV-1 to differentiate oral from genital infection. Furthermore, there are no specific treatment interventions for asymptomatic patients, so the anxiety and disruption of personal relationships associated with a positive test outweigh any potential benefits. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Screening'.)

Prevention of graft reinfection in HCV-infected patients undergoing liver transplantation (December 2016)

In the absence of viral suppression or clearance of chronic hepatitis C virus (HCV) in patients who undergo liver transplantation, the new liver is almost always reinfected. In an open-label study, 16 HCV genotype 1-infected patients undergoing their first liver transplantation from an uninfected donor received a single dose of ledipasvir-sofosbuvir the day they arrived at the hospital for transplantation and once daily for four weeks postoperatively [44]. The sustained virologic response rate 12 weeks after completion of treatment was 88 percent, suggesting that an abbreviated perioperative course of direct-acting antiviral (DAA) treatment can prevent reinfection of the graft. Additional studies are warranted to confirm the efficacy and safety of this approach in other HCV-infected populations and with other DAA regimens. (See "Recurrence of hepatitis C virus infection following liver transplantation", section on 'Perioperative therapy'.)


2016 sepsis guidelines (March 2017)

Updated sepsis guidelines were issued by the Surviving Sepsis Campaign/Society of Critical Care Medicine/European Society of Intensive Care Medicine [45]. Major differences, compared with the 2012 iteration, include: the administration of intravenous antibiotics within one hour of presentation, with emphasis on source control and antibiotic stewardship; infusion of crystalloid solution at a rate at 30 mL/kg/hour within three hours for early fluid resuscitation; and movement away from previously recommended early goal-directed therapy targets (eg, central venous pressure) to use of dynamic predictors of fluid responsiveness, when feasible. Norepinephrine remains the vasopressor of first choice. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Hemodynamic'.)

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