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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: Jul 2017. | This topic last updated: Aug 10, 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.


Prevention of meningococcal infection in patients receiving eculizumab (August 2017)

Eculizumab is a monoclonal antibody used for treatment of complement-mediated hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria. It has been associated with a 1000 to 2000-fold increased incidence of meningococcal disease, including life-threatening and fatal infection. Therefore, patients should be immunized with meningococcal vaccines (both ACYW135 and serogroup B), if possible, at least two weeks prior to receiving a first dose of eculizumab. However, invasive meningococcal disease has occurred among patients receiving eculizumab despite receipt of meningococcal vaccine, including infections caused by non-typeable strains not included in the vaccines [1]. Accordingly, in addition to vaccination, we suggest daily antimicrobial prophylaxis (penicillin or, for penicillin-allergic patients, a macrolide) for prevention of meningococcal infection in all patients treated with eculizumab. In addition, patients should be monitored for signs of meningococcal infection and evaluated immediately if infection is suspected. (See "Treatment and prevention of meningococcal infection", section on 'Patients receiving eculizumab'.)

Risk of tympanic membrane perforation with topical quinolones after tympanostomy (August 2017)

An observational study reported that treatment with quinolone ear drops after tympanostomy tube (TT) placement was associated with increased risk of tympanic membrane (TM) perforation compared with treatment with neomycin plus hydrocortisone drops [2]. While the study raises concerns regarding the safety of quinolone ear drops, the findings should be viewed as preliminary given the observational design and source of the data (Medicaid encounter and pharmacy billing data). In addition, this study evaluated only the risk of TM perforation and did not address other ototoxicities, which are well-established side effects of neomycin (and other aminoglycosides). Until additional data are available, we continue to suggest fluoroquinolone-containing drops as our preferred treatment for uncomplicated acute TT otorrhea. (See "Tympanostomy tube otorrhea in children: Causes, prevention, and management", section on 'Uncomplicated acute TTO'.)

Antibiotic therapy for skin abscess (July 2017)

Management of skin abscess consists of incision and drainage; the role of antibiotic therapy depends on individual clinical circumstances, including abscess size. In a randomized trial including more than 780 patients with skin abscess ≤5 cm (most were larger than 2 cm) who underwent incision and drainage, higher cure rates were observed among those who received antibiotic therapy with methicillin-resistant Staphylococcus aureus (MRSA) coverage (trimethoprim-sulfamethoxazole or clindamycin) than those who received placebo (82 or 83 percent versus 69 percent); MRSA was isolated in 49 percent of cases [3]. These findings support our approach to management of patients with skin abscess, in which we suggest antibiotic therapy in addition to incision and drainage for patients with skin abscess ≥2 cm. (See "Cellulitis and skin abscess in adults: Treatment", section on 'Role of antibiotic therapy'.)

Delafloxacin for treatment of skin and soft tissue infections (July 2017)

Delafloxacin, a fluoroquinolone, has been approved by the US Food and Drug Administration for treatment of bacterial skin and soft tissue infections. It has activity against staphylococci (including methicillin-resistant strains), gram-negative bacteria (including Pseudomonas aeruginosa and Enterobacteriaceae), and some anaerobes (including Clostridium difficile) but does not have activity against enterococci. In two phase III clinical trials, the drug was statistically noninferior to the combination of vancomycin and aztreonam at the endpoint of early clinical response at 48 to 72 hours [4,5]. Given limited clinical experience with delafloxacin, at this time its use should be reserved for patients who do not respond to or do not tolerate first-line antimicrobial agents. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of skin and soft tissue infections", section on 'Delafloxacin'.)

Increasing incidence of multiply recurrent C. difficile infection (July 2017)

Recurrent C. difficile infection (CDI) is defined by complete abatement of CDI symptoms while on appropriate therapy, followed by subsequent reappearance of symptoms after treatment has been stopped. Patients who have experienced one recurrence of CDI are at significantly increased risk for further recurrences (multiply recurrent CDI or mrCDI). In one retrospective cohort study including more than 45,000 patients with CDI in the United States between 2001 and 2012, the annual incidence of mrCDI nearly doubled (from 0.0107 to 0.0309 cases per 1000 person-years) [6]. Risk factors for mrCDI included age, female sex, nursing home residence, and use of antibiotics, glucocorticoids, or proton-pump inhibitors within 90 days of CDI diagnosis. The increased incidence of mrCDI was independent of known risk factors for CDI, raising the possibility that the biology of CDI is changing. (See "Clostridium difficile in adults: Epidemiology, microbiology, and pathophysiology", section on 'Recurrent infection'.)

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) [7]. 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 [8]. 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 [9]. 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 [10]. 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) [11]. 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'.)


Amphotericin B for the treatment of HIV-infected patients with Talaromyces marneffei (formerly Penicillium marneffei) infection (June 2017)

Talaromyces marneffei (formerly Penicillium marneffei) is an important cause of morbidity and mortality in HIV-infected and other immunosuppressed patients in Southeast Asia. For patients with moderate to severe disease outside the central nervous system, treatment typically includes amphotericin B for two weeks followed by oral itraconazole, but amphotericin B can be difficult to administer because of the need for intravenous access and potential toxicity. Nevertheless, the importance of initial therapy with amphotericin B was highlighted by an open-label randomized trial of 440 patients with end-stage HIV infection (median CD4 count 10 cells/microL) and talaromycosis, in which the mortality rate with amphotericin B for two weeks followed by itraconazole was similar at two weeks but lower at 24 weeks (11 versus 21 percent) compared with itraconazole alone for the duration of therapy [12]. The use of lipid amphotericin preparations may reduce the potential toxicity. (See "Diagnosis and treatment of Talaromyces (Penicillium) marneffei infection", section on 'Patients without central nervous system disease'.)

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 July 2017, in the United States, 98 cases have been reported, with most cases occurring in New York (68 cases) and New Jersey (20 cases) [13,14]. 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 [15]. (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) [16]. 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'.)

New once-daily raltegravir formulation (June 2017)

For patients with HIV infection, the most effective antiretroviral therapy regimens contain two different nucleoside reverse transcriptase inhibitors and an integrase strand transfer inhibitor (INSTI). Raltegravir, the first available INSTI, has traditionally required twice-daily dosing. In the United States, a new raltegravir formulation that allows once-daily dosing (two 600 mg tablets once daily) has recently been approved for treatment-naïve patients [17]. This approval continues to expand the treatment options for patients with newly diagnosed HIV infection, particularly when drug interactions limit the use of other once-daily INSTIs. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient", section on 'Commonly used agents'.)

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 [18]. 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 [19]. 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'.)


Recombinant hemagglutinin influenza vaccine in older adults (June 2017)

Recombinant hemagglutinin influenza vaccines (Flublok and Flublok Quadrivalent) are produced using recombinant DNA technology and a baculovirus expression system rather than the traditional egg-based methods. In a randomized trial that included adults ≥50 years of age, Flublok Quadrivalent was more effective than the quadrivalent standard-dose inactivated vaccine for preventing influenza [20]. Flublok Quadrivalent has not been compared directly with the high-dose inactivated vaccine, which has been found to be more effective than the standard dose inactivated vaccine in older adults (including a mortality benefit). Flublok Quadrivalent is a reasonable alternative to the high-dose vaccine for older adults. (See "Seasonal influenza vaccination in adults", section on 'Recombinant hemagglutinin vaccine'.)

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 [21]. 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 [22]. (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 [23]. 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 [24]. 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 [25,26]. 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'.)


CDC guidelines for prevention of surgical site infection (June 2017)

The Centers for Disease Control published new guidelines for prevention of surgical site infection in May 2017; these update the prior guidelines published in 1999 [27]. The guidelines state that administration of antibiotic prophylaxis should be timed such that a bactericidal concentration is present in tissue at the time of incision, additional antibiotic prophylaxis is not necessary after the surgical incision is closed, and intraoperative skin preparation should be performed with an alcohol-based antiseptic (unless contraindicated). Our recommendations are generally consistent with these guidelines. (See "Overview of control measures for prevention of surgical site infection in adults" and "Antimicrobial prophylaxis for prevention of surgical site infection in adults".)


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 [28]. 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 [29]. 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 [30]. 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 [31]. 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'.)


Updated guidance on diagnosis of Zika virus infection in pregnancy (July 2017)

The Centers for Disease Control and Prevention have updated their guidance for diagnosis of Zika virus infection in asymptomatic pregnant women (algorithm 1) [32]. Two major changes are: (1) for asymptomatic women with possible Zika virus exposure but no ongoing exposure, nucleic acid testing (NAT) is no longer recommended; and (2) for asymptomatic women with ongoing Zika virus exposure, first and second trimester IgM antibody testing is no longer recommended, but NAT should be performed three times during pregnancy. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Asymptomatic women with limited or ongoing risk of Zika virus exposure'.)

Risk of congenital Zika virus syndrome (June 2017)

The magnitude of risk of birth defects resulting from in utero exposure to Zika virus is uncertain. The Centers for Disease Control and Prevention identified over 2500 pregnant women in US territories with Zika virus infection in early 2017 [33]. Maternal Zika virus infection in the first trimester was associated with an 8 percent incidence of offspring with birth defects, but fell to 4 to 5 percent with infection in the second and third trimesters. Because of study limitations, these figures likely understate the true risk of any congenital adverse outcome. Importantly, structural birth defects were seen with similar frequency in infants born to women with and without clinical signs and symptoms of Zika virus infection during pregnancy. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Risk of vertical transmission and anomalies'.)

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 [34].

In a cohort of low-risk patients 66 years and older who presented to their primary care physician with acute upper respiratory infection, 46 percent were treated with an antibiotic, with overprescribing rates highest for patients with acute bronchitis [35]. Physicians who saw high volumes of patients and mid- to late-career physicians were more likely to prescribe antibiotics.

These studies add further support to overuse and lack of benefit for routine use of antibiotics for patients with acute bronchitis. (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 [36]. 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 [37]. (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 [38]. 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 [39]. 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 [40,41]. 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 [42]. 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 2). 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 [43]. 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 [44]. 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 [45]. Over 90 percent of cases reported exposure to poultry, mostly at live poultry markets [46]. Several clusters of cases have been detected, but there has been no evidence of sustained human-to-human transmission [47]. 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 [45]. (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'.)


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 [48]. 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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