Elinor L Baron, MD, DTMH
Allyson Bloom, MD
Anna R Thorner, MD
Jennifer Mitty, MD, MPH
Sheila Bond, MD
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.
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.
Transmission of Shiga toxin-producing E. coli through raw flour (December 2017)
Ingestion of contaminated beef is the primary means of Shiga toxin-producing Escherichia coli (STEC) transmission, but other foods contaminated with cattle or deer feces can also be sources of infection. A 2016 multistate outbreak of STEC in the United States was traced to a flour production facility when a case-control evaluation identified consumption of raw flour and raw homemade dough as risk factors for infection . This outbreak highlights the variety of food potentially contaminated with STEC and the importance of food safety (eg, not eating raw dough) in preventing infection. (See "Microbiology, pathogenesis, epidemiology, and prevention of enterohemorrhagic Escherichia coli (EHEC)", section on 'Other foods'.)
Pneumonic plague outbreak in Madagascar (October 2017)
Plague is endemic in Madagascar, where cases of bubonic plague occur almost yearly, mainly between September and April. An ongoing outbreak that started in the fall of 2017 is notable for the high number of pneumonic plague cases and for affecting major urban centers, including the capital city . Cases typically occur in more remote, less populated rural regions. The risk of infection for international travelers to Madagascar remains low; avoiding crowded areas, contact with dead animals or infected tissue, and close contact with patients with known pneumonic plague is advised. Further details on this outbreak can be found on the World Health Organization and Centers for Disease Control and Prevention websites. (See "Epidemiology, microbiology and pathogenesis of plague (Yersinia pestis infection)", section on 'Geographic distribution' and "Clinical manifestations, diagnosis, and treatment of plague (Yersinia pestis infection)", section on 'Prevention'.)
Cholera epidemic in Yemen (August 2017)
Breakdowns in safe water, hygiene, and health services can contribute to epidemic transmission of cholera. In Yemen, where cholera is endemic and the public health infrastructure has been devastated by years of warfare, two rapidly sequential epidemics occurred at the end of 2016 and the middle of 2017. The second of these outbreaks amounts to the world's worst cholera outbreak to date, with approximately 500,000 cases of suspected cholera and 2000 associated fatalities recorded within only four months . (See "Overview of cholera", section on 'Endemic versus epidemic infection'.)
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 . 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, with or without added topical corticosteroids, after tympanostomy tube (TT) placement was associated with increased risk of tympanic membrane (TM) perforation compared with treatment with neomycin plus hydrocortisone drops . 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 adverse effects, including ototoxicity, which is a well-established side effect 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 . 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 [7,8]. 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) . 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) . 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'.)
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 . 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 October 2017, in the United States, more than 160 cases have been reported from 10 states, with most cases occurring in New York and New Jersey . 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 . (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'.)
Elvitegravir-cobicistat use during pregnancy (November 2017)
Preferred antiretroviral regimens for pregnant women differ somewhat from those for the general HIV-infected adult population, in part because of altered pharmacokinetics during pregnancy. Recently updated Department of Health and Human Services perinatal guidelines now state that elvitegravir-cobicistat should not be selected as part of an initial antiretroviral regimen for treatment-naïve pregnant women because of emerging data suggesting decreased drug levels during pregnancy and an associated risk of loss of virologic suppression [14,15]. Furthermore, if an HIV-infected woman is already receiving a suppressive elvitegravir-cobicistat-containing regimen when she becomes pregnant, we suggest switching to a different regimen; if elvitegravir-cobicistat is continued, the potential risks and need for close viral monitoring should be discussed. (See "Antiretroviral and intrapartum management of pregnant HIV-infected women and their infants in resource-rich settings", section on 'On ART with viral suppression'.)
Pre-exposure prophylaxis for HIV in adolescent men who have sex with men (September 2017)
For adults at high risk for acquiring HIV, consistent use of daily tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) can reduce the risk of acquiring HIV by greater than 90 percent. In the United States, TDF-FTC for pre-exposure prophylaxis (PrEP) is approved only for patients over 18 years of age; however, young men who have sex with men (MSM) are at particularly high risk of acquiring HIV. The Adolescent Trials Network studied daily TDF-FTC for PrEP in MSM aged 15 to 17 years; it was well tolerated among those who took their medications, but adherence was suboptimal . Thus, clinicians using PrEP for this vulnerable population should closely assess adherence and promptly address potential barriers (eg, depression, active substance use, stigma). (See "Patient evaluation and selection for HIV pre-exposure prophylaxis", section on 'Adolescents'.)
Safety of tenofovir disoproxil fumarate during pregnancy (September 2017)
For HIV-infected pregnant women, tenofovir disoproxil fumarate (TDF) is a preferred agent to use as part of combination antiretroviral therapy (ART) in both resource-rich and limited settings. A recent meta-analysis reported that TDF increased neonatal mortality, and an accompanying British Medical Journal clinical practice guideline thus suggested zidovudine rather than TDF for HIV-infected pregnant women [17,18]. This conclusion was based on a single trial from Africa in which TDF-based ART resulted in higher rates of very preterm birth (<34 weeks) and neonatal mortality compared with zidovudine-based ART (each given with lopinavir-ritonavir), but not compared with zidovudine alone . Given uncertainties regarding the trial results, potential interactions between TDF and lopinavir-ritonavir, and observational data suggesting safety of other TDF-containing regimens in pregnancy, we do not believe the evidence is clear enough to stop using TDF as a preferred agent (although we do not initiate TDF and lopinavir-ritonavir containing regimens during pregnancy). The British HIV Association also released a statement consistent with our position . (See "Safety and dosing of antiretroviral medications in pregnancy", section on 'Very preterm birth/neonatal mortality'.)
Enhanced prophylaxis against co-infections in advanced HIV infection (September 2017)
Co-infections are major causes of morbidity and mortality among HIV-infected individuals in resource-limited settings. In a randomized trial in sub-Saharan Africa of 1800 HIV-infected adults and children with a CD4 cell count <100 cells/microL initiating antiretroviral therapy (ART) with a CD4 cell count <100 cells/microL, enhanced prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX), isoniazid, fluconazole, azithromycin, and albendazole reduced all-cause mortality more than standard prophylaxis with TMP-SMX and guideline-based isoniazid administration . Despite the difference in pill burden, rates of self-reported ART adherence, virologic suppression, and serious drug-related adverse events were comparable across the two groups. Current World Health Organization recommendations for patients with advanced HIV infection include prophylaxis with TMP-SMX as well as screening and early treatment for cryptococcal and latent tuberculosis infection . (See "The impact of antiretroviral therapy on morbidity and mortality of HIV infection in resource-limited settings", section on 'Enhanced prophylaxis' and "The impact of antiretroviral therapy on morbidity and mortality of HIV infection in resource-limited settings", section on 'Prevention of coinfections'.)
Dolutegravir-containing ART as salvage for initial NNRTI failure (August 2017)
For HIV-infected patients who fail initial non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART), a protease inhibitor-based regimen is often used. New clinical trial data support the use of a dolutegravir-based regimen for certain patients. In a multicenter trial that included 624 patients failing initial NNRTI-based therapy, a dolutegravir-based regimen resulted in higher rates of virologic suppression (82 versus 69 percent) than a pharmacologically boosted lopinavir-based regimen (each was used with two nucleoside reverse transcriptase inhibitors [NRTIs], at least one of which was fully active) . For treatment of initial NNRTI failure, we use a dolutegravir-based regimen if genotype testing can confirm activity of at least one preferred NRTI. However, if genotype testing is not available or if there are no active NRTIs, we prefer a protease inhibitor-based regimen. (See "Selecting an antiretroviral regimen for treatment-experienced HIV-infected patients who are failing therapy", section on 'NNRTI-containing regimens'.)
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) . 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 . 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'.)
Letermovir for cytomegalovirus prophylaxis in allogeneic hematopoietic cell transplant recipients (November 2017)
Letermovir, a novel anti-cytomegalovirus (CMV) agent with intravenous and oral formulations, was approved by the US Food and Drug Administration and Health Canada in November 2017 for CMV prophylaxis in adult CMV-seropositive (CMV R+) allogeneic hematopoietic cell transplant (HCT) recipients [26-28]. Unlike ganciclovir and valganciclovir, letermovir is not myelosuppressive. In a phase III trial that has not yet been published, all-cause mortality among CMV-seropositive allogeneic HCT recipients was lower with letermovir than placebo . In addition, fewer patients receiving letermovir developed clinically significant CMV or were considered to have failed prophylaxis. (See "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Primary prophylaxis'.)
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 . 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'.)
Low effectiveness of the influenza vaccine in Australia (December 2017)
During the 2017 influenza season in the southern hemisphere, Australia reported very high numbers of influenza cases, multiple institutional outbreaks, and increased numbers of hospitalizations and deaths . Influenza A H3N2, which usually causes more severe disease than other strains, predominated. The overall adjusted vaccine effectiveness in Australia was estimated to be 33 percent, but only 10 percent for H3N2. Since the vaccine for the 2017-2018 influenza season in the northern hemisphere has the same composition as the vaccine used in the southern hemisphere during the 2017 season, there is concern that regions in the northern hemisphere could experience a severe influenza season, particularly if influenza A H3N2 virus circulates widely . (See "Seasonal influenza vaccination in adults", section on 'Low effectiveness in the Southern Hemisphere during the 2017 season'.)
Inactivated zoster vaccine in the United States (October 2017)
To date, only a live zoster vaccine has been available to prevent herpes zoster and postherpetic neuralgia; it is contraindicated in highly immunocompromised patients, and its efficacy is reduced in patients ≥70 years old. In October 2017, the US Food and Drug Administration approved an inactivated recombinant zoster vaccine that reduces the risk of herpes zoster by ≥90 percent, even among older individuals . The Advisory Committee on Immunization Practices has recommended the recombinant (administered in two doses) rather than the live attenuated vaccine for all adults ≥50 years old, although not all committee members agreed given the lack of data in minority groups and on the long-term vaccine safety and effectiveness in real-world settings . The optimal use of the inactivated vaccine continues to be assessed. Recommendations by the Centers for Disease Control and Prevention are forthcoming. (See "Vaccination for the prevention of shingles (herpes zoster)", section on 'Vaccine formulations'.)
pH1N1-containing influenza vaccine and miscarriage (October 2017)
Multiple studies have reported that administration of inactivated influenza vaccines to pregnant women is not associated with an increased risk of maternal, fetal, or neonatal complications. One exception is a case-control study of a possible increase in spontaneous abortion among the subgroup of women vaccinated with two consecutive pH1N1-containing vaccines during the 2010-2011 and 2011-2012 seasons . This study had several limitations that might have influenced the findings, and further confirmation is needed. We continue to strongly recommend routine influenza vaccination with trivalent or quadrivalent inactivated influenza vaccine, as the benefits outweigh any risks. (See "Influenza and pregnancy", section on 'Safety'.)
2017-2018 influenza immunization recommendations for the United States (September 2017)
The Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) have released recommendations for influenza immunization for the 2017-2018 season in the United States [36,37]. Routine influenza immunization with a licensed, age-appropriate vaccine (table 1) is recommended for all persons ≥6 months of age. Live attenuated influenza vaccine is not recommended for the 2017-2018 season. Pregnant women and persons with egg allergy of any severity can receive any licensed, age-appropriate inactivated influenza vaccine with standard immunization precautions. Although neither the ACIP nor the AAP provide a preference for a particular formulation, we favor a quadrivalent vaccine when available for adults <65 years and we recommend the high-dose vaccine for those ≥65 years. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Types of vaccine' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation' and "Influenza and pregnancy", section on 'Vaccination' and "Influenza vaccination in individuals with egg allergy", section on 'Safety of vaccines in patients with egg allergy'.)
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 . 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'.)
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 . 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".)
Xpert MTB/RIF Ultra for diagnosis of tuberculosis (December 2017)
The Xpert MTB/RIF Ultra (Xpert Ultra) was developed to improve the sensitivity of the Xpert MTB/RIF (Xpert), a molecular assay that detects Mycobacterium tuberculosis and rifampin resistance. It uses the same analyzer as Xpert but employs a new specimen cartridge and software. In a prospective study, the sensitivity of Xpert Ultra was higher than that of Xpert among 462 patients with culture-positive sputum (88 versus 83 percent) and among 137 patients with culture-positive but smear-negative sputum (63 versus 46 percent) . The World Health Organization (WHO) has recommended Xpert Ultra as a replacement for Xpert in all settings (where available) . The Xpert Ultra is available in the United States for research use only. (See "Diagnosis of pulmonary tuberculosis in HIV-uninfected adults".)
Self-administration of weekly isoniazid and rifapentine for latent tuberculosis infection (November 2017)
A 12-week regimen of weekly isoniazid (INH) and rifapentine (RPT) may be used for treatment of latent tuberculosis infection (LTBI) in certain high-risk patients and is typically administered via directly observed therapy (DOT). In a randomized trial including over 700 patients in the United States with LTBI, regimen completion rates with DOT, self-administration, or self-administration with reminders were 85, 78, and 77 percent, respectively . Administration of weekly INH and RPT via DOT remains preferable; self-administered INH and RPT is acceptable for patients who can reliably inform their providers promptly of any side effects and withhold the next dose pending provider review. (See "Treatment of latent tuberculosis infection in HIV-uninfected adults", section on 'Isoniazid and rifapentine'.)
Investigational assay for rapid diagnosis of drug-resistant tuberculosis (October 2017)
Molecular tests that detect drug resistance in Mycobacterium tuberculosis are useful for guiding initial therapeutic decisions until definitive culture-based drug-susceptibility testing results are available. An investigational molecular assay that rapidly detects resistance to fluoroquinolones (ofloxacin and moxifloxacin), aminoglycosides (kanamycin and amikacin), and isoniazid was evaluated in a study of more than 300 patients with positive sputum culture for M. tuberculosis . Compared with phenotypic drug susceptibility testing as the reference standard, sensitivity of the assay ranged from 71 to 88 percent for the different drugs, and specificity was ≥94 percent for all drugs except for moxifloxacin, for which specificity was 84 percent. It also performed well compared with DNA sequencing. This assay is a promising future tool for evaluation of patients with suspected drug-resistant tuberculosis. (See "Diagnosis of pulmonary tuberculosis in HIV-uninfected adults", section on 'Other assays'.)
Fexinidazole for human African trypanosomiasis (November 2017)
Available therapies for human African trypanosomiasis are toxic and difficult to administer. Fexinidazole is a promising new agent that can be administered orally without serious side effects. In a randomized trial including 394 patients with late-stage Trypanosoma brucei gambiense infection, the treatment success rate at 18 months was 91 percent with fexinidazole, compared with 98 percent with nifurtimox-eflornithine . There was no difference in the rate of treatment-related adverse events. The drug is in the process of being registered with regulatory authorities. (See "African trypanosomiasis: Clinical manifestations, diagnosis, and treatment", section on 'Drugs in the pipeline'.)
Point-of-care loiasis detection prior to mass ivermectin administration (November 2017)
Mass drug administration with ivermectin is used to eliminate onchocerciasis in highly endemic regions. However, ivermectin is avoided in patients coinfected with Loa loa because it can facilitate entry of L. loa microfilariae into the central nervous system, leading to serious adverse events. In a Cameroon field trial, a mobile phone-based video microscope (LoaScope) was used to evaluate for L. loa microfilaremia in over 16,000 individuals prior to mass ivermectin administration; approximately 2 percent were excluded from ivermectin distribution because of a L. loa microfilarial density above the risk threshold . More than 95 percent of those tested received ivermectin; no serious adverse events were observed. This test-and-not-treat strategy has the potential to facilitate onchocerciasis elimination in regions where L. loa is also endemic. (See "Onchocerciasis", section on 'Loa loa coinfection'.)
SEXUALLY TRANSMITTED DISEASES
Syphilis incidence in the United States (October 2017)
Syphilis causes a wide range of clinical syndromes and is associated with HIV transmission. The United States Centers for Disease Control and Prevention reported an approximately 18 percent increase in the rate of primary and secondary syphilis (the most infectious stages of the disease) in 2016, with 8.7 cases per 100,000 population, the highest rate since 1993 . More than 600 cases of congenital syphilis were also reported. Although syphilis rates increased among men and women, the rise was primarily attributable to men who have sex with men (MSM). These findings stress the importance of screening and treatment for sexually transmitted infection, especially in MSM and pregnant women. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients", section on 'Epidemiology'.)
VIRAL INFECTIONS, NON-HIV
Prevalence of oropharyngeal HPV infection in the United States (December 2017)
Although less prevalent than genital infection, oropharyngeal human papillomavirus (HPV) infection is common in the United States and disproportionately occurs in men. In a large cross-sectional study of men and women who provided an oral rinse sample for HPV DNA sampling, the prevalence among men was 12 percent for any HPV type and 7 percent for high-risk HPV types (in contrast to 3 and 1.4 percent among women) . Prevalence of high-risk HPV infection was especially high (22 percent) among men reporting two or more lifetime same-sex oral sex partners. These findings are consistent with the observed distribution of HPV-associated oropharyngeal cancer. (See "Human papillomavirus infections: Epidemiology and disease associations", section on 'Epidemiology of oropharyngeal infection'.)
Preliminary findings of Zika vaccine trials (October 2017, Modified December 2017)
Vaccine development for prevention of Zika virus infection is underway. Several inactivated vaccine candidates have been found to induce detectable neutralizing antibodies in phase 1 trials [48-50]. In one of the studies, serum from participants protected immunocompromised mice from developing disease after Zika virus challenge, indicating that vaccine-induced antibodies can prevent infection and disease in vivo . The efficacy of vaccination in preventing human infection with Zika virus will need to be evaluated in an endemic region with a larger study population. (See "Zika virus infection: An overview", section on 'Vaccine development'.)
New adjuvanted recombinant hepatitis B vaccine (November 2017)
Hepatitis B vaccination is the best way to prevent hepatitis B virus transmission. Available nonadjuvanted recombinant vaccines are effective and extremely safe, although they require three doses and 5 to 10 percent of patients do not respond. In November 2017, the US Food and Drug Administration granted conditional approval of a new adjuvanted vaccine (HEPLISAV-B) for adults 18 years and older . This vaccine, given in two doses, appears more immunogenic than the nonadjuvanted vaccines and is generally well tolerated. However, there are ongoing safety concerns regarding a potentially increased risk of acute myocardial infarction and immune mediated disorders, which will be further evaluated in a phase 4 study. The optimal use of this vaccine is thus still to be determined. (See "Hepatitis B virus vaccination", section on 'Single antigen vaccines'.)
Updated guidance for fetal ultrasound surveillance for congenital Zika virus syndrome (November 2017)
Prenatal ultrasound is used to screen for congenital Zika virus infection, although the sensitivity, specificity, and positive and negative predictive values are not well established, and optimal timing between exposure and initial and follow-up sonographic screening are unknown. A common protocol is to perform an initial ultrasound examination four weeks from the suspected exposure, followed by serial ultrasound examinations every four weeks, ensuring that at least one ultrasound is performed between 28 and 33 weeks of gestation. The Centers for Disease Control and Prevention has updated its guidance for women with laboratory evidence of infection and now states that clinicians may consider extending the time interval between follow-up ultrasound examinations in accordance with patient preferences and clinical judgment . In women with possible exposure during pregnancy but no laboratory evidence of infection, ultrasound screening beyond that obtained for routine prenatal care is no longer recommended. We agree with these recommendations. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Candidates'.)
Comparison of influenza diagnostic tests (October 2017)
Conventional reverse-transcriptase polymerase chain reaction (RT-PCR) is currently the preferred test for influenza due to its high sensitivity and specificity. Newer tests include rapid molecular assays using nucleic acid amplification and digital immunoassays (DIAs) using automated antigen detection. Both provide results more quickly than conventional RT-PCR and have higher sensitivity than traditional antigen detection tests. In a meta-analysis that compared various influenza assays with conventional RT-PCR for influenza A, the pooled sensitivities of rapid molecular assays and DIAs were 92 and 80 percent, respectively . Both had higher sensitivity than traditional rapid antigen tests (sensitivity 54 percent). If available, a rapid molecular assay can be used as an alternative to conventional RT-PCR. (See "Diagnosis of seasonal influenza in adults", section on 'Molecular assays' and "Diagnosis of seasonal influenza in adults", section on 'Choice of diagnostic test' and "Seasonal influenza in children: Clinical features and diagnosis", section on 'Approach to testing'.)
Increase in immune globulin dose for prevention of hepatitis A (September 2017)
Intramuscular immune globulin (IG) is protective against hepatitis A virus (HAV) infection and is used for pre- and postexposure prophylaxis instead of vaccination in certain situations. The level of neutralizing anti-HAV antibodies in GamaSTAN, the intramuscular IG product available in the United States, appears suboptimal, reflecting low prevalence of prior HAV infection among plasma donors . Therefore, increased dosing for GamaSTAN is now recommended when used for HAV prevention [55,56]. The new dose for preexposure prophylaxis is 0.1 mL/kg (for anticipated risk of exposure up to one month) or 0.2 mL/kg (for anticipated risk of exposure up to two months, with repeat dosing every two months for longer anticipated risk). The new dose for postexposure prophylaxis is 0.1 mL/kg. (See "Hepatitis A virus infection: Prevention", section on 'Passive immunization'.)
Third dose of MMR for prevention of mumps in an outbreak setting (September 2017)
In the setting of a mumps outbreak, in addition to ensuring that incompletely immunized individuals receive the standard two-dose measles, mumps, and rubella (MMR) vaccine series, public health authorities may recommend a third dose of the MMR vaccine under certain circumstances (eg, two-dose vaccination coverage >90 percent, intense exposure setting, high attack rate). During a mumps outbreak at a university with over 20,000 enrolled students, almost all of whom had previously received two vaccine doses, nearly 5000 students received a third MMR dose . The mumps attack rate (259 cases overall) was lower among students who had received three rather than two vaccine doses (6.7 versus 14.5 cases per 1000 persons); in an adjusted analysis, the third MMR dose was associated with a 78 percent lower risk of mumps. (See "Mumps", section on 'Prevention'.)
Severity of maternal Zika virus infection and birth outcome (September 2017)
Maternal-to-fetal transmission of Zika virus can occur with either symptomatic or asymptomatic maternal infection; the risk factors for transmission are unknown. In a prospective study from Rio de Janeiro of women with confirmed Zika virus infection during pregnancy, no association was observed between maternal disease severity (signs, symptoms, virus load) or prior dengue virus infection and adverse birth outcome defined as fetal loss or birth of a live infant with grossly abnormal clinical or brain imaging findings . This finding supports the Centers for Disease Control and Prevention (CDC) recommendation for serial fetal ultrasound examinations in pregnant women with laboratory evidence of Zika virus infection, regardless of maternal disease severity. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Risk of vertical transmission and anomalies'.)
Lack of benefit of cytomegalovirus prophylaxis in critically ill patients (August 2017)
Cytomegalovirus (CMV) reactivation is common in critically ill immunocompetent patients and is associated with increased length of hospital and intensive care unit (ICU) stay, sepsis, and mortality. However, there is no evidence that antiviral prophylaxis in these patients leads to improved outcomes. In a placebo-controlled trial of CMV-seropositive immunocompetent patients with critical illness due to sepsis or trauma, prophylaxis with intravenous ganciclovir was associated with a reduced incidence of CMV reactivation. However, there was no difference between the groups in levels of the pro-inflammatory cytokine, interleukin-6 (the primary outcome), or in incidence of secondary bacteremia or fungemia, ICU length of stay, or mortality . (See "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults", section on 'Prophylaxis against reactivation'.)
HEV infection in Europe and outbreaks in Africa (August 2017)
Hepatitis E virus (HEV) infection has a global distribution and is most commonly transmitted through contaminated food or water. In July 2017, World Health Organization reported an outbreak of HEV in Nigeria, where a humanitarian crisis has resulted in poor access to safe water and health services . An earlier outbreak in nearby Niger had been reported in May 2017. In a separate 2017 surveillance analysis, the European Centre for Disease Prevention reported an increase in the number of confirmed HEV cases in Europe from 514 cases in 2005 to 5617 cases in 2015 . It is unclear if this represents a true rise in HEV incidence in Europe or an increase in case detection due to growing awareness and testing for HEV. (See "Hepatitis E virus infection", section on 'Epidemiology'.)
Novel HBV mutation associated with tenofovir and entecavir failure (August 2017)
For patients with chronic hepatitis B virus (HBV) infection, tenofovir is one of the preferred antiviral agents. To date, no signature tenofovir-resistance mutations have been identified in HBV. However, in a report of two HBV-infected patients with persistent viremia despite therapy with tenofovir and entecavir, molecular analyses identified a shared distinct mutation, rtS78T/sC69, which was associated with decreased susceptibility to both tenofovir and entecavir in vitro . The prevalence and significance of this mutation remains to be determined. (See "Tenofovir and adefovir for the treatment of chronic HBV infection", section on 'Risk of resistance'.)
Glecaprevir-pibrentasvir and sofosbuvir-velpatasvir-voxilaprevir for chronic HCV infection (August 2017)
Treatment options for patients with chronic hepatitis C virus (HCV) continue to grow. Two new combination therapies, glecaprevir-pibrentasvir and sofosbuvir-velpatasvir-voxilaprevir, were recently approved by the Food and Drug Administration in the United States and are expected to be approved in Europe this year. Glecaprevir-pibrentasvir is highly effective for patients with genotypes 1 through 6 infection, offers the possibility of an eight-week regimen for most patients without cirrhosis, and can be used in patients with renal impairment (including those on dialysis) [63-66]. It is now one of our preferred regimens for all genotypes; regimen duration depends on the genotype, the presence of cirrhosis, and the treatment history (algorithm 1 and algorithm 2 and algorithm 3 and algorithm 4). Sofosbuvir-velpatasvir-voxilaprevir is highly effective in patients with genotypes 1 through 6 infection who have failed a prior direct acting antiviral (DAA) regimen and is now the main treatment option for those who have failed an NS5A inhibitor-containing regimen . Like other contemporary DAA regimens, these new combinations are well tolerated, with common but mild side effects. (See "Treatment regimens for chronic hepatitis C virus genotype 1 infection in adults", section on 'Selection of treatment regimens' and "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults", section on 'Selection of treatment regimen' and "Treatment regimens for chronic hepatitis C virus genotypes 4, 5, and 6 infection in adults", section on 'Selection of treatment regimens'.)
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 5) . 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 . 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 .
●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 . 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'.)
OTHER INFECTIOUS DISEASES
IDSA guidelines on acute diarrhea (November 2017)
The Infectious Diseases Society of America updated its guidelines on the diagnosis and management of infectious diarrhea . They recommend confirmatory stool culture and susceptibility testing when culture-independent diagnostic tests are positive for clinically important bacterial pathogens. They highlight the need for careful interpretation of multiplex molecular panels, which simultaneously test for multiple organisms by detecting genetic material, do not always indicate infection with a viable organism, and frequently identify more than one potential pathogen. The guidelines also emphasize reserving empiric antibiotic therapy for select patients, including those with severe illness or immunocompromising conditions. Our approach is generally consistent with these guidelines. (See "Approach to the adult with acute diarrhea in resource-rich settings".)
Lack of benefit with corticosteroid use for acute bronchitis (September 2017)
Corticosteroids are frequently used for symptom relief in patients with acute bronchitis, although no data support use for this indication. In a randomized trial comparing oral prednisolone with placebo in 401 adult outpatients with acute cough, symptomatic lower respiratory tract infection, and no indication for antibiotic treatment, there was no difference in symptom severity, duration of cough, or peak flow . Patients with chronic lung disease or asthma were excluded. This study supports our advice to not prescribe corticosteroids in patients with acute bronchitis, apart from those with concurrent asthma or chronic obstructive pulmonary disease (COPD) exacerbations. (See "Acute bronchitis in adults", section on 'For cough'.)
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