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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.
Restriction of fluoroquinolone use in uncomplicated infections (May 2016)
The US Food and Drug Administration (FDA) has stated that the serious adverse effects associated with fluoroquinolones generally outweigh the benefits for patients with uncomplicated acute sinusitis, acute bronchitis, and urinary tract infections who have other treatment options . For patients with these infections, fluoroquinolones should be reserved for those who have no alternative treatment options. This announcement was based on an FDA safety review showing that systemic fluoroquinolone use is associated with disabling and potentially permanent serious side effects, including those involving the tendons, muscles, joints, nerves, and central nervous system. (See "Fluoroquinolones", section on 'Restriction of use for uncomplicated infections'.)
Oral fluoroquinolone use and serious arrhythmia (March 2016)
QT interval prolongation and torsades de pointes have been associated with fluoroquinolone use, but the degree to which fluoroquinolones block cardiac potassium channels and thereby cause QT prolongation varies by agent. The risk of serious arrhythmia during fluoroquinolone therapy was evaluated in a cohort of adults aged 40 to 79 years of age in Denmark and Sweden; arrhythmic events were compared for 909,656 courses of fluoroquinolones (ciprofloxacin in 83 percent, norfloxacin in 12 percent, ofloxacin in 3 percent, moxifloxacin in 1 percent, other in 1 percent) and 909,656 courses of penicillin, an antibiotic not associated with arrhythmia . There was no increase in the risk of serious arrhythmia with fluoroquinolones compared with penicillin. This finding conflicts with results from earlier studies, and may be explained in part by the predominant use of ciprofloxacin in this cohort, with its smaller impact on QT prolongation. (See "Fluoroquinolones", section on 'QT interval prolongation and arrhythmia'.)
Oritavancin interference with coagulation tests (February 2016)
Oritavancin is a glycopeptide antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA). Although oritavancin has no effect on the coagulation system in vivo, it falsely prolongs the activated partial thromboplastin time (aPTT), prothrombin time/international normalized ratio (PT/INR), and activated clotting time (ACT) by binding to phospholipid reagents used in laboratory testing. In 2016, the US Food and Drug Administration (FDA) labeling was revised to include new time frames for concern as to interference with coagulation tests of up to five days for aPTT, 12 hours for PT/INR, and 24 hours for ACT, following a single intravenous (IV) dose of oritavancin . Coagulation test interference can make the monitoring of unfractionated heparin (UFH) and warfarin unreliable within these time frames. For patients who require aPTT monitoring within five days of oritavancin, anti-factor Xa activity testing may be used. Patients who require a heparin anticoagulant and do not have access to anti-factor Xa testing could be treated with low molecular weight (LMW) heparin instead of UFH. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Prolonged baseline aPTT' and "Pharmacology of antimicrobial agents for treatment of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus", section on 'Drug interactions' and "Oritavancin: Drug information".)
Outbreak of Burkholderia cepacia infection associated with contaminated oral liquid docusate (June 2016)
In June 2016, a multistate outbreak of Burkholderia cepacia infection was reported in the United States . B. cepacia typically causes lung colonization and infection in patients with cystic fibrosis (CF), but most cases in this outbreak have involved mechanically ventilated intensive care unit patients without CF. The types of infections involved have not yet been reported. Because cases in one state have been associated with contaminated oral liquid docusate, the United States Centers for Disease Control and Prevention (CDC) recommends that facilities not use liquid docusate products for any patient. PharmaTech LLC, the manufacturer of the contaminated product, Diocto Liquid, has voluntarily recalled all non-expired lots . Updated information about the outbreak and public health reporting can be found on the CDC’s website. (See "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults", section on 'Outbreak of Burkholderia cepacia infection'.)
Etiology of community-acquired pneumonia (April 2016)
Multiple studies of patients with community-acquired pneumonia (CAP) have identified an etiologic agent in fewer than half of cases. In a study of hospitalized adults with CAP in the United Kingdom that used both bacterial cultures and comprehensive multiplex molecular testing for bacteria and viruses of lower respiratory tract specimens, a pathogen was identified in 87 percent of cases by molecular methods . Culture-based methods detected a pathogen in only 39 percent of cases. Haemophilus influenzae and Streptococcus pneumoniae were the most common agents detected, followed by a wide variety of pathogens. Viruses were present in 30 percent of cases; 82 percent of these were detected in specimens that also tested positive for bacteria. A caveat is that contamination of specimens with upper respiratory tract secretions could cause false positive results . (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Inpatients'.)
Indications for antibiotics in the management of skin abscess (March 2016)
The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has raised uncertainty regarding the role of antimicrobial therapy for treatment of skin abscess following incision and drainage. In a randomized trial including 1220 patients >12 years of age (median 35 years) with drained skin abscess (≥2 cm in diameter) comparing trimethoprim sulfamethoxazole (TMP-SMX, 320 mg/1600 mg twice daily) with placebo, the cure rate 7 to 14 days after treatment was higher in the TMP-SMX group (80.5 versus 73.6 percent); wound cultures were positive for MRSA in 45 percent of cases . Based on these findings, abscess size ≥2 cm in diameter is a useful threshold for guiding decisions regarding use of antibiotic therapy for adjunctive treatment of skin abscess.
Additional factors for which we recommend antibiotic therapy include the presence of multiple lesions, extensive surrounding cellulitis, associated comorbidities or immunosuppression, signs of systemic infection, or inadequate clinical response to incision and drainage alone; we suggest antibiotic therapy for patients with an indwelling device or high risk for transmission of S. aureus to others. For otherwise healthy patients with none of these factors, we suggest not administering antimicrobial therapy. (See "Skin abscesses, furuncles, and carbuncles", section on 'Role of antibiotics'.)
Isavuconazole for mucormycosis (August 2016)
Isavuconazole is a broad-spectrum triazole that has in vitro activity against the agents of mucormycosis. It is an option for step-down or salvage therapy for patients with mucormycosis after initial treatment with amphotericin B, although clinical evidence supporting its use is limited. Isavuconazole was evaluated in a multicenter open-label single-arm study (the VITAL study) that included 37 patients with proven or probable mucormycosis . All-cause mortality through day 42 was 38 percent, and overall complete or partial response rate at the end of treatment was 32 percent for primary treatment and 36 percent for treatment of mucormycosis refractory to other antifungals. In a matched case-control analysis that compared patients who received isavuconazole for primary therapy of mucormycosis with contemporary controls who received amphotericin B (mostly a lipid formulation), crude and weighted all-cause mortality were similar in those who received isavuconazole versus amphotericin B followed by posaconazole. These data suggest that isavuconazole has some clinical efficacy in treating mucormycosis, but it is not possible to draw firm conclusions given the nonrandomized study design and the small study size. Amphotericin B remains the treatment of choice for initial therapy. (See "Mucormycosis (zygomycosis)", section on 'Step-down therapy'.)
IDSA guidelines on the management of aspergillosis (July 2016)
The Infectious Diseases Society of America released updated guidelines for the treatment of aspergillosis [10,11]. Voriconazole remains the mainstay of therapy for invasive aspergillosis. In contrast with the previous version of the guidelines, the updated version suggests consideration of combination therapy with voriconazole plus an echinocandin for initial therapy of severe invasive aspergillosis, particularly in patients with hematologic malignancy and/or in those with profound and persistent neutropenia. We generally agree with these guidelines and suggest combination therapy with voriconazole plus an echinocandin for patients with severe, microbiologically documented invasive aspergillosis, but we also consider combination therapy for all patients with an immunocompromising condition that led to disease. (See "Treatment and prevention of invasive aspergillosis", section on 'Guidelines'.)
Emergence of Candida auris, a multidrug-resistant Candida species (July 2016)
In 2016, the United States Centers for Disease Control and Prevention (CDC) and Public Health England issued warnings about the emergence of a multidrug-resistant Candida species, C. auris [12,13]. This pathogen has caused invasive health care-associated infections and outbreaks outside the United States and is associated with high mortality rates . It has been detected in nine countries on four continents, including Japan, South Korea, India, South Africa, Kuwait, Pakistan, the United Kingdom, Colombia, and Venezuela. Only one isolate has been detected in the United States as part of surveillance. C. auris requires specialized methods for identification and it could therefore be misidentified as another yeast when using traditional biochemical methods. Nearly all C. auris isolates have had high minimum inhibitory concentrations (MICs) for fluconazole, suggesting that they are fluconazole-resistant. More than half of isolates have had high MICs for voriconazole, and a lower proportion for amphotericin B and echinocandins. Some isolates have had elevated MICs for all three major antifungal classes (azoles, polyenes, echinocandins).
Reducing transmission of malaria by blood transfusion using a pathogen inactivation technology (May 2016)
Pathogen inactivation technologies are treatments that can be applied to blood products before they are transfused, to reduce transmission of viable infectious agents. In Ghana, where malaria is endemic and testing of donated blood for parasitemia is not routinely available, a randomized trial demonstrated that treatment of whole blood with one of these methods (riboflavin [vitamin B2] plus ultraviolet [UV] light) was able to significantly reduce transfusion-transmitted malaria . (See "Pathogen inactivation of blood products", section on 'Potential benefits'.)
Condom use in HIV serodiscordant couples (August 2016)
HIV serodiscordant couples may question whether continued condom use is necessary for HIV prevention if the HIV-infected partner is on antiretroviral therapy (ART). One observational study followed over 900 serodiscordant couples (both heterosexual couples and men who have sex with men [MSM]) in whom the HIV-infected partner was virally suppressed on ART and who chose not to use condoms . After more than 1200 couple-years of follow-up, there were no intra-couple transmission events. Ten MSM and one heterosexual partner acquired HIV infection during the study period, but viral sequence analysis suggested that these infections were not transmitted from the long-term HIV-infected partner. We continue to encourage condom use in HIV serodiscordant couples, as condoms offer protection from other sexually transmitted infections and provide back-up for potential periods of loss of virologic suppression. We advise couples who choose not to use condoms that the risk of HIV transmission in the setting of stable virologic suppression of the infected partner, while apparently negligible, cannot be ruled out completely. (See "HIV infection: Risk factors and prevention strategies", section on 'Serodiscordant couples'.)
HIV treatment to prevent transmission (August 2016)
Growing evidence has bolstered the concept that successful antiretroviral therapy (ART) of HIV-infected individuals substantially reduces the risk of sexual HIV transmission. Final analysis of a multinational randomized trial (HPTN 052) of over 1700 HIV serodiscordant heterosexual couples demonstrated that early ART for the HIV-infected partner, compared with delaying ART until certain clinical parameters were met, reduced HIV transmission risk by 93 percent . All participants received condoms and risk reduction counseling. There were no linked transmissions (determined by detecting the same virus in both partners through viral sequencing) from HIV-infected individuals who had achieved stable viral suppression on ART; all eight linked transmissions from HIV-infected individuals using ART occurred within three months of ART initiation or in the setting of ART failure. This preventive benefit of ART is one of the reasons that early ART is recommended for all HIV-infected individuals, regardless of CD4 cell count. (See "HIV infection: Risk factors and prevention strategies", section on 'Treatment as prevention' and "When to initiate antiretroviral therapy in HIV-infected patients", section on 'Benefits of antiretroviral therapy'.)
WHO recommendations for infant prophylaxis to prevent mother-to-child HIV transmission (July 2016)
The World Health Organization (WHO) has updated its guidelines on the use of antiretroviral agents to manage and prevent HIV infection . One major change from previous WHO statements involves post-exposure prophylaxis of infants born to HIV-infected mothers. The recommended regimen for infant prophylaxis now takes into account the infant's risk of infection, as determined by the timing of maternal infection and maternal antiretroviral treatment, in addition to the type of infant feeding; a two-drug regimen is recommended for high-risk infants. This recommendation was based, in part, on earlier data that demonstrated a lower HIV transmission rate with dual-agent rather than single-agent prophylaxis among infants born to mothers who had not received antiretroviral agents during pregnancy. (See "Prevention of mother-to-child HIV transmission in resource-limited settings", section on 'Infant antiretroviral use'.)
Viral dynamics and symptom onset in acute HIV infection (May 2016)
A recent study that closely followed 50 acutely HIV-infected patients who had been identified by prospective viral testing of high-risk individuals provides precise information on the clinical features and viral dynamics shortly following infection . Although almost all subjects had at least one reported symptom or sign during the first four weeks of infection, these were mainly short-lived, nonspecific, and unlikely to have brought the individual to clinical attention outside of a study setting. The highest frequency of symptoms and signs were observed just before peak viremia occurred, approximately two weeks after the initial detection of viral RNA. These results highlight the difficulty of suspecting acute HIV infection by clinical features alone and thus, the importance of repeated HIV screening in high-risk individuals. (See "Acute and early HIV infection: Clinical manifestations and diagnosis", section on 'Clinical features'.)
Nonoccupational postexposure prophylaxis to prevent HIV infection (April 2016)
A discrete course of antiretroviral therapy (ART) administered after a possible exposure to HIV may reduce the risk of HIV acquisition. The US Centers for Disease Control and Prevention (CDC) has issued updated guidelines on HIV prophylaxis following a nonoccupational exposure . A 28-day course of a three-drug regimen (eg, tenofovir disoproxil fumarate-emtricitabine plus either raltegravir or dolutegravir) should be offered to patients who present within 72 hours of a high-risk exposure (eg, condomless receptive or insertive vaginal or anal intercourse or a percutaneous exposure to blood or bloody body fluids) from a source who is HIV-infected or is at high risk for HIV infection. Exposed patients should be educated about the signs and symptoms of acute HIV infection, and have follow up HIV testing. (See "Nonoccupational exposure to HIV in adults".)
Pre-exposure prophylaxis against HIV using a dapivirine-containing vaginal ring (March 2016)
For high-risk HIV-uninfected individuals, pre-exposure prophylaxis (PrEP) using antiretroviral medications can prevent new HIV infections. Among heterosexual women, clinical trials of PrEP with both oral and topical tenofovir-containing formulations have yielded variable results, thus raising interest in other PrEP modalities in this population. A randomized trial of 2692 women in Africa evaluated the efficacy of a monthly vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine . Compared with a placebo vaginal ring, dapivirine reduced the incidence of HIV infection by 27 percent, and there was no difference in adverse events between the two groups. Dapivirine efficacy was higher among those with increased adherence. The dapivirine ring is not yet clinically available but is being evaluated in an open-label study to assess real world effectiveness. (See "Pre-exposure prophylaxis against HIV infection", section on 'Heterosexual women'.)
Pregnancy risk with progestin-releasing implants in HIV-infected women using efavirenz (March 2016)
Potential drug interactions are important considerations when choosing hormonal contraception for HIV-infected women on antiretroviral therapy (ART). Two recent observational studies from Africa have suggested that drug interactions between the non-nucleoside reverse transcriptase inhibitor efavirenz and progestin-releasing implants (both levonorgestrel and etonogestrel) are associated with decreased contraceptive efficacy [21,22]. In one of these studies, the adjusted pregnancy incidence among over 6000 women using progestin-releasing implants was three times higher in those using an efavirenz- versus a nevirapine-based regimen . If a progestin-releasing implant is the preferred contraceptive method for a women taking an efavirenz-based ART regimen, a second form of contraception should also be used. (See "HIV and women", section on 'Drug interactions'.)
No benefit of routine glucocorticoids for cryptococcal meningitis in HIV-infected patients (February 2016)
The preferred treatment approach for HIV-infected patients with cryptococcal meningoencephalitis includes combination antifungal therapy for the induction phase of therapy followed by consolidation therapy with fluconazole alone. There is no role for empiric glucocorticoids during induction therapy. This is in contrast to other conditions (eg, tuberculous meningitis) in which they are routinely administered as part of initial therapy. The use of glucocorticoids for patients with cryptococcal meningitis was evaluated in a randomized trial that included 451 HIV-infected patients from Asia and Africa . Patients received amphotericin plus fluconazole with or without dexamethasone. The trial was stopped early after an interim analysis found no difference in mortality or the rate of immune reconstitution inflammatory syndromes (IRIS) between the two groups at 10 weeks. In addition, patients who received adjunctive corticosteroids were less likely to have a good neurologic outcome, had slower rates of fungal clearance, and were more likely to develop an adverse event (eg, infection, renal or cardiac event). Although glucocorticoids are not routinely recommended for induction therapy, they may have a role in the management of patients who develop IRIS following initiation of antifungal therapy. (See "Treatment of Cryptococcus neoformans meningoencephalitis in HIV-infected patients", section on 'Induction and consolidation'.)
Virus-specific T cell infusions for patients with primary immunodeficiencies and hematopoietic cell transplant (June 2016)
Viral infections, particularly with cytomegalovirus, Epstein-Barr virus, and adenovirus, are a leading cause of death in patients with severe combined immunodeficiency (SCID) and other forms of moderate-to-severe primary immunodeficiency (PID), both before and after hematopoietic cell transplantation (HCT). Investigational infusions of virus-specific T cells (VST) from either stem cell donors or third-party donors have been evaluated to treat and/or prevent these life-threatening viral infections. One retrospective series examined 26 patients with a PID requiring HCT who had at least one documented serious viral infection and were treated with VST either before or after HCT . Complete or partial antiviral response was seen in 76 to 100 percent of patients, depending upon the particular virus. An additional 10 patients were treated preventively with VST prior to HCT. Of these, eight remained free of the most common serious viral infections. This therapy is still experimental, but commercial entities are developing these cellular products and they may be available for more widespread use in a few years. (See "Severe combined immunodeficiency (SCID): An overview", section on 'Treatment'.)
Risk of Pneumocystis pneumonia and cytomegalovirus infections with idelalisib (March 2016)
Idelalisib is a phosphatidylinositol 3-kinase inhibitor used for the treatment of chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Seven clinical trials of idelalisib used in combination with other agents have been halted due to an increase in serious adverse events and fatalities in patients receiving idelalisib . The majority of adverse events were infections, including sepsis and pneumonia. In particular, an increased number of cases of Pneumocystis pneumonia and cytomegalovirus (CMV) infection was observed in the idelalisib groups of three trials . The manufacturer has suggested that patients taking idelalisib receive Pneumocystis prophylaxis. They have also suggested that patients taking idelalisib be monitored for CMV reactivation and that idelalisib be discontinued in patients with evidence of infection or viremia. Changes to the prescribing information are expected, pending review by the US Food and Drug Administration. (See "Risk of infections in patients with chronic lymphocytic leukemia", section on 'Idelalisib' and "Prevention of infections in patients with chronic lymphocytic leukemia", section on 'Ibrutinib and idelalisib'.)
Inactivated influenza vaccine for 2016-2017 season in the northern hemisphere (August 2016)
The effectiveness of seasonal influenza vaccines varies from season to season and is determined by a number of factors, including the match between circulating influenza strains and influenza strains in the vaccine. During the 2015-2016 influenza season, data from the United States Influenza Vaccine Effectiveness Network indicated that inactivated influenza vaccine (IIV) was 63 percent effective in preventing influenza in children, but live attenuated influenza vaccine (LAIV) was not effective . Findings of poor or lower than expected LAIV effectiveness were also noted during the 2013-2014 and 2014-2015 seasons in the United States. These findings are inconsistent with studies sponsored by the manufacturer and studies from other countries that found LAIV was effective (ranging from 46 to 58 percent) during the 2015-2016 season [28-31]; however, LAIV was less effective than IIV in all of these studies . In June 2016, the United States Advisory Committee on Immunization Practices (ACIP) voted to recommend that LAIV not be used during the 2016-2017 influenza season; this recommendation must be approved by the United States Centers for Disease Control and Prevention (CDC) director before it becomes CDC policy . While some countries have elected to continue using LAIV , we suggest IIV rather than LAIV for the 2016-2017 influenza season in the northern hemisphere. (See "Seasonal influenza in children: Prevention with vaccines", section on 'IIV versus LAIV' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation'.)
Oral vaccine to prevent cholera in high-risk travelers (June 2016)
Cholera, caused by infection with the bacterium Vibrio cholerae, is characterized by severe watery diarrhea, which can rapidly lead to dehydration. In June 2016, a live attenuated oral cholera vaccine (Vaxchora) was approved by the US Food and Drug Administration for prevention of cholera caused by serogroup O1 in adults 18 through 64 years of age traveling to affected areas . Most travelers are at low risk for cholera infection; those who warrant vaccination include aid, refugee, and health care workers planning to work among or near displaced populations (eg, in crowded camps and urban slums) in endemic or epidemic settings. Long-stay travelers in very high-risk countries are also appropriate vaccine recipients. In a trial of healthy volunteers, a single dose of vaccine given prior to an oral challenge with a V. cholerae O1 strain was 80 to 90 percent effective in preventing moderate to severe cholera . The effectiveness of Vaxchora for populations living in cholera-affected areas has not been established. (See "Immunizations for travel", section on 'Cholera vaccine'.)
Nonmedical vaccine exemptions and risk of measles and pertussis (March 2016)
Despite universal childhood vaccination programs in the United States, the incidence of measles and pertussis has increased since the early 2000s. A systematic review evaluated the association between vaccine refusal and measles or pertussis infection in the United States between 2000 and 2015 . Nearly 60 percent of 1416 measles cases occurred in people who were not vaccinated against measles. Among the 574 unvaccinated cases who were old enough to have received measles vaccine, 71 percent refused it for nonmedical reasons (eg, religious or philosophic beliefs). Nonmedical exemptions also were prevalent among unvaccinated cases of pertussis (ranging from 59 to 93 percent in eight outbreaks). These findings confirm that nonmedical exemptions increase the risk of vaccine-preventable illness in the unvaccinated individual and, by reducing overall community immunity, increase the risk of illness in children too young to be vaccinated, people with medical contraindications to vaccination, and vaccinated people with waning immunity . (See "Standard childhood vaccines: Parental hesitancy or refusal", section on 'For the individual'.)
Duration of protection after hepatitis B vaccination (February 2016)
After completion of the hepatitis B vaccination series, levels of protective antibody decline over time. Protection against clinical disease is provided by memory cells, which elicit an anamnestic antibody response. However, the duration of protection is unknown. In a long-term follow-up study, 51 percent of 243 Alaska Native adults and children maintained protective antibody levels 30 years after completion of the hepatitis B vaccine series and 88 percent of those without protective levels mounted an anamnestic response . These findings suggest that protection persists for up to 30 years and support the current hepatitis B immunization schedule, which does not include a booster dose for patients with normal immune status. (See "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Duration of immunity' and "Hepatitis B virus vaccination", section on 'Duration of protection'.)
Option for shortened MDR-TB regimen in updated WHO guidelines (May 2016)
The conventional treatment regimen for multidrug-resistant tuberculosis (MDR-TB) consists of a fluoroquinolone, an injectable agent, and at least two other core second-line agents for a total duration of 20 to 26 months. Updated World Health Organization (WHO) guidelines present the option of a shortened regimen for nonpregnant patients with MDR-TB who have no extrapulmonary disease, an isolate known to be susceptible to fluoroquinolones and injectable antituberculous agents, and no prior exposure to second-line agents for more than one month . The shortened regimen consists of an intensive phase (four to six months of high-dose isoniazid, ethambutol, pyrazinamide, gatifloxacin [or moxifloxacin], kanamycin, prothionamide, and clofazimine) followed by a continuation phase (five months of ethambutol, pyrazinamide, gatifloxacin [or moxifloxacin], and clofazimine). Support for this regimen comes in part from a large study from Bangladesh that reported high rates of favorable bacteriologic outcomes with a similar 9 to 12-month regimen . The new WHO guidance also indicates that patients with rifampin monoresistance should be treated as for MDR-TB. Patients with known or suspected MDR-TB who do not meet criteria for the shortened MDR-TB regimen should be treated with the conventional regimen. (See "Diagnosis, treatment, and prevention of drug-resistant tuberculosis", section on 'General principles'.)
Urine mycobacterial antigen lipoarabinomannan (LAM) for TB testing (March 2016)
Urine-based detection of mycobacterial antigen lipoarabinomannan (LAM) is a bedside assay to diagnose hematogenously disseminated tuberculosis (TB). LAM plus routine diagnostic testing (smear microscopy, Xpert-MTB/RIF and culture) was compared with routine diagnostic testing alone in a randomized trial involving over 2500 HIV-infected hospitalized adults in four African countries with at least one symptom suggesting TB . All-cause mortality at eight weeks was decreased in the group that had LAM testing to guide initiation of antituberculosis treatment (relative risk reduction 17 percent). Neither patients nor health care workers were masked to group allocation or test results, presenting a risk of bias. Nonetheless, we are in agreement with the World Health Organization (WHO), which favors use of urine LAM testing for hospitalized HIV-infected patients with signs and symptoms of tuberculosis and CD4 ≤100 cells/microL, and HIV-infected patients who are seriously ill regardless of CD4 count. (See "Epidemiology, clinical manifestations, and diagnosis of tuberculosis in HIV-infected patients", section on 'Urine antigen detection'.)
Nontuberculous mycobacteria in patients with cystic fibrosis (February 2016)
Nontuberculous mycobacteria (NTM) are in the sputum of up to 20 percent of patients with cystic fibrosis (CF), and some of these patients develop progressive NTM pulmonary disease (NTM-PD). New guidelines provide recommendations for the screening, diagnosis, and management of NTM in CF patients . Annual screening of sputum is recommended for all expectorating patients. Patients with persistently positive results or symptoms suggesting NTM-PD should have a full evaluation including high-resolution computed tomography (HRCT) and sometimes bronchoscopy to determine if they meet criteria for NTM pulmonary disease. For any patient on chronic azithromycin therapy suspected of NTM infection, azithromycin should be stopped temporarily pending further diagnostic evaluation, to reduce the risk of inducing resistance because of monotherapy. (See "Cystic fibrosis: Antibiotic therapy for lung disease", section on 'Nontuberculous mycobacteria'.)
Artemisinin combination therapy for uncomplicated falciparum malaria in pregnancy (March 2016)
An artemisinin combination therapy (ACT) is the regimen of choice for treatment of pregnant women with uncomplicated chloroquine-resistant P. falciparum malaria during the second or third trimesters. This approach is supported by a recent large trial including 3428 pregnant women in four African countries (Burkina Faso, Ghana, Malawi and Zambia) randomly assigned to treatment with one of four ACT regimens (artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine) with cure rates of 95 to 99 percent . Dihydroartemisinin-piperaquine had the best efficacy and an acceptable safety profile, with the benefit of a longer post-treatment prophylactic effect. Artemether-lumefantrine was associated with the fewest adverse effects and acceptable cure rates, but had the shortest post-treatment prophylactic effect; this may be particularly important in high-transmission settings where a prolonged post-treatment prophylactic effect can reduce morbidity by decreasing the frequency of new infections. (See "Prevention and treatment of malaria in pregnant women", section on 'Second and third trimesters'.)
Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy (March 2016, Modified March 2016)
For pregnant women who live in areas with medium and high malaria transmission, we agree with the World Health Organization (WHO) strategy to provide intermittent preventive treatment during pregnancy (IPTp). Sulfadoxine-pyrimethamine (SP) has been an effective drug for IPT, although its benefit may be limited given the emergence of drug resistance. Two trials in Kenya and Uganda (where SP resistance is widespread) have evaluated the efficacy of dihydroartemisinin-piperaquine (DP) for IPTp:
●In a trial including over 1500 Kenyan women randomly assigned to receive IPT with SP or DP, IPT with DP resulted in a lower prevalence of malaria infection at delivery (3 versus 10 percent) and fewer episodes of clinical malaria during pregnancy (38 versus 6 episodes) compared with IPT with SP . The trial was not powered to detect small differences in neonatal outcomes.
●In a trial including 300 pregnant adolescents and women in Uganda randomly assigned to receive IPT with SP (three doses), DP (three doses), or DP (monthly treatments starting as early as 16 weeks of gestation) , the prevalence of histopathologically confirmed placental malaria was lower among those who received monthly DP (27 percent) than among those who received three doses of DP (34 percent) or IPT with SP (50 percent). In addition, monthly DP treatment was superior to three-dose DP with regard to several outcomes, including adverse birth outcomes and the incidence of symptomatic malaria.
DP is a promising alternative agent for IPTp; further study of DP dosing in pregnancy is needed. (See "Prevention and treatment of malaria in pregnant women", section on 'Intermittent preventive treatment during pregnancy'.)
SEXUALLY TRANSMITTED DISEASES
Treatment failure of pharyngeal gonorrhea following combination antimicrobial therapy (July 2016)
Because of concerns about the decreasing susceptibility of Neisseria gonorrhoeae to several classes of antibiotics, combination antimicrobial therapy with ceftriaxone plus a second agent, preferably azithromycin, is the recommended treatment for uncomplicated gonorrhea. However, treatment failure following combination therapy has now been reported, in a heterosexual man from the United Kingdom who presented with both urogenital and pharyngeal infection . Although the urogenital infection was successfully treated with ceftriaxone plus azithromycin, the pharyngeal infection persisted, and decreased susceptibility to both agents was detected in the post-treatment isolate. This report, in addition to surveillance reports suggesting increasing rates of decreased susceptibility to azithromycin in N. gonorrhoeae isolates in the United States , highlights the need for novel treatment strategies for gonorrhea in the face of rising antimicrobial resistance. (See "Treatment of uncomplicated gonococcal infections", section on 'Monitoring for and managing treatment failure' and "Treatment of uncomplicated gonococcal infections", section on 'Rationale for dual therapy'.)
USPSTF recommendations on syphilis screening in nonpregnant adults and adolescents (June 2016)
In June 2016, the United States Preventive Services Task Force updated its statement on syphilis screening in asymptomatic nonpregnant adolescents and adults to recommend screening for those who are at high risk for infection . These include sexually active men who have sex with men (MSM), HIV-infected patients, and individuals with a history of incarceration or commercial sex work. The optimal frequency of routine screening in high-risk patients without a clear exposure is yet to be determined. Consistent with other expert guidelines, we suggest annual screening for sexually active MSM and HIV-infected individuals, with more frequent screening for those with high-risk behaviors, such as multiple or anonymous sexual partners. (See "Syphilis: Screening and diagnostic testing", section on 'Asymptomatic patients' and "Screening for sexually transmitted infections".)
Shortage of benzathine penicillin G (Bicillin L-A) (May 2016)
In May 2016, the United States Centers for Disease Control and Prevention reported a manufacturing delay of benzathine penicillin G (Bicillin L-A), which is the treatment of choice for all stages of syphilis . In light of potential shortages of this agent, it is important for clinicians to note that only a single dose of benzathine penicillin G is warranted for early syphilis. Pregnant women with syphilis should be prioritized for benzathine penicillin G, and so alternative regimens, such as doxycycline, may need to be used for nonpregnant adults if supplies are limited. Bicillin C-R (equal concentrations of procaine and benzathine penicillin G) should not be used to treat syphilis. (See "Syphilis: Treatment and monitoring", section on 'Penicillin as the treatment of choice'.)
VIRAL INFECTIONS, NON-HIV
Mosquito-borne transmission of Zika virus in the continental United States (August 2016)
Zika virus is a mosquito-borne infection associated with congenital microcephaly and other birth defects among babies born to women infected during pregnancy. Mosquito-borne transmission of Zika virus was detected in Florida in July 2016, and in August 2016 the United States Centers for Disease Control and Prevention (CDC) issued an advisory recommending that pregnant women avoid travel to affected areas . Updates regarding areas with Zika may be found on the CDC website (http://www.cdc.gov/zika/). (See "Zika virus infection: An overview", section on 'Travel advisories for pregnant women'.)
Investigational laboratory test for Zika virus in donated blood (April 2016, Modified August 2016)
A laboratory test that detects Zika virus RNA is under investigation in the United States to screen donated blood for Zika . This test has been implemented under a US Food and Drug Administration (FDA)-approved investigational new drug application (IND) for all blood that is collected in Puerto Rico, a jurisdiction defined by the Centers for Disease Control (CDC) as an active Zika virus transmission area, and in Florida, following reports of mosquito-borne transmission. In areas without active transmission, the donor medical and travel history is used to disqualify individuals who may be infected with Zika. (See "Blood donor screening: Laboratory testing", section on 'Zika virus'.)
Testing for Zika virus infection in pregnant women (July 2016)
The approach to testing for Zika virus infection is different for pregnant versus nonpregnant individuals because Zika virus RNA persists longer in pregnant women’s serum and because pregnant women may transmit the infection to the fetus, even if the mother is asymptomatic. Congenital Zika virus infection can result in serious sequelae. The United States Centers for Disease Control and Prevention recently revised their algorithm for the diagnosis of Zika virus infection in pregnancy to reflect these principles . (See "Zika virus infection: Pregnancy and congenital infection", section on 'Clinical approach'.)
Sofosbuvir-velpatasvir for all genotypes of chronic HCV infection (July 2016)
All-oral, direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have proliferated over the past two years. Sofosbuvir-velpatasvir, a coformulated combination of an NS5B and an NS5A inhibitor, is the first such regimen that has high, well-established efficacy for all genotypes, even in patients with cirrhosis or prior treatment failure with interferon-based regimens [52-54]. This agent was approved by the US Food and Drug Administration in June 2016 and is now our preferred or one of our preferred regimens for adults with chronic HCV infection of any genotype because of its efficacy, simplicity of administration, and limited drug interactions. Sofosbuvir-velpatasvir is given for 12 weeks for all genotypes. For genotype 3 infection, the addition of ribavirin may be warranted, depending on the presence of cirrhosis, the prior treatment history, and the presence of mutations associated with NS5A resistance. (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'.)
Influenza postexposure prophylaxis with inhaled laninamivir (May 2016)
Laninamivir, a long-acting inhaled neuraminidase inhibitor, has been reported to be effective for preventing influenza infection in the household contacts of patients with influenza. In a randomized trial, family members living with a patient with influenza infection within 48 hours of symptom onset were randomly assigned to receive a single dose of laninamivir, two doses of laninamivir given daily for two days, or placebo . The proportion of participants who developed clinical influenza that was confirmed by laboratory testing was significantly lower in the laninamivir groups than in the placebo group. Laninamivir is approved for use in Japan, but remains investigational elsewhere. (See "Prevention of seasonal influenza with antiviral drugs in adults", section on 'General' and "Seasonal influenza in children: Prevention and treatment with antiviral drugs", section on 'Choice of drug'.)
Zika virus and blood donation (March 2016, Modified April 2016)
The blood donor medical and travel history is used to identify and disqualify individuals who may be infected with Zika. Several agencies including the US Food and Drug Administration (FDA), World Health Organization (WHO), and AABB (an international organization) have issued guidance to reduce the risk of transmission in affected and unaffected areas [56-59]. These vary slightly but all include recommendations for deferral of individuals at risk of infection based on travel, symptoms, or sexual contacts, and recall and destruction of products if the donor develops symptoms of infection or diagnosis of Zika following donation. The WHO also recommends consideration of temporarily stopping collections and/or quarantining units until lack of symptoms can be confirmed. Currently used donor questionnaires are likely to identify individuals with symptomatic infection at the time of donation. The FDA has approved two investigational nucleic acid tests for Zika screening. (See "Blood donor screening: Medical history", section on 'Zika virus'.)
Zika virus and tissue/gamete donation (March 2016)
Zika virus has been detected in a number of tissues and body fluids. To avoid possible transmission of Zika virus infection, the US Food and Drug Administration (FDA) has issued donor deferral recommendations for hematopoietic stem cells, tissues, and donor sperm or eggs; the recommendations do not apply to solid organs . Living donors with Zika virus infection or relevant epidemiologic exposure (residence in or travel to an area where mosquito-borne transmission of Zika virus infection has been reported, or unprotected sexual contact with a person who meets these criteria) should be considered ineligible for donation for six months. Deceased donors with Zika virus infection in the preceding six months should also be considered ineligible. The deferral period recommended by the FDA for blood donors with risk factors for Zika virus infection remains at four weeks. (See "Zika virus infection: An overview", section on 'Blood/tissue donation'.)
Zika virus and Guillain-Barre syndrome (March 2016)
Zika virus has been associated with Guillain-Barre syndrome (GBS), although a direct causal relationship has not been definitively established. A case-control study in French Polynesia evaluated the association between GBS and Zika virus infection during the 2013 to 2014 outbreak . Cases included 42 patients diagnosed with GBS; one control group included 98 patients with nonfebrile illnesses and a second control group included 70 patients with Zika virus infection in the absence of neurological complications. Zika IgM was positive in 93 percent of GBS cases (versus 17 percent of patients in the first control group); serologic evidence of past dengue infection was similar among all three groups. Antiglycolipid IgG antibodies were detected in fewer than 50 percent of GBS cases, raising the possibility of direct viral neurotoxicity. Results of nerve conduction studies were consistent with the acute motor axonal neuropathy type of GBS; clinical improvement during follow-up suggested reversible conduction failure. Symptoms of Zika virus infection occurred in 88 percent of patients with GBS; the median interval between viral syndrome and onset of neurological symptoms was six days. All GBS cases received intravenous immune globulin, 38 percent required intensive care, and 29 percent needed respiratory care; all survived. The incidence of GBS during the outbreak was estimated to be 0.24 cases per 1000 Zika virus infections. (See "Zika virus infection: An overview", section on 'Guillain-Barré syndrome'.)
Elbasvir-grazoprevir for chronic HCV infection (February 2016)
Despite the proliferation of interferon-free regimens for the treatment of chronic hepatitis C (HCV) infection, safety concerns have limited options for patients with severe renal impairment, who have been excluded from trials of most available regimens. In January 2016, the US Food and Drug Administration approved the new combination regimen elbasvir-grazoprevir for the treatment of patients with genotypes 1 and 4 HCV infection, including those with any degree of renal impairment (including dialysis dependence) . In a randomized, placebo-controlled trial of genotype 1-infected patients with estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m2, the sustained virologic response (SVR) rate was 94 percent among the 122 patients who received elbasvir-grazoprevir for 12 weeks, and adverse event rates were similar between treatment and placebo groups . These results were comparable to those among patients with normal renal function. Elbasvir-grazoprevir is given for 12 to 16 weeks with or without ribavirin, depending on the presence of pre-existing resistance-associated variants in the NS5A protein and prior exposure to HCV protease inhibitors. (See "Treatment of chronic hepatitis C infection in adults with renal impairment", section on 'Regimens with direct-acting antivirals'.)
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