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What's new in infectious diseases
Official reprint from UpToDate® ©2015 UpToDate®
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What's new in infectious diseases

Disclosures: Elinor L Baron, MD, DTMH Nothing to disclose. Allyson Bloom, MD Nothing to disclose. Anna R Thorner, MD Nothing to disclose. Jennifer Mitty, MD, MPH Nothing to disclose.

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.

Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2015. | This topic last updated: Mar 26, 2015.

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.


Enhanced gram-negative activity of novel beta-lactam/beta-lactamase inhibitor combinations (January 2015, MODIFIED March 2015)

The US Food and Drug Administration recently approved two novel cephalosporin-beta-lactamase inhibitor combinations, ceftazidime-avibactam and ceftolazone-tazobactam, which were developed to treat highly resistant gram-negative infections. These agents have broad-spectrum in vitro activity against aerobic gram-negative rods, including Pseudomonas aeruginosa and most extended-spectrum-beta-lactamase-producing gram negative organisms. Ceftazidime-avibactam also has in vitro activity against some carbapenemase-producing organisms. In as yet unpublished clinical trials, clinical cure rates with these new agents alone or in combination with metronidazole were similar to those with comparator antibiotics for complicated urinary tract and intra-abdominal infections [1-3]. (See "Combination beta-lactamase inhibitors, carbapenems, and monobactams", section on 'Ceftolozane-tazobactam' and "Combination beta-lactamase inhibitors, carbapenems, and monobactams", section on 'Ceftazidime-avibactam'.)

Trimethoprim-sulfamethoxazole and sudden death (December 2014)

While trimethoprim-sulfamethoxazole (TMP-SMX) has generally been felt to be well tolerated, a case-control study found an association between sudden death, possibly due to hyperkalemia, and prescription of TMP-SMX among older patients who were also receiving an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) [4].Those who received TMP-SMX had an increased seven-day risk of sudden death compared with those who received amoxicillin (adjusted odds ratio 1.38, 95% CI 1.09-1.76). However, other factors that affected the choice of antibiotic may have confounded these results, and higher quality evidence is needed to determine whether this association is causal. (See "Trimethoprim-sulfamethoxazole: An overview", section on 'Life threatening effects'.)

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

The role of prophylactic antibiotics in the treatment of patients with acute liver failure is controversial. In a retrospective study of 1551 patients with acute liver failure, antimicrobial prophylaxis did not reduce the incidence of bloodstream infection or mortality [5]. Our approach to antibiotic prophylaxis is to not give patients prophylactic antibiotics, but instead give antibiotics only if there is evidence of active infection, positive surveillance culture results, or clinical deterioration. (See "Acute liver failure in adults: Management and prognosis", section on 'Infection surveillance and prevention'.)

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

The use of prophylactic antibiotics to decontaminate the oropharyngeal and/or digestive tracts of critically ill patients and reduce the risk of infection confers a modest mortality benefit but is not widely used, in part, because of concern that it can promote antimicrobial resistance. A large multicenter cluster-randomized trial in intensive care units in the Netherlands compared resistance rates with selective oropharyngeal decontamination (SOD; antibiotics applied to the oropharynx only) and selective digestive decontamination (SDD; antibiotics applied to the oropharynx and through a nasogastric tube plus a different intravenous antibiotic) [6]. Rates of rectal colonization with highly resistant bacteria were overall lower with SDD than SOD, but colonization with aminoglycoside-resistant gram-negative bacilli increased more over time with SDD than SOD. Given the very low baseline rate of antimicrobial resistance in the Netherlands and the absence of a control group that received no prophylactic antibiotics, these findings do not sufficiently allay concerns about long-term antimicrobial resistance with antibiotic use for decontamination of the gastrointestinal tract. (See "Epidemiology and prevention of infections and antimicrobial resistance in the intensive care unit", section on 'Decontamination of the digestive tract'.)


Pneumonia and long-term cardiovascular risk (February 2015)

Community-acquired pneumonia has been associated with increased short-term risk of cardiac events. In two cohorts of community-dwelling adults, hospitalization for pneumonia was also associated with increased long-term risk of new-onset cardiovascular disease (myocardial infarction, cerebrovascular accident, or fatal coronary heart disease), even after adjusting for traditional cardiovascular risk factors [7]. In one of the cohorts, the risk of cardiovascular events among patients with pneumonia was highest during the first year after hospitalization and remained higher than among controls through 10 years. In the other cohort, the risk of cardiovascular events was elevated during the first two years following pneumonia hospitalization, but not thereafter. (See "Prognosis of community-acquired pneumonia in adults", section on 'Association with cardiovascular events'.)

Infection associated with contaminated endoscopes (October 2014, MODIFIED February 2015)

In January 2014, the Centers for Disease Control and Prevention (CDC) reported that 69 cases of New Delhi metallo-beta-lactamase (NDM)-producing carbapenem-resistant Enterobacteriaceae (CRE) had been identified in the United States (44 from northeastern Illinois) in the previous year [8]. Further investigation identified 39 cases from one hospital [9]. Sporadic cases have been subsequently reported to the US Food and Drug Administration (FDA) [10]. The source of infection has been traced to the elevator channel of a single duodenoscope (the endoscopes used for endoscopic retrograde cholangiopancreatography [ERCP]). No lapses in the cleaning protocol were identified. It is theorized that the complex design of the elevator mechanism makes it more difficult to clean than other parts of endoscopes [9,11]. After changing duodenoscope reprocessing from high-level disinfection to gas sterilization with ethylene oxide, no new cases have been identified. Duodenoscopes should be considered as possible sources for CRE outbreaks in healthcare facilities. If a patient is diagnosed with a multidrug-resistant organism following ERCP, the duodenoscope that was used for the procedure should be removed from service until it is verified to be free of pathogens [12,13]. (See "Endoscope disinfection", section on 'Carbapenem-resistant Enterobacteriaceae'.)

Adjunctive glucocorticoids for hospitalized patients with community-acquired pneumonia (January 2015)

There has been interest in using glucocorticoids as adjunctive therapy to antibiotics in hospitalized patients with community-acquired pneumonia (CAP) in an attempt to reduce the inflammatory response, which is likely to contribute to the morbidity of the disease. There are conflicting data on this approach, but the largest randomized trial suggests a modest benefit. In the trial, which included 785 hospitalized adults with CAP, prednisone 50 mg daily for seven days shortened the time to clinical stability by approximately one day compared with placebo, without an increase in complications [14]. In another randomized trial that included 120 patients in Spain with severe CAP and a high inflammatory response, there was less treatment failure among patients who received methylprednisolone 0.5 mg/kg every 12 hours for five days than in those who received placebo, but no difference in the rate of in-hospital mortality [15]. Pending the results of a larger trial evaluating mortality rates in severe CAP, we do not favor the routine use of adjunctive glucocorticoids in adults with CAP. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Glucocorticoids'.)

Multistate outbreak of listeriosis associated with caramel apples (December 2014)

A multistate outbreak of listeriosis associated with commercially produced prepackaged caramel apples was reported in the United States in December 2014 [16]. Updated case counts, a list of states in which cases have been reported, and guidance from the United States Centers for Disease Control and Prevention (CDC) can be found on the CDC’s website. (See "Epidemiology and pathogenesis of Listeria monocytogenes infection", section on 'Food epidemiology and outbreaks'.)

Prophylactic antibiotics before laparoscopic cholecystectomy (September 2014)

Multiple meta-analyses of randomized trials comparing antibiotic prophylaxis with no antibiotic or placebo prior to elective laparoscopic cholecystectomy have found no differences in the incidence of surgical site infection. These trials have generally included 50 to 175 patients in each arm and have used a single dose of antibiotics administered just prior to surgery. A subsequent large trial randomly assigned approximately 1000 low-risk patients undergoing elective laparoscopic cholecystectomy to no antibiotics or intravenous antibiotics given preoperatively and at 12 and 24 hours postoperatively [17]. In this later trial, the incidence of surgical site infection was lower for those who received perioperative antibiotics (0.8 versus 3.7 percent without antibiotics). Despite the added cost of antibiotic administration, overall hospital costs were lower in the prophylaxis group. Further investigation is needed to determine whether the infectious risk reduction of additional antibiotic doses outweighs the risks of toxicity or bacterial drug resistance associated with increased antibiotic usage. (See "Laparoscopic cholecystectomy", section on 'Antibiotics'.)


FDA approval of isavuconazole for invasive aspergillosis and mucormycosis (March 2015)

Isavuconazole was approved by the US Food and Drug Administration in March 2015 for the treatment of invasive aspergillosis and mucormycosis [18]. It is formulated as the prodrug, isavuconazonium sulfate, and it is available as an IV formulation and an oral formulation [19]. For patients with invasive aspergillosis who do not tolerate the first-line antifungal agent, voriconazole, we use either a lipid formulation of amphotericin B or isavuconazole in place of voriconazole. For patients with mucormycosis, isavuconazole can be used as an alternative to posaconazole for step-down therapy or salvage therapy in patients who do not tolerate posaconazole. (See "Pharmacology of azoles", section on 'Isavuconazole' and "Treatment and prevention of invasive aspergillosis" and "Treatment and prevention of invasive aspergillosis", section on 'Initial therapy' and "Mucormycosis (zygomycosis)", section on 'Approach to treatment'.)

Voriconazole plus anidulafungin for invasive aspergillosis (January 2015)

Voriconazole has been the first-line therapy for invasive aspergillosis for several years, but mortality remains substantial. A randomized trial assessed voriconazole with or without a second antifungal agent, anidulafungin (an echinocandin), for the treatment of invasive aspergillosis in patients with hematologic malignancy and/or hematopoietic cell transplant [20]. Results showed a non-significant trend toward improved six-week survival with the combination of voriconazole and anidulafungin compared with voriconazole monotherapy. A post-hoc analysis suggested that the survival benefit was statistically significant among a major subset of patients with probable invasive aspergillosis, defined as radiographic abnormalities and a positive galactomannan antigen. Based on these results, we favor the use of a combination regimen of voriconazole plus an echinocandin for the first one to two weeks of therapy of confirmed invasive aspergillosis. However, some experts remain uncertain about these data and prefer monotherapy with voriconazole. (See "Treatment and prevention of invasive aspergillosis", section on 'Voriconazole and an echinocandin'.)

T2Candida assay for the detection of candidemia (September 2014)

In 2014, the US Food and Drug Administration (FDA) cleared the T2Candida assay for the detection of bloodstream infection caused by C. albicans, C. tropicalis, C. parapsilosis, C. glabrata, and/or C. krusei [21]. The T2Candida test uses magnetic resonance technology to detect these pathogens from a blood specimen within three to five hours, but a specialized instrument is required to perform the assay. It has a sensitivity of 84 to 96 percent and a specificity of nearly 100 percent [21,22]. The clinical utility of this technique requires further study. (See "Clinical manifestations and diagnosis of candidemia and invasive candidiasis in adults", section on 'T2Candida'.)


Yaws eradication (February 2015)

Yaws is a treponemal infection that can cause destructive skin and bone lesions and is endemic to rural, equatorial regions in the Eastern Hemisphere. The approach to eradication of yaws consists of a single dose of oral azithromycin (30 mg/kg, maximum 2 g) to be given to the entire population in areas known to harbor yaws [23]. The efficacy of this approach was demonstrated in a study of mass treatment performed in rural villages on Lihir Island, Papua New Guinea [24]. Of 16,092 residents, 83 percent received mass treatment with single dose azithromycin and were monitored for one year; the prevalence of active yaws decreased from 2.4 to 0.3 percent, and the prevalence of latent yaws with high-titer seroreactivity decreased from 18.3 to 6.5 percent. There was a near-absence of high-titer seroreactivity among children 1 to 5 years of age. No evidence of macrolide resistance was observed. (See "Yaws, bejel, and pinta", section on 'Eradication'.)

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

No licensed vaccine is available for preventing dengue; thus far CYD-TDV, a live attenuated tetravalent vaccine, is the most promising. Two large trials were published in 2014 evaluating the efficacy of the vaccine. In these randomized, placebo-controlled trials, conducted in over 30,000 children in the Asia-Pacific region, Latin America, and the Caribbean, the vaccine efficacy of three CYD-TDV doses against virologically confirmed dengue was 57 to 61 percent in the intention-to-treat analyses [25,26]. The vaccine efficacy against dengue hemorrhagic fever after three doses was 89 to 95 percent. Therefore, this vaccine is most effective for protection against severe disease. Vaccine efficacy varied by serotype, and was least protective against serotype 2. The epidemiologic threshold of dengue activity upon which national vaccination programs are justified has yet to be determined. (See "Prevention and treatment of dengue virus infection", section on 'Vaccination'.)


Kidney transplantation from HIV-positive deceased donors into HIV-positive recipients (February 2015)

As is the case for most other patients with end stage renal disease (ESRD), kidney transplantation is superior to other forms of renal replacement therapy for HIV-positive patients with ESRD. In countries where dialysis is a limited resource, kidney transplantation is life-saving. However, kidney transplantation is limited by a shortage of available organs. In a case series from South Africa, 27 carefully selected and treated HIV-positive patients underwent transplantation with kidneys from HIV-positive deceased donors [27]. Patient and allograft survival at 1, 3 and 5 years was comparable to reported patient and allograft survival of HIV-positive patients who received kidneys from HIV-negative donors. (See "Solid organ transplantation in HIV-infected individuals", section on 'Renal transplantation'.)

HIV infection and chronic kidney disease (February 2015)

The HIV Medicine Association of the Infectious Diseases Society of America has updated its guidelines for the management of chronic kidney disease in patients infected with HIV [28]. They recommend screening for kidney disease with serum creatinine measurement and urinalysis at baseline and during use of antiretroviral therapy. The guidelines also discuss indications for nephrology referral and selection of antiretroviral regimens in the setting of renal impairment. The discussion in UpToDate is generally consistent with these guidelines. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient", section on 'Tenofovir-emtricitabine' and "Overview of kidney disease in HIV-positive patients" and "Primary care of the HIV-infected adult".)

Timing of antiretroviral initiation during pregnancy (January 2015)

The risk of HIV transmission from an infected mother to her infant is proportional to the level of maternal viremia at delivery. Among women not already taking an antiretroviral regimen, viral suppression at delivery is more likely when a regimen is initiated earlier during gestation. In a large US cohort of antiretroviral-naïve HIV-infected women who initiated a combination antiretroviral regimen during pregnancy, a detectable viral load at delivery was documented in 13 percent overall, but in 24 percent of those who initiated the regimen during the third trimester [29]. This supports our recommendation to initiate antiretroviral therapy promptly in treatment-naïve pregnant women with advanced HIV disease or CD4 cell count th week of gestation for HIV-infected pregnant women with higher CD4 cell counts. (See "Use of antiretroviral medications in pregnant HIV-infected patients and their infants in resource-rich settings", section on 'When to initiate antiretroviral medications during pregnancy'.)

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

In resource-limited settings, the choice of an antiretroviral regimen for HIV infection following virologic failure with an initial regimen must often be made without knowledge of the presence of resistance mutations. There has been concern that drug resistance following failure of a nucleoside reverse transcriptase inhibitor (NRTI) based regimen would render subsequent NRTI-based regimens less effective. However, in a trial from sub-Saharan Africa that included 1277 HIV-infected individuals who had failed treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two NRTIs, rates of virologic suppression were similar with a boosted protease inhibitor plus two to three NRTIs or plus an integrase inhibitor (88 and 87 percent, respectively) [30]. Virologic suppression rates with boosted protease inhibitor monotherapy were lower. These data support the World Health Organization recommendations to use a boosted protease inhibitor with at least two NRTIs as a second line regimen in resource limited settings. (See "The impact of antiretroviral therapy on morbidity and mortality of HIV infection in resource-limited settings", section on 'Drug resistance'.)


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

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


Circulating influenza A H3N2 viruses and influenza vaccine effectiveness in the United States (December 2014, MODIFIED March 2015)

In December 2014, the United States Centers for Disease Control and Prevention (CDC) released a health advisory stating that more than half of influenza A H3N2 viruses collected and analyzed in the United States in October and November 2014 were antigenically different (drifted) from the H3N2 antigen included in this season's influenza vaccines [32]. Most isolated influenza viruses to date have been H3N2 strains. During previous seasons in which influenza A H3N2 viruses have predominated, higher hospitalization and mortality rates have been reported among older people, very young children, and individuals with certain medical conditions. In seasons where predominant circulating influenza viruses have antigenically drifted, decreased vaccine effectiveness has been observed. Nevertheless, vaccination typically provides some cross-protection against drifted viruses and should still reduce hospitalization and death. As of late February 2015, overall vaccine effectiveness was only 19 percent and vaccine effectiveness against influenza A H3N2 was only 18 percent [33]. Influenza vaccination is still highly recommended [32]. The CDC health advisory was issued to reemphasize the importance of the use of neuraminidase inhibitors (eg, oseltamivir, zanamivir) when indicated for the treatment and prevention of influenza infection as an adjunct to vaccination. (See "Seasonal influenza vaccination in adults", section on 'Drifted H3N2 viruses during the 2014 to 2015 influenza season' and "Seasonal influenza in children: Prevention with vaccines", section on 'Drifted H3N2 viruses during the 2014 to 2015 influenza season'.)

Pneumococcal conjugate vaccine in adults ≥65 years of age (September 2014, MODIFIED March 2015)

The CAPiTA trial, which is the largest trial to assess the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13) in adults, compared PCV13 to placebo in approximately 85,000 immunocompetent adults ≥65 years of age in the Netherlands who had not received a pneumococcal vaccine previously [34]. The trial demonstrated 46 percent efficacy of PCV13 against vaccine-type pneumococcal pneumonia, 45 percent efficacy against vaccine-type nonbacteremic pneumococcal pneumonia, and 75 percent efficacy against vaccine-type invasive pneumococcal disease. Efficacy persisted for the duration of the trial (mean follow-up four years). However, some concern has been raised that since this trial began before PCV13 was used routinely in infants in the Netherlands, it might not answer the question of whether its use in adults is efficacious in countries that routinely vaccinate infants. (See "Pneumococcal vaccination in adults", section on 'Efficacy'.)

The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for many years in the United States for all adults ≥65 years of age. In September 2014, the United States Advisory Committee on Immunization Practices (ACIP) began also recommending PCV13 for all adults ≥65 years of age [35]. The ACIP revision was prompted by results from the CAPiTA trial. Current recommendations for individuals ≥65 years of age who have not previously received either PCV13 or PPSV23 are to administer PCV13 followed 6 to 12 months later by PPSV23 (algorithm 1). In patients who have already received PPSV23, at least one year should elapse before they are given PCV13. (See "Pneumococcal vaccination in adults", section on 'Indications'.)

New human papillomavirus (HPV) vaccine targets nine HPV types (February 2015)

Infection with human papillomavirus (HPV) types 16, 18, 31, 33, 45, 52, and 58 is implicated in approximately 90 percent of invasive cervical cancers. The US Food and Drug Administration has approved Gardasil 9, a 9-valent HPV vaccine that targets those seven HPV types in addition to the two types associated with genital warts (6 and 11), for the prevention of HPV-related disease [36]. In a trial that included approximately 14,000 females randomly assigned to receive the 9-valent or quadrivalent HPV vaccine, immune responses with the two vaccines were comparable for the HPV types targeted by both (6, 11, 16, and 18). Additionally, the 9-valent HPV vaccine was 97 percent effective for preventing precancerous and cancerous lesions of the cervix, vagina, and vulva associated with the other targeted HPV types (31, 33, 45, 52, and 58). Safety profiles were overall similar. We favor the 9-valent HPV vaccine for its broader HPV type coverage.

Routine immunization should be offered to boys and girls aged 11 to 12, but can be administered as early as nine years of age. Catch-up vaccination should be offered for males between the ages of 13 to 21 and females between 13 to 26 years who have not been previously vaccinated. Repeat vaccination with the 9-valent vaccine is likely not warranted for individuals who have completed a series with a different HPV vaccine.

(See "Recommendations for the use of human papillomavirus vaccines", section on 'Available vaccines'.)

No association between HPV vaccination and multiple sclerosis (January 2015)

Although anecdotal and sporadic case reports had fueled concerns about a potential causal relationship between human papillomavirus (HPV) vaccination and development of multiple sclerosis and other demyelinating disorders, larger studies have refuted this. In a study of nearly four million Swedish and Danish females aged 10 to 44 years, receipt of the quadrivalent HPV vaccine was not associated with demyelinating diseases, including multiple sclerosis, optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis [37]. This study adds to the abundance of data demonstrating the overall safety of HPV vaccination. (See "Recommendations for the use of human papillomavirus vaccines", section on 'Postlicensure data'.)

FDA approval of meningococcal serogroup B vaccines (October 2014, MODIFIED January 2015)

Neisseria meningitidis serogroup B is responsible for approximately one-third of cases of meningococcal disease in the United States and has caused outbreaks on college campuses in the recent past. Previously licensed meningococcal vaccines in the United States do not protect against serogroup B. In October 2014, the US Food and Drug Administration approved a serogroup B meningococcal vaccine (Trumenba) for use in individuals 10 through 25 years of age [38]. In January 2015, the FDA approved another serogroup B meningococcal vaccine (Bexsero) for use in individuals 10 through 25 years of age [39]. In February 2015, the United States Advisory Committee on Immunization Practices voted to recommend a serogroup B meningococcal vaccine for high-risk individuals aged 10 years or older, but formal recommendations have not yet been released [40]. (See "Meningococcal vaccines", section on 'In children and adolescents' and "Meningococcal vaccines", section on 'Group B meningococcus vaccines'.)


Sputum Xpert MTB/RIF for discontinuation of TB airborne isolation (February 2015)

Serial acid-fast bacilli (AFB) sputum smears are traditionally used to assess the need for continued airborne infection isolation for patients with suspected tuberculosis, and airborne precautions can generally be discontinued if three serial AFB smear are negative. In February 2015, the US FDA approved the use of the Xpert MTB/RIF assay, a nucleic acid amplification test that detects Mycobacterium tuberculosis (MTB), as an alternative to serial AFB smears for this purpose [41,42]. This approval was based on a study demonstrating that sputum Xpert MTB/RIF results are highly predictive of AFB smear results and may require fewer sputum samples [43]. Xpert MTB/RIF assay testing on a single sputum sample detected MTB in approximately 97 percent of patients who had at least one positive result on two or three serial fluorescent-stained AFB sputum smears and were subsequently culture-confirmed as infected with MTB. Xpert MTB/RIF assay testing on two serial sputum samples detected 100 percent of AFB smear–positive/MTB culture-positive patients. (See "Diagnosis of pulmonary tuberculosis in HIV-negative patients", section on 'Xpert MTB/RIF assay' and "Tuberculosis transmission and control".)

Isoniazid and rifapentine for treatment of latent tuberculosis infection in children (February 2015)

Isoniazid (INH) is the regimen of choice for the treatment of latent tuberculosis infection in children, but full adherence throughout the nine-month course can be challenging. A study among 1058 children ages 2 to 17 years demonstrated that directly observed treatment with three months of INH and rifapentine (RPT) was as effective as nine months of unsupervised INH alone for prevention of tuberculosis [44]. Treatment related adverse events were uncommon and similar with the two regimens. Directly observed treatment with INH-RPT is a reasonable regimen for children aged 2 to 17 years when the circumstances make completion of nine months of daily INH difficult. (See "Latent tuberculosis infection in children", section on 'Isoniazid and rifapentine'.)

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

Because of their highly bactericidal activity against Mycobacterium tuberculosis, the use of fluoroquinolones in an antituberculous regimen has been hypothesized to allow a shorter duration of treatment. However, shortening treatment with a moxifloxacin-containing regimen to four months was not effective in a phase III trial that included 1931 patients with uncomplicated, smear-positive pulmonary tuberculosis. The study demonstrated that each of two moxifloxacin-containing regimens (isoniazid, rifampin, pyrazinamide, and moxifloxacin; or rifampin, pyrazinamide, ethambutol, and moxifloxacin) given for 17 weeks resulted in greater treatment failure and relapse compared with the standard control regimen of two months of isoniazid, rifampin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampin [45]. This was despite shorter times to negative sputum cultures with the moxifloxacin regimens than the control regimen. Subsequent studies using gatifloxacin as the fluoroquinolone or moxifloxacin in combination with other antituberculous agents similarly demonstrated worse outcomes with a shorter four-month regimen [46,47]. (See "Treatment of pulmonary tuberculosis in HIV-negative patients", section on 'Fluoroquinolones'.)


Cerebral malaria and elevated intracranial pressure (March 2015)

Cerebral malaria is an encephalopathy that presents with impaired consciousness, delirium, and/or seizures. Cerebral edema and elevated intracranial pressure may contribute to a fatal outcome. In one study that included 168 children with cerebral malaria, approximately 84 percent of deaths occurred among individuals with evidence of severe brain swelling on MRI at admission; such swelling was noted among 27 percent of survivors [48]. (See "Clinical manifestations of malaria", section on 'Cerebral malaria'.)


Possible association of giant cell arteritis with varicella zoster virus (March 2015)

The etiology of giant cell arteritis (GCA) remains unknown, although various infectious causes have been considered as triggering events. One of the largest studies to evaluate the relationship between varicella zoster virus (VZV) and GCA included temporal artery (TA) biopsies from 82 pathologically-confirmed GCA patients and 13 TA biopsies from healthy controls [49]. VZV antigen was found in 74 percent of pathologically-confirmed GCA TAs versus 8 percent of normal TAs. The majority of biopsies showing GCA contained VZV antigen in skip areas that correlated with adjacent GCA pathology. However, direct pathogenetic evidence of a causal role of VZV in GCA is lacking. (See "Pathogenesis of giant cell (temporal) arteritis", section on 'Etiology and pathogenesis'.)

Interferon-free regimens to treat HCV in HIV/HCV coinfected patients (February 2015)

Patients coinfected with HIV and hepatitis C virus (HCV) traditionally had lower response rates to HCV treatment with peginterferon and ribavirin compared with individuals without HIV infection. However, with the use of direct-acting antiviral (DAA) agents in HCV treatment, HIV infection is no longer a negative predictor of response. In two studies of HIV/HCV genotype 1 coinfected individuals, sustained virological response rates to two interferon-free DAA regimens (ledipasvir-sofosbuvir or ombitasvir-paritaprevir-ritonavir and dasabuvir plus ribavirin) were greater than 90 percent, comparable to rates in populations infected with HCV alone [50,51]. The major consideration in HCV antiviral regimen selection for HIV/HCV coinfected patients is the potential for drug interactions between antiretroviral and HCV antiviral agents. (See "Treatment of hepatitis C virus infection in the HIV-infected patient", section on 'Genotype 1 infection'.)

Measles outbreak in United States (February 2015)

The United States has experienced a record number of measles cases during 2014 to 2015. In 2014, 644 cases were reported from 27 states [52]. During just the first month of 2015, an additional 121 cases from seven states were reported. Most of these cases are part of an ongoing multistate outbreak linked to an amusement park in California [53]. Most cases have occurred among individuals who were unvaccinated. Children living in or traveling to areas where there is a measles outbreak (defined as ≥3 cases linked in time and space) and children traveling outside the United States should receive measles-mumps-rubella vaccine earlier than it is routinely recommended. (See "Epidemiology and transmission of measles", section on 'United States' and "Standard immunizations for children and adolescents", section on 'Outbreaks and international travel'.)

Preventing hepatitis B virus reactivation in patients receiving chemotherapy (February 2015)

When patients with serologic evidence of hepatitis B virus (HBV) infection need immunosuppressive therapy for other reasons, antiviral therapy may be warranted to decrease the risk of HBV reactivation. We favor prophylaxis with entecavir or tenofovir over lamivudine in such cases because these agents have more potent antiviral activity and are less likely to select for drug resistant virus. This preference is supported by results of a trial in which 121 HBV surface antigen (HBsAg) positive patients were randomly assigned to prophylactic antiviral therapy with entecavir or lamivudine prior to receiving chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for diffuse large B-cell lymphoma [54]. The rates of HBV-related hepatitis and HBV reactivation were lower among those who received entecavir. (See "Hepatitis B virus reactivation associated with immunosuppressive therapy", section on 'Which agents to use'.)

Oseltamivir for the treatment of influenza in adults (January 2015)

Oseltamivir has been demonstrated to shorten the duration of influenza symptoms and to reduce the duration of viral shedding. However, studies and meta-analyses have provided contradictory results regarding the effect of oseltamivir on influenza-related lower respiratory tract complications in healthy adults. A 2015 meta-analysis evaluated all manufacturer-sponsored randomized trials, published and unpublished, of oseltamivir for the treatment of influenza in adults [55]. Among those with documented influenza, oseltamivir reduced the time to alleviation of all symptoms (median time 98 versus 123 hours), reduced lower respiratory tract complications requiring antibiotics, and reduced hospital admissions for any cause compared with placebo. In contrast to an earlier meta-analysis that aggregated study results and did not demonstrate a benefit with regards to complications, this meta-analysis pooled individual patient data from the trials, which is generally considered a more rigorous method [56]. These results support our recommendations to use an antiviral agent such as oseltamivir in patients with confirmed or suspected influenza and severe illness or at high risk of complications. (See "Treatment of seasonal influenza in adults", section on 'Efficacy of oseltamivir'.)

Rapid nucleic acid amplification test for seasonal influenza (January 2015)

A rapid nucleic acid amplification test for influenza, the Alere i influenza A & B test, is available in several countries in Europe. In January 2015, the US Food and Drug Administration allowed use of the test in non-traditional laboratory sites, including physicians' offices, emergency rooms, health department clinics, and other healthcare facilities [57]. This test uses a nasal swab sample and provides results (reports influenza A or B, but not subtypes) in as few as 15 minutes. It is performed on a small proprietary machine. Nucleic acid amplification tests are generally more sensitive than antigen and immunofluorescence techniques, which most other rapid influenza tests utilize. (See "Diagnosis of seasonal influenza in adults", section on 'Nucleic acid tests' and "Seasonal influenza in children: Clinical features and diagnosis", section on 'Approach to testing'.)

Late cytomegalovirus prophylaxis versus preemptive therapy following hematopoietic cell transplantation (January 2015)

During the early postengraftment period following allogeneic hematopoietic cell transplantation (HCT), preemptive strategies are employed more commonly than prophylactic strategies to prevent cytomegalovirus (CMV) disease. Optimal preventive strategies during the late postengraftment period (days 100 to 270) have been uncertain. In a multicenter trial, allogeneic HCT recipients at high risk for late CMV disease were randomly assigned to receive six months of valganciclovir prophylaxis or placebo at a median of approximately 97 days after HCT [58]. Plasma CMV levels were monitored weekly and the study drug was replaced by preemptive antiviral therapy if the CMV viral load increased above a certain threshold. Although fewer patients receiving valganciclovir prophylaxis warranted preemptive therapy (11 versus 36 percent of placebo recipients), the primary composite endpoint (death, CMV disease, or other invasive bacterial or fungal infections by 270 days after HCT) occurred at similar frequencies in both groups (20 and 21 percent). These results suggest that routine prophylaxis during the late postengraftment period is not warranted; however, it is prudent to monitor the CMV load in the blood in high-risk patients and initiate preemptive therapy if it becomes positive. (See "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Late postengraftment'.)

Interferon-free regimens for chronic genotype 1 HCV infection (December 2013, MODIFIED January 2015)

Several highly effective and well tolerated interferon-free options are now available for chronic genotype 1 hepatitis C virus (HCV) infection. Ledipasvir-sofosbuvir, ombitasvir-paritaprevir-ritonavir plus dasabuvir, and simeprevir plus sofosbuvir all achieve sustained virologic response (SVR) rates, and thus effective cure, in excess of 90 percent in genotype 1 infected patients [59-67]. The duration of the regimen and the decision of whether to add weight-based ribavirin depend on the treatment history, presence of cirrhosis, and, for the ombitasvir-paritaprevir-ritonavir plus dasabuvir regimen, the infecting subtype (1a or 1b) (algorithm 2). The choice between the regimens depends primarily on the potential for drug interactions and drug toxicity. Additionally, in the United States, options will be limited by the individual's insurance provider. If cost or insurance coverage is not an issue, we generally favor the regimen of ledipasvir-sofosbuvir for its favorable adverse effect profile, its minimal drug interactions, and its ease of administration (a single pill once daily). (See "Treatment regimens for chronic hepatitis C virus genotype 1", section on 'Selection of treatment regimens'.)

Intravenous peramivir for influenza (December 2014)

Peramivir was approved by the US Food and Drug Administration (FDA) in December 2014 for treating uncomplicated influenza infection in adults who have been ill for ≤2 days [68,69]. Peramivir is the first IV neuraminidase inhibitor to be approved by the FDA, although it has been in use in Japan and South Korea for several years. It is administered as a single intravenous dose of 600 mg. In a randomized trial, those who received peramivir had their influenza symptoms alleviated an average of 21 hours sooner and became afebrile approximately 12 hours sooner than those who received placebo. Patients who cannot receive zanamivir or oseltamivir (eg, those who cannot tolerate inhaled or enteral agents) should receive IV peramivir. Although the FDA has only approved IV peramivir for patients with uncomplicated influenza, we think it is also reasonable to use it for patients with severe influenza who cannot receive oral oseltamivir or inhaled zanamivir; in such patients, we would use either oseltamivir by a nasogastric tube or IV peramivir. (See "Treatment of seasonal influenza in adults", section on 'Efficacy of peramivir' and "Treatment of seasonal influenza in adults".)

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

Recurrence of hepatitis C virus (HCV) following liver transplantation occurs in more than 95 percent of patients who fail to have the virus eradicated prior to transplantation. Current treatment regimens using direct-acting antiviral agents such as sofosbuvir and simeprevir are based largely on studies in patients with HCV who have not undergone liver transplantation. Treatment of patients with HCV recurrence after liver transplantation with direct-acting antiviral agents was recently examined in a study with 34 patients [70]. The patients were given ombitasvir (an NS5A inhibitor), ritonavir-boosted paritaprevir (a protease inhibitor), dasabuvir (a nonnucleoside NS5B polymerase inhibitor), and ribavirin for 24 weeks. A sustained virologic response at 24 weeks was achieved by 97 percent of patients, with no episodes of graft rejection. This study supports the use of direct-acting antiviral agents in patients with HCV recurrence following liver transplantation. (See "Liver transplantation for hepatitis C virus infection", section on 'Other regimens'.)


Revised name and diagnostic criteria for chronic fatigue syndrome (February 2015)

Diagnostic criteria for chronic fatigue syndrome have been revised (table 1) by the Institute of Medicine (IOM), which has also suggested renaming the condition as systemic exertion intolerance disease (SEID) [71]. The IOM diagnostic criteria focus on the most specific features of the disease. Symptoms should be present for at least six months and have moderate, substantial, or severe intensity at least one-half of the time. Other criteria include post-exertional malaise, sleep problems, cognitive impairment, and orthostatic-related symptoms. (See "Clinical features and diagnosis of chronic fatigue syndrome (systemic exertion intolerance disease)", section on 'Definition'.)

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