[UpToDate] What's new in infectious diseases

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What's new in infectious diseases
Authors
Elinor L Baron, MD, DTMH
Allyson Bloom, MD
Anna R Thorner, MD
Jennifer Mitty, MD, MPH


Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2013. | This topic last updated: 七月 2, 2013.

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.

ANTIMICROBIAL AGENTS

Azithromycin and cardiovascular mortality

In a large cohort study that used Danish national healthcare data to evaluate the association between azithromycin use and cardiovascular death in young and middle-aged adults, the risk of death from cardiovascular causes was significantly increased with current use of azithromycin compared with no use of antibiotics [1]. However, in an adjusted analysis, current azithromycin use was not associated with an increased risk of cardiovascular death compared with penicillin V, suggesting that the increased risk was attributable to underlying patient factors that led to the prescription of antibiotics.

In 2013, the US Food and Drug Administration issued a warning about the risk of QT interval prolongation and potentially fatal torsades de pointes among patients taking azithromycin [2]. The warning was based on a review that followed the publication of a study that showed an increased risk of cardiovascular mortality and all-cause mortality in Medicaid patients receiving azithromycin compared with amoxicillin or no antibiotics [3].

Of note, the population in the Danish study was healthier than the Medicaid population in the earlier analysis. The current study suggests that azithromycin does not increase the risk of cardiovascular death in young and middle-aged persons without preexisting cardiovascular disease. (See "Azithromycin, clarithromycin, and telithromycin", section on 'QT interval prolongation'.)

Tedizolid

Tedizolid is a novel oxazolidinone drug that is noninferior to linezolid for the treatment of acute bacterial skin and skin structure infections in early clinical response (48 to 72 hours after initiating therapy) [4]. Among 667 adults randomized to receive tedizolid or linezolid, early response rates were 79.5 and 79.4 percent, respectively; sustained treatment response rates (day 11) were 69.3 and 71.9 percent, respectively. S. aureus was isolated in more than 80 percent of patients with a positive culture; MRSA was isolated from more than 40 percent of positive cultures. In contrast to linezolid, tedizolid is administered once daily. The safety profiles, including hematologic toxicities, were comparable between the groups. Thus far tedizolid is not available for use in the United States and has not received approval from the US  Food and Drug Administration. (See "Treatment of skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus in adults", section on 'Linezolid or tedizolid'.)

BACTERIAL INFECTIONS

Prophylactic antibiotics for recurrent lower extremity cellulitis

Management of recurrent lower extremity cellulitis can be a challenging problem, and the efficacy of prophylactic antibiotics is uncertain. In a randomized trial of 274 patients with two or more episodes of lower extremity cellulitis, penicillin (250 mg orally twice daily) nearly halved the risk of recurrence during 12 months of prophylaxis, although the protective effect diminished rapidly once the antibiotic was discontinued [5]. Response rates were somewhat lower in patients at highest risk for recurrent cellulitis, such as those with a BMI ≥33, multiple previous episodes of cellulitis, or lymphedema of the leg. (See "Cellulitis and erysipelas", section on 'Recurrent cellulitis'.)

Intravenous albumin for the prevention of hepatorenal syndrome

Several trials have suggested that, in patients with spontaneous bacterial peritonitis (SBP), the administration of intravenous albumin (1.5 g/kg) at the time that the infection is diagnosed and another dose of albumin (1 g/kg) on day three of antibiotic treatment may improve outcomes. In a meta-analysis of four controlled trials (with a total of 288 patients), albumin infusion (in addition to antibiotics) significantly decreased the incidence of renal impairment (8 versus 31 percent) and mortality (16 versus 35 percent) compared with antibiotics alone [6]. (See "Hepatorenal syndrome", section on 'Prevention'.)

S. aureus bacteremia and bedside infectious disease consultation

Bedside infectious disease consultation for patients with S. aureus bacteremia is associated with lower rates of treatment failure, relapse, and mortality. A recent retrospective study compared bedside with telephone infectious disease consultation for management of 342 patients with S. aureus bacteremia [7]; bedside consultation was associated with significantly lower 90-day mortality (1 percent for those who received consultation versus 8 percent for those who did not). Whenever feasible, patients with S. aureus bacteremia should have a bedside infectious disease consultation. (See "Treatment of Staphylococcus aureus bacteremia in adults", section on 'Antimicrobial therapy'.)

Chlorhexidine bathing for intensive care and hematopoietic cell transplant patients

Use of antiseptic agents for patient bathing has been demonstrated to reduce the rate of hospital-acquired bloodstream infections and the risk of colonization with drug-resistant organisms. The greatest efficacy has been demonstrated with chlorhexidine gluconate, an antiseptic agent with broad-spectrum activity. Among more than 7000 patients in intensive care and hematopoietic cell transplant units randomly assigned to bathing with either 2 percent chlorhexidine-impregnated washcloths or nonantimicrobial washcloths for a six-month period (followed by crossover for the alternate product for the subsequent six months), chlorhexidine bathing was associated with reduction in the rate of hospital-acquired bloodstream infections by 28 percent and reduction in the rate of colonization with drug-resistant organisms by 23 percent [8]. (See "General principles of infection control", section on 'Patient bathing'.)

Fecal microbiota transplant for Clostridium difficile infection

Approximately 25 percent of patients with Clostridium difficile (C. difficile)-associated diarrhea have recurrent disease after an initial course of antibiotic therapy. In an open label randomized controlled trial, 43 patients with recurrent C. difficile infection after at least one course of antibiotic therapy were randomly assigned to one of three treatment arms: duodenal infusion of donor feces preceded by an abbreviated regimen of vancomycin (vancomycin 500 mg four times daily for four days) and bowel lavage; a standard vancomycin regimen (vancomycin 500 mg four times daily for 14 days); or a standard vancomycin regimen with bowel lavage [9]. A single infusion of donor feces resulted in significantly higher rates of resolution of C. difficile-associated diarrhea without relapse at 10 weeks as compared with a standard vancomycin regimen with or without bowel lavage (81, 23, and 31 percent, respectively). (See "Fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection", section on 'Administration via nasogastric tube'.)

Raxibacumab for inhalation anthrax

Raxibacumab, a monoclonal antibody directed against Bacillus anthracis protective antigen, was found to be effective for the treatment and prevention of anthrax in randomized trials in animals [10,11]. In phase 2 safety studies in humans, the levels of the antibody achieved in humans are equal to or greater than those that provide protection in animal models [12]. In 2012, raxibacumab was approved by the US Food and Drug Administration for the treatment of inhalation anthrax (in combination with antibiotics) and for the prevention of inhalation anthrax when alternative preventive therapies are not available or are not appropriate [13,14]. A supply of raxibacumab is held in the United States Strategic National Stockpile for use by the Centers for Disease Control in the event of an anthrax emergency. (See "Treatment of anthrax", section on 'Raxibacumab' and "Prevention of anthrax", section on 'Raxibacumab and other immunotherapeutics'.)

FUNGAL INFECTIONS

Vigilance for spinal and paraspinal infections associated with contaminated methylprednisolone

A multistate outbreak of fungal central nervous system infection and septic arthritis was detected in the United States in September 2012. To determine whether patients who had not presented for medical care but who had received contaminated methylprednisolone developed spinal or paraspinal infections at the injection site, screening spine MRIs were performed in patients who had received a highly contaminated lot [15]. Of the 172 patients screened, MRI was abnormal in 36 patients (21 percent), showing epidural or paraspinal abscess or phlegmon, arachnoiditis, spinal osteomyelitis, discitis, or moderate to severe epidural, paraspinal, or intradural enhancement. All but one of the patients with an abnormal MRI met the Centers for Disease Control and Prevention (CDC) case definition for probable or confirmed fungal spinal or paraspinal infection. These data support an earlier recommendation (March 2013) from the CDC that clinicians remain vigilant for fungal infections both in exposed patients who have not previously been evaluated and in those with a previous negative evaluation [16,17]. (See "Outbreak of fungal central nervous system and osteoarticular infections in the United States: Epidemiology, clinical manifestations, and diagnosis", section on 'Injection site infections'.)

Amphotericin B plus flucytosine for cryptococcal meningitis

A randomized open-label trial compared three different induction therapy regimens (amphotericin B deoxycholate as monotherapy, or combined with either flucytosine or fluconazole) for cryptococcal meningitis in HIV-infected patients in Vietnam [18]. Amphotericin B plus flucytosine resulted in decreased mortality and increased clearance rates of yeast from the cerebrospinal fluid compared with the other regimens. Mortality rates were similar for amphotericin B plus fluconazole and amphotericin B monotherapy. The superiority of combination therapy with amphotericin B plus flucytosine in this trial strongly supports the recommendation to use this regimen for induction therapy of cryptococcal meningitis [19]. (See "Treatment of cryptococcal meningoencephalitis in HIV-infected patients", section on 'Induction and consolidation therapy'.)

HIV INFECTION

USPSTF recommendations for universal HIV screening

The United States Preventive Services Task Force (USPSTF) has expanded its recommendations for HIV testing and now recommends that clinicians screen adolescents and adults aged 15 to 65 years for HIV infection [20]. Younger adolescents and older adults who are at increased risk for infection, as well as all pregnant women, should also be screened. These recommendations are based on growing evidence that early detection leads to reduced risk for AIDS-related events or death. Universal screening has previously been endorsed by several other organizations, including the Centers for Disease Control and the American College of Physicians. (See "Serologic screening for HIV infection", section on 'United States'.)

IMMUNOCOMPROMISED HOSTS

ASCO guidelines for the outpatient management of neutropenia

In 2013, the American Society of Clinical Oncology (ASCO) published guidelines for antimicrobial prophylaxis of adult neutropenic oncology outpatients, for selection of patients with neutropenic fever who could be treated as outpatients, and treatment recommendations for outpatient management of such patients [21]. These guidelines focus on patients who are generally considered to be at low risk for medical complications of neutropenic fever, such as patients receiving chemotherapy for solid tumors. (See "Treatment and prevention of neutropenic fever syndromes in adult cancer patients at low risk for complications".)

IMMUNIZATIONS

Combination vaccine for meningococcus and Haemophilus influenzae type b

A combination conjugate vaccine against meningococcus serogroups C and Y and Haemophilus influenzae type b (MenHibrix, HibMenCY) was approved by the US Food and Drug Administration in June 2012 for infants and children 6 weeks to 18 months of age [22,23]. In prelicensure trials, this vaccine was safe, immunogenic, and did not interfere with immune responses to routine immunizations. In January 2013, the United States Advisory Panel on Immunization Practices began recommending HibMenCY for certain infants and toddlers at increased risk for meningococcal disease, beginning at two months of age (table 1) [24,25]. It is the first meningococcal vaccine to be recommended in the United States for use in infants younger than nine months of age. (See "Meningococcal vaccines", section on 'Combination conjugate vaccine against meningococcus and Haemophilus influenzae type b' and "Meningococcal vaccines", section on 'In infants and toddlers'.)

Tdap during pregnancy

The prevalence of pertussis in the United States has been increasing, in part because pertussis immunity after vaccination or disease wanes over time. Infants younger than three months of age are at highest risk of morbidity and mortality from this infection, and many infants contract pertussis from their mothers. Vaccination of the mother can thus significantly decrease the risk of infant exposure, and placental transfer of maternal antibodies may additionally provide a degree of passive protection to the infant for two to six months. In 2013, the United States Advisory Committee on Immunization Practices (ACIP) recommended that all pregnant women receive the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during each pregnancy, optimally between 27 and 36 weeks of gestation, regardless of prior vaccination status, to increase the likelihood of optimal protection against pertussis for both the mother and her infant during the first few months of the infant’s life [26]. Previously, Tdap was recommended only for pregnant women who had not previously received the acellular pertussis vaccine during adulthood. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, pertussis (Tdap)'.)

Safety and efficacy of influenza vaccination in pregnancy

Influenza vaccination is recommended for pregnant women because both mother and fetus are at increased risk of complications related to this infection, including fetal death. In addition, maternal vaccination provides passive protection to the infant. However, concerns about vaccine safety have interfered with compliance in this patient group. The safety and efficacy of vaccination of pregnant women were confirmed in a retrospective analysis of over 100,000 pregnancies during the 2009 influenza A (H1N1) pandemic in Norway [27]. Vaccination during pregnancy substantially reduced the risk of a maternal influenza diagnosis (adjusted hazard ratio, 0.30) and was associated with a trend in reduction of fetal death. All women who are pregnant or will be pregnant during influenza season should receive the inactivated influenza vaccine, regardless of pregnancy trimester. (See "Influenza and pregnancy", section on 'Vaccination'.)

PARASITIC INFECTIONS

Three-dose intermittent preventive treatment of malaria during pregnancy

The previous recommendation for delivering Intermittent Preventive Treatment (IPTp) for malaria to pregnant women in areas of medium and high malaria transmission was a two-dose regimen. In a systematic review and meta-analysis, use of an IPTp regimen that included three or more doses, rather than a two-dose regimen, resulted in fewer low birth weight infants, less placental malaria, and less moderate to severe maternal anemia [28]. Thus, for pregnant women who reside in areas of medium and high malaria transmission, we recommend treatment with three doses of sulfadoxine pyrimethamine as Intermittent Preventive Treatment (IPTp), rather than two doses. (See "Treatment and prevention of malaria in pregnancy", section on 'Chemoprophylaxis'.)

TICK-BORNE DISEASES

Borrelia miyamotoi infection

Borrelia miyamotoi, a species in the same taxonomic group as the agents of relapsing fever, has been found in some tick vectors and rodent reservoirs for Lyme disease agents in North America, Europe, and Asia [29]. Several reports have described clinical syndromes in patients with evidence of B. miyamotoi infection. Serologic testing on archived samples from individuals in Lyme disease-endemic regions in the United States found the seroprevalence of antibodies against B. miyamotoi to be 21.0 percent in patients who presented with a virus-like illness in the late spring or summer, 3.2 percent in patients with possible Lyme disease, and 1.0 percent in healthy individuals [30]. One patient with recent B. miyamotoi seroconversion had multiple systemic symptoms including arthralgias and inguinal adenopathy but no erythema migrans and no laboratory evidence of human granulocytic anaplasmosis coinfection. B. miyamotoi was detected in the cerebrospinal fluid of a woman with follicular lymphoma in the northeastern United States who presented with progressive mental decline over four months [31].

Additional study is necessary to further characterize the clinical syndromes caused by B. miyamotoi and to determine if this species can cause relapsing fever, an illness similar to Lyme disease, and/or distinct syndromes. (See "Clinical features, diagnosis, and management of relapsing fever", section on 'Borrelia miyamotoi infection'.)

VIRAL INFECTIONS, NON-HIV

Screening for hepatitis C in the United States

In 2013, The United States Preventative Services Task Force (USPSTF) recommended one-time screening for adults at increased risk for HCV infection and those born between 1945 and 1965 in the United States, with ongoing periodic screening for those who are at continued high risk for infection [32]. This position is in line with earlier HCV screening recommendations made by the Centers for Disease Control and Prevention and represents a change from the USPSTF’s earlier stance that made no recommendation for or against screening at-risk adults and recommended against screening asymptomatic adults who were not at increased risk. In making the updated recommendation, the USPSTF noted that the high accuracy of diagnostic tests for HCV, the improved efficacy of antiviral therapy with the introduction of newer agents, and the association of sustained virological response with a substantial reduction in morbidity and mortality together provided indirect evidence for a moderate clinical benefit to screening for HCV. (See "Screening for and diagnosis of chronic hepatitis C virus infection", section on 'United States Preventive Services Task Force'.)

Outbreak of Middle East respiratory syndrome coronavirus

In September 2012, severe pneumonia caused by a novel coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), was reported in a patient in Saudi Arabia; the patient had been ill in June 2012 [33]. Since then, additional human infections with MERS-CoV have been reported to the World Health Organization, occurring in several countries in the Arabian Peninsula, including Saudi Arabia, Qatar, Jordan, and the United Arab Emirates; the majority of cases have occurred in Saudi Arabia [34-36]. Cases have also been reported in Tunisia, Germany, the United Kingdom, France, and Italy. In all four European countries and Tunisia, a patient developed illness after returning from the Middle East. In the United Kingdom, France, Italy, and Tunisia, limited human-to-human transmission occurred among close contacts of the index cases. Most of the reported patients were severely ill and some have died. Case clusters occurring in the spring of 2013 in Saudi Arabia and France have been described in detail [37-39]. (See "Middle East respiratory syndrome coronavirus", section on 'Geographic distribution'.)

Lack of benefit of double dose oseltamivir for severe influenza

It has been proposed that giving a double dose of oseltamivir (150 mg orally twice daily) to patients with severe influenza might hasten clearance of the virus and improve outcomes. A randomized trial compared double dose and standard dose oseltamivir in 326 children and adults hospitalized in Asia with severe seasonal influenza or pandemic H1N1 influenza [40]. There was no difference between the groups in clearance of virus at day five of treatment, or in mortality or duration of supplemental oxygen, intensive care, or mechanical ventilation. (See "Treatment of seasonal influenza in adults", section on 'Dosing'.)

Avian influenza A H7N9

Beginning in late March 2013, human cases (including fatal cases) of novel avian influenza A H7N9 infection were reported in China [41-48]. Patients have presented with respiratory tract infections, many of which have progressed to severe pneumonia. Many of the affected patients had exposures to poultry before becoming ill [49,50]. To date, there is no evidence of sustained human-to-human transmission [51]. The number of new cases peaked in April and has since decreased [52], possibly as a result of control strategies including closure of live bird markets and increased public awareness. (See "Avian influenza A H7N9: Epidemiology, clinical manifestations, and diagnosis".)

Herpes zoster and tumor necrosis factor-alpha inhibitors

There have been conflicting data regarding whether tumor necrosis factor (TNF)-alpha inhibitors confer a greater risk of herpes zoster compared with other therapies in patients with underlying autoimmune disease. The largest study to address this issue was a multicenter cohort study, which compared the incidence of herpes zoster in patients with rheumatoid arthritis or another autoimmune disease who initiated a TNF-alpha inhibitor or a nonbiologic disease-modifying antirheumatic drug (DMARD) [53]. Risk for herpes zoster was not increased in patients who initiated a TNF-alpha inhibitor compared with patients initiating nonbiologic DMARDs. The study also showed that baseline use of glucocorticoids at a dose of ≥10 mg/kg per day prednisone equivalents was associated with an increased risk of herpes zoster, as seen in previous studies. (See "Tumor necrosis factor-alpha inhibitors: Risk of bacterial, viral, and fungal infections", section on 'Herpes zoster' and "Epidemiology and pathogenesis of varicella-zoster virus infection: Herpes zoster", section on 'Autoimmune disease'.)

Narcolepsy following adjuvanted 2009 pandemic H1N1 influenza vaccination

Individuals in several countries in Europe have developed narcolepsy after receiving Pandemrix, an AS03 (oil-in-water emulsion)-adjuvanted 2009 pandemic H1N1 influenza vaccine. Pandemrix was used in certain countries during the 2009-2010 H1N1 influenza pandemic, but it was not used in the United States. This association was first reported among children and adolescents in Finland and Sweden in 2010 [54]. These findings have been confirmed in a subsequent large retrospective database review that included six countries in Europe over a 10-year period; increased narcolepsy rates were observed in Sweden, Finland, and Denmark after the initiation of Pandemrix vaccination campaigns, primarily in children and adolescents [55]. An increased risk of narcolepsy was also observed in children and adolescents who received Pandemrix in the United Kingdom [56]. (See "Treatment and prevention of pandemic H1N1 influenza ('swine influenza')", section on 'Narcolepsy'.)

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