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June/July 2013
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IDSA Journal Club
June-July 2013

In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.

Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases.

Reducing Infections in the ICU: Study Supports Universal Decolonization
Reviewed by Kathryn E. Stephenson, MD, MPH

Critically ill patients are vulnerable to infections caused by colonizing bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of ventilator-associated pneumonia, surgical-site infection, and catheter-associated bloodstream infections. Decolonization using intranasal mupirocin and chlorhexidine bathing has been used to reduce transmission and prevent disease in S. aureus carriers. However, it is unclear how decolonization strategies should be applied in intensive care units (ICUs).

In the June 13 issue of the New England Journal of Medicine, investigators describe the results of a cluster-randomized, comparative-effectiveness trial in 74 adult ICUs comparing three decolonization strategies: (1) screening for MRSA on ICU admission followed by contact precautions, (2) MRSA screening and contact precautions, followed by decolonization, or (3) universal decolonization with no screening for MRSA on admission. Outcomes included ICU-attributable, MRSA-positive clinical cultures and bloodstream infections caused by MRSA or any pathogen.

In an intention-to-treat analysis, universal decolonization led to significantly reduced MRSA-positive clinical cultures compared to screening and isolation (0.63 vs. 0.92 HR; P=0.003). Universal decolonization also led to significantly reduced bloodstream infections from any pathogen compared to screening and isolation (0.56 vs. 0.99 HR; P=<0.001). Outcomes for targeted decolonization fell between those of usual care (i.e., screening and isolation) and universal decolonization.

There are limitations to the study: It is unknown if mupirocin alone has any benefit, or if decolonization could engender resistance among pathogens. The primary strength of the study is that the results are widely generalizable as the study was conducted in a broad array of hospitals, including community hospitals, and as part of routine care without the need for on-site personnel. Moreover, at the low cost of $40 per patient, this study provides support for the use of comparative-effectiveness trials for the identification of best practices.

(Huang et al. N Engl J Med. 2013;368:2255-65.)

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Update on the Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
Reviewed by Jonathan Li, MD

The first case of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), formerly known as the novel coronavirus, was reported in September 2012. The June 14 issue of the Morbidity and Mortality Weekly Report (MMWR) provided an update on the global spread of the infection, while a June 19 report in the New England Journal of Medicine described one cluster of health care-acquired MERS-CoV infections in Saudi Arabia.

In the report of the MERS-CoV hospital outbreak in Saudi Arabia, 23 cases were reported between April 1 and May 23, 2013. The most common symptoms were fever (87 percent), cough (87 percent), shortness of breath (48 percent), and gastrointestinal symptoms (35 percent). The vast majority of cases (91 percent) appeared to have been acquired through person-to-person transmission in the hemodialysis or in-patient units of three health care facilities. Those confirmed and probable MERS-CoV included five family members (out of 217 evaluated household contacts) and two health care works (out of 200 health care worker contacts). Sixty-five percent of cases (15 patients) had died at the time of publication.

The MMWR update reviewed all 55 laboratory-confirmed cases reported to the World Health Organization as of June 7. All had been linked directly or indirectly to Saudi Arabia, Qatar, Jordan, or the United Arab Emirates. Several European countries (including the United Kingdom, Italy, and France) and Tunisia have reported illnesses in returning travelers or their contacts, but no cases have yet been reported in the United States. All of the cases have presented with respiratory illness, with the majority suffering from severe disease. Overall, 31 of 55 cases had died, representing a 56 percent mortality rate.

The incubation period was initially estimated to be 1-9 days, but secondary cases have had incubation times of as long as 9-12 days. Many of the cases were reported in patients with underlying medical conditions or immunosuppression. Importantly, nasopharyngeal sampling may be of insufficient sensitivity to detect the virus and lower respiratory specimens should be collected in suspected cases (as indicated by pneumonia or suspected pneumonia and recent travel to the Arabian Peninsula or neighboring countries within 14 days of symptoms or close contact of someone who fits that description). Testing by a PCR-based assay on respiratory, blood, or stool samples is recommended.

(For the latest updates and clinical guidance, visit CDC’s website, including a July 12 MMWR update and CDC-developed preparedness checklists for health care providers and health facilities regarding MERS-CoV.)

The high mortality rate reported may be an over-estimation given recent cases with mild respiratory illness, which are far less likely to be diagnosed. Regardless, this virus has generated significant international concern as the coronavirus family of viruses can be highly transmissible in humans. While no cases have been identified yet in the United States, clinicians should ask about recent travel to the Arabian Peninsula (or exposure to a close contact with such a travel history) during the evaluation of patients with unexplained pneumonia or suspected pneumonia.

(MMWR. June 14, 2013 / 62(23);480-483 and Assiri et al. N Engl J Med. (2013) DOI: 10.1056/NEJMoa1306742.)

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Targeting CA-MRSA and Outcomes in Outpatients with Uncomplicated Cellulitis 
Reviewed by Sheila Mitsuma, MD

Current IDSA practice guidelines recommend targeting streptococci, not community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), for the treatment of non-purulent cellulitis. Limited evidence is available to support this recommendation, and antibiotics targeting community-acquired CA-MRSA are frequently used in clinical practice. In the June 15, 2013 issue of Clinical Infectious Diseases, investigators report results of a randomized-double blind, multi-center, placebo-controlled trial evaluating whether the addition of trimethoprim-sulfamethoxazole to cephalexin improves clinical outcomes in patients with uncomplicated cellulitis.

The study included 153 generally healthy adults and children presenting to emergency departments in an area endemic for CA-MRSA who were clinically diagnosed with uncomplicated cellulitis with symptoms for < 1 week.  Thirteen percent of patients had associated purulence, though those with pustules >3 mm in diameter or those with >1 cc of pus were excluded. Additional exclusion criteria included diabetes, pregnancy, any immunodeficiency, renal insufficiency and requirement for hospital admission.  Patients were randomized to receive cephalexin plus trimethoprim-sulfamethoxazole or cephalexin plus placebo. Antibiotics were prescribed until three days after patient-determined cure (minimum seven days and maximum 14 days). 

Cure was assessed at day 12 ±2 by an emergency department physician. The cure rate was 85 percent in the trimethoprim-sulfamethoxazole group and 82 percent in the placebo group (not significant) with a risk difference of 2.7 (95 percent CI, -9.3 percent to 15 percent). Neither purulent cellulitis nor nasal MRSA colonization predicted response to therapy. The intervention:placebo cure rate was 75 percent:91 percent in those initially presenting with purulence. Progression to abscess did not differ between groups, with 6.8 percent of patients developing abscesses in each group.

The above findings support IDSA’s current guidelines, which recommend against targeting CA-MRSA for non-purulent cellulitis. As the authors note, this study was modest in size and limited to generally healthy outpatients. Further study is needed to evaluate whether these findings are reproducible and can be extrapolated to other patient populations.

(Pallin et al. Clin Infect Dis. 2013;56(12):1754-1762.)

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Emergence of a Novel Avian-Origin Influenza A Virus (H7N9)
Reviewed by George R. Thompson III, MD

Genetic reassortment of influenza viruses has been well described and forms the basis for ongoing efforts to identify novel viruses as a cause of human infection. A recent report in the May 16 issue of the New England Journal of Medicine described three patients with infection due to a novel influenza A (H7N9) virus. 

Two of the three patients resided within the same city (Shanghai, China). Genetic sequencing of the H7N9 virus determined these viruses are of avian—origin only, and phylogenetic analysis revealed two of the viruses were distinct—suggesting introduction into humans on at least two separate occasions. 

Prior human infections with H7 influenza strains have generally been mild although N9 infections have not previously been found in people. All three patients in this report died from their infection despite the use of oseltamivir in all three and combined therapy with amantadine in one. All three developed the acute respiratory distress syndrome (ARDS) and were administered broad-spectrum antibiotics, glucocorticoids, and IVIG. Death occurred 6-14 days after symptom onset.  

Two patients had direct contact with poultry and there is no evidence to date of human-to-human transmission. Prior H7 outbreaks have had limited human-to-human transmission, and the pandemic potential of H7 viruses should not be underestimated.  There is currently no vaccine for H7 strains available, although candidate strains have been selected. For the latest clinical updates on H7N9, including guidance on treatment, case definitions, diagnosis and lab testing, and infection control, visit the Centers for Disease Control and Prevention website

(Gao et al. New Engl J Med. 368(20):1888-1897.)

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For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases:

July 15

  • Severe Falciparum Malaria: Effective Modern Therapy
  • Bedaquiline for Multidrug-Resistant Tuberculosis

July 1

  • The Kwashiorkor Fecal Phenotype: A Failure of Maturation
  • The Yin and Yang of Platelets in Malaria

June 15

  • Narcolepsy and Adjuvanted Influenza Vaccination
  • Interferon-ε and Protection From Sexually Transmitted Infections

June 1

  • Boosting Voriconazole
  • From “Poopsicles” to “RePOOPulation”—What's Next?
  • Human herpesvirus (HHV) 6 and HHV-7 and Febrile Status Epilepticus

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