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June 2011
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IDSA Journal Club
June 2011

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.


Molecular Assays to Detect Congenital CMV Infection
Reviewed by Jason Weinberg, MD

Real-time PCR assays of saliva specimens are highly sensitive and specific for the detection of cytomegalovirus (CMV) in newborns, according to an article in the June 2 issue of The New England Journal of Medicine.

Approximately 30,000 children are born with congenital CMV infection each year, and 10 percent to 15 percent of CMV-positive children go on to develop sensorineural hearing loss. To determine whether a new real-time PCR-based assay would be an effective tool to detect congenital CMV infection, 34,989 subjects were prospectively enrolled in a study in which saliva specimens were collected from newborn infants. Results of real-time PCR testing of liquid saliva and dried saliva specimens were compared to results from a rapid culture assay for CMV.

A total of 177 (0.5 percent) infants were CMV-positive by at least one of the three methods. When compared to standard rapid culture, PCR testing of liquid saliva had a sensitivity of 100 percent and specificity of 99.9 percent, and PCR testing of dried saliva had a sensitivity of 97.4 percent and specificity of 99.9 percent. Positive and negative predictive values were greater than 90 percent for both PCR assays. There was 100 percent agreement between the two PCR assays when they were compared head-to-head in a subset of samples obtained from 5,276 patients.

Because the majority of infants with congenital CMV infection are not identified during the newborn period, a simple and reliable screening tool is needed. The results of this study suggest that real-time PCR assays of saliva, especially dried saliva, may provide such a tool that could be readily adapted to high-throughput platforms. No DNA extraction step was used for the samples in this study, further simplifying the assay. Early identification of CMV-positive newborns will facilitate the monitoring of, and early intervention for, infants at risk for hearing impairment.

(Boppana et al. New Engl J Med. 2011; 364:2111-2118.)

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Bacterial Meningitis in the United States, 1998–2007: Changes in Epidemiology
Reviewed by Ed Dominguez, MD

Haemophilus influenzae type b (Hib) conjugate vaccine, pneumococcal conjugate vaccine, and universal screening of pregnant women for group B streptococcus (GBS) have contributed to a steady decline in the incidence of bacterial meningitis in the United States. An evaluation reported in the May 26 issue of The New England Journal of Medicine sought to determine the influence of these interventions on the epidemiology of bacterial meningitis.

Between 1998 and 2007, the authors identified 3,188 cases of bacterial meningitis due to H. influenzae, S. pneumoniae, N. meningitidis, Group B streptococci, or L. monocytogenes within the Active Bacterial Core surveillance (ABCs) and the Foodborne Diseases Active Surveillance Network (FoodNet), surveillance systems in the Emerging Infections Program Network. The incidence of bacterial meningitis caused by these bacteria decreased by from 2.00 cases per 100,000 population in 1998 to 1.38 cases per 100,000 population in 2007, a decline of 31 percent. Despite this decreasing incidence, there was no significant change in the case fatality rate from bacterial meningitis (15.7 percent in 1998, 14.3 percent in 2007). A marked decline in the incidence of pediatric meningitis accounted for an increase in the overall median age of patients, from 30.3 years to 41.9 years. However, there was no change in the incidence in children under 2 months of age.

For each pathogen other than Group B streptococci (which increased slightly, by 4 percent), there was a significant decline, ranging from 26 percent for S. pneumoniae to 58 percent for N. meningitidis. S. pneumoniae caused 58 percent of meningitis cases. Importantly, the authors found the incidence of meningitis caused by strains covered in the heptavalent protein-polysaccharide pneumococcal conjugate vaccine declined precipitously, by 92 percent. However, the incidence of meningitis caused by non-vaccine strains increased by 61 percent. This lucid snapshot of bacterial meningitis provides a useful standard for future interventional and therapeutic studies.

(Thigpen et al. New Engl. J Med. 2011; 364:2016-25.)

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Effect of Corticosteroids on the Clinical Course of CAP: An Ongoing Debate
Reviewed by George R. Thompson III

Despite advances in antimicrobial therapy and critical care medicine, community acquired-pneumonia (CAP) remains the number one cause of infectious disease related mortality. Recent clinical trials have shown respiratory, hemodynamic, and immunologic benefits of corticosteroid treatment in the critically ill. The reduced inflammatory response in corticosteroid-treated patients is thought to contribute to improvements in oxygenation and subsequently morbidity and mortality although prospective data is limited.

The authors of a study published in the March 15 issue of Critical Care performed a prospective, randomized, double-blind, placebo-controlled trial comparing patients treated with methylprednisilone (200 mg bolus followed by a nine day taper) and ceftriaxone plus levofloxacin to those receiving ceftriaxone plus levofloxacin alone. Omeprazole was administered to all patients, and insulin was initiated as needed.

The primary outcome of interest, respiratory failure requiring mechanical ventilation, was less common in the corticosteroid treated group, although differences were not statistically significant. However, patients in the corticosteroid-treated group showed a more rapid decrease of fever, radiologic improvement, and improvement in PaO2/FiO2 ratios than those in the control group (P=<0.05). Side effects of treatment were not significantly different between groups, although one patient in the corticosteroid-group required insulin therapy, and one suffered gastrointestinal bleeding that was managed conservatively and without significant sequalae.

The authors’ results are intriguing, although likely underpowered to reach their primary outcome of interest. Larger studies will be needed to determine the usefulness and specific populations that may benefit from adjunctive corticosteroid therapy in the treatment of CAP. 

(Fernandez-Serrano et al. Crit. Care 2011;15(2):R96.)

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Intraventricular Antibiotics for Post-Neurosurgical Meningitis or Ventriculitis
Reviewed by Khalil Ghanem, MD, PhD

The use of intraventricular antibiotics to treat post-neurosurgical ventriculitis and meningitis is controversial. A recent study published in the June 1 issue of Clinical Infectious Diseases suggests that intraventricular gentamicin, in addition to intravenous antibiotics, enhances cure rates in Gram-negative bacillary meningitis.

This was a retrospective case series of 31 consecutive patients at a single center who were diagnosed with post-neurosurgical ventriculitis or meningitis and who were followed for three months. Thirteen patients were given combination intravenous antibiotics with intraventricular gentamicin (4–8 mg once daily), while the remainder were only treated with intravenous antibiotics. Cure was defined as resolution of clinical and laboratory signs of meningitis, negative cerebrospinal fluid (CSF) culture results (if performed), and no relapse within three months after stopping antibiotics. Treatment failure was defined as death attributable to meningitis or relapse within three months.

The bacteria isolated from the CSF were Enterobacter (55 percent), Pseudomonas (16 percent), Klebsiella (10 percent), Xanthomonas (6 percent), and Escherichia (3 percent). The main intravenous therapies used were meropenem, cefotaxime, ceftazidime, imipenem, and trimethoprim-sulfamethoxazole. Relapse occurred in none of the 13 patients treated intraventricularly and in six of 18 patients treated with systemic antibiotics alone. All patients who experienced relapse eventually recovered with prolonged intravenous antibiotic treatment or treatment with intraventricular gentamicin. Mortality at three months was similar in both groups. No toxicities due to the intraventricular use of gentamicin were reported.

Given the difficulty in treating some of these infections, this study does provide some reassurance as to the safety and possible benefits of intraventricular gentamicin use in select patients with Gram-negative ventriculitis. The study, however, was a small retrospective case series. Certain group differences may have impacted the outcome. Larger controlled trials are needed before recommendations for the routine use of intraventricular antibiotics are made.

(Tangden et al. Clin Infect Dis.  2011;52:1310-16.)

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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:

June 15

  • Mycobacterium Tuberculosis and the Host Response: A Story That Seems to Keep Getting Stranger
  • Acute HCV in HIV-Infected Patients; To Treat or Not To Treat, That Is The Question

June 1

  • Clostridium Difficile Toxins
  • Tigecycline and Hospital-Acquired Pneumonia
  • Anaplasma and Ixodes: Keeping warm with Snuggling and Antifreeze

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