General ID: July 2018

Which is better for murine typhus: doxycycline or azithromycin? This open-label RTC in performed in Laos compared 7 days of doxycycline, 3 days of doxycycline, or 3 days of azithromycin for murine typhus. The outcomes of interest were time to resolution of fever and rates of treatment failure or relapse. Seventy-two patients per arm were enrolled, of whom 73% had a serologically or PCR-confirmed diagnosis. Rates of treatment failure were significantly higher in the azithromycin arm (23%) versus the 3-day doxycycline arm (4%) or the 7-day doxycycline arm (1%). Fever clearance occurred more rapidly in the patients given doxycycline than azithromycin, and no relapses occurred in any arm.

Murine typhus is rampant here in south-central Texas; I probably saw half a dozen cases in the first year of fellowship. In at least two cases, the diagnosis was not initially considered because the patient had no pets or direct animal contacts, but we later learned that the patients left food out for stray cats in the neighborhood (meals inevitably shared by the local raccoons and possums), suggesting the patinets were bitten by fleas deposited near the food bowl. No good deed goes unpunished! 30020447

Say you’ve just diagnosed falciparum malaria. Should you withhold empiric antibiotics? If you do, you may be leaving concomitant bacteremia untreated. This case series examined admission blood cultures from twenty consecutive patients hospitalized in Myanmar for P. falciparum malaria. Four patients (20%) had a clinically significant bacteremia. The authors pooled their data with a previous multicenter study of bacteremia in patients hospitalized for P. falciparum (total n=87), among whom 15% had a clinically significant bacteremia. A quarter of the cases were due to S. aureus and the remainder due to gram-negative bacilli. Bacteremia occurred more frequently in severe cases of malaria, was often not suspected clinically, and was associated with greater mortality (15% vs 1%). 30014826

What do imaging and blood cultures add to the diagnosis of cellulitis? Cost, mostly. This was a retrospective cohort study of 183 patients presenting to a single ED with presumed cellulitis who were admitted to either the medicine wards or ED observation. The authors assessed the diagnostic yield and costs of laboratory and radiographic tests performed to evaluate the patients’ cellulitis diagnoses. They found that 33% of patients received a blood culture, which by IDSA guidelines were only indicated in 10% of patients; of these, only one (1.7%) was positive. Sixty-eight percent of patients received imaging, most of which consisted of ultrasounds and plain films and none of which was concordant with IDSA guidelines. Imaging studies changed management in 6.5% of cases, by diagnosing abscess in five cases, osteomyelitis in two cases, and hematoma in one case. When diagnosis and management were affected, it was usually due to the results of an MRI or CT rather than plain films or ultrasound. The authors conclude that guidelines-discordant blood cultures and imaging in cellulitis are seldom helpful and estimate the costs of these tests in the US to be about 227 million dollars annually. 29610842

Do you think of Hepatitis E virus as a chronic infection? I hadn’t, but this study of Chinese blood donors revealed that people can be infected with HEV for months without clinical symptoms or seroconversion. The authors screened blood donations for HEV using IgM, IgG, viral antigen, and RT-PCR testing. They identified 24 of 11747 donors (0.2%) who had HEV viremia and antigenemia without any apparent illness or clinical hepatitis. Of these, 17 donors provided follow-up blood samples; 10 had viremia or antigenemia for more than 70 days, and 3 had such for more than 90 days. Interestingly, 14 of the 17 subjects did not have any serologic response during the study period. This study raises the question – is serologic screening adequate to protect the blood supply from transmission of HEV? Perhaps pooled blood samples should be screened with antigen and RT-PCR testing? 29977038

“Bacterial ghosts” are both a novel vaccine delivery system and a novel form of vaccine adjuvant. This manuscript was the first I’d heard of bacterial ghost technology, which is why I thought it was worth sharing. Bacterial ghosts are empty bacterial cell envelopes with preserved membrane antigens. To use them as a vaccine, the authors first took several N. gonorrhea antigens that produce potentially protective immune responses in animal models and expressed them as recombinant proteins in E. coli. Then, they transfected S. enteritidis with a plasmid carrying a lysis gene controlled by a heat-sensitive regulatory element, grew up large quantity of these bacteria, then heated the culture to induce cell lysis. They produced the bacterial ghosts by washing and centrifuging the S. enteriditis lysate, then loading the ghosts isolated from the lysate with recombinant N. gonorrhea protein. They found that immunizing mice with the recombinant protein-loaded bacterial ghosts produced higher antibody levels and more robust lymphoproliferative responses that immunizing the mice with the N. gonorrhea proteins alone. Perhaps this technology will finally allow development of an effective gonorrhea vaccine. 29914847

If you are still treating community-acquired pneumonias with more than five days of antibiotics, read this and then stop. This meta-analysis of 21 clinical trials (19 RTCs; total n=4861) compared clinical cure and adverse events associated with giving <6 versus >7 days of antibiotics for CAP. Rates of clinical cure were identical between the short versus long durations of therapy, which was true regardless of clinical setting or pneumonia severity; in addition, there was no difference in rates of relapsed infection. However, short-duration antimicrobial therapy was associated with fever adverse events (RR 0.73) and lower mortality (RR 0.52) than longer antibiotic courses.

Granted, the majority of the studies included showed nonsignificant trends favoring improved outcomes in the short-course study arms, which only become statistically significant with pooling of the data. Nonetheless, we can certainly say that short course antibiotic therapy for CAP (5 days or less) is at least as efficacious as >7 days of therapy and may be superior, and it is clearly better tolerated. It’s worth pointing out that although only 8 studies included patients with HIV or other immunocompromise, a majority of the studies included patients with other significant comorbidities, including renal and liver insufficiencies and COPD. So, resist the urge to label your patient as “too sick” for a five-day treatment course based on their end-organ diseases. 29987137