Journal Club

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.

• Hold the Door! Association of Operating Room Door Openings with Cardiac Surgical Site Infections
• Understanding the Cryptococcal Meningitis Immune Response May Enhance Diagnosis and Treatment
• Bacteremia in Liver Transplant Patients: Leave the Immunosuppressants Alone

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, FIDSA, in each issue of Clinical Infectious Diseases.

Hold the Door! Association of Operating Room Door Openings with Cardiac Surgical Site Infections

Reviewed by Christopher J. Graber, MD, MPH, FIDSA

Surgical site infections (SSIs), particularly those associated with cardiac surgery, are associated with a high degree of morbidity and cost, so any measure that can reduce their incidence should be explored. 

A recently published article in Clinical Infectious Diseases examines the potential role that frequent operating room door openings may have in promoting SSIs. This prospective, observational study followed 688 cardiac surgeries from June 2016 through August 2017 in a cardiac surgery operating room suite in a university hospital in Switzerland. This suite consists of two operating rooms and a shared clean instrument preparation room, all equipped with laminar airflow. There is one internal door from each operating room to the instrument preparation room, two external doors from one operating room to the outside perimeter corridor, and one external door from the other operating room to the outside perimeter corridor. SSI data were collected prospectively as part of a national surveillance program.

A total of 87,676 door openings were observed for the 688 surgeries (127 per surgery; 32.4 per hour), and 24 SSIs (11 superficial, 12 deep, one frank mediastinitis) were observed. After adjustment for patient factors, increased frequency of any door opening was associated with SSI (hazard ratio [HR] 1.49 per five door openings; 95 percent confidence interval [CI] 1.11-2.00, P = 0.008) and was significant for internal (HR 2.14, 95 percent CI 1.29-3.55, P = 0.003) but not external (HR 1.32, 95 percent CI 0.82-2.11, P = 0.25) door openings.

The potential causal pathway here remains unclear (interruption of laminar airflow, marker of organization/discipline/distraction of surgical team, incomplete adjustment for complexity of surgery), and multicenter studies are needed to further explore the relationship between door openings and SSI. However, efforts to “hold the door” and limit unnecessary operating room door openings, particularly for surgeries with high risks for infection, may be low-cost but potentially beneficial interventions.

(Roth et al. Clin Infect Dis. Published online: October 13, 2018. )

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Understanding the Cryptococcal Meningitis Immune Response May Enhance Diagnosis and Treatment

Reviewed by Brian R. Wood, MD

Textbooks generally say that risk for HIV-associated cryptococcal meningitis (CM) occurs with a CD4 T cell count below 50 to 100 cells/mm³. However, immune-mediated risk and response to CM is much more complicated and depends on regulation of the Th1 versus Th2 T cell response and inflammatory cytokine profile, which affects prognosis. Better understanding of the immune-based inflammatory response to CM may enhance diagnosis as well as treatment. A recent analysis in The Journal of Infectious Diseasesadds significantly to this understanding.

Investigators analyzed data from individuals with a first episode of HIV-associated CM who were enrolled in two prospective cohort trials (COAT and ASTRO-CM) in sub-Saharan Africa.  A total of 736 participants enrolled from 2010 to 2017. Investigators compared 18-week mortality, along with other outcomes, based on CD4 count at enrollment (< 50, 50 - 99, or > 100 cells/mm³), cerebrospinal fluid (CSF) immune biomarkers, and other clinical characteristics (the CSF biomarker analysis included 345 participants who had these measured at baseline). There was no difference in antiretroviral therapy use between groups.

Several findings are notable. First, 9 percent of individuals (nearly 1 in 10) with first episode CM presented with a baseline CD4 count above 100 cells/mm³. Second, a higher proportion of individuals with a CD4 count above 100 cells/mm³ presented with altered mental status (AMS) based on a Glasgow Coma Scale score below 15 (52 percent versus 39 percent; P = 0.03).  This group, with CD4 above 100 cells/mm³, also had a 10-fold lower baseline CSF fungal burden based on quantitative cultures, higher frequency of sterile CSF culture at presentation, and higher median CSF levels of several inflammatory biomarkers. Despite these findings, this group with a relatively high baseline CD4 count did not have the best survival. The lowest mortality actually occurred in the CD4 count 50 to 99 cells/mm³ group (18-week mortality was 47 percent for the CD4 < 50 group, 35 percent for the CD4 50 - 99 group, and 40 percent for the CD4 > 100 group, which was statistically different). 

The authors describe a “damage-response” theory and postulate that individuals with CM and a CD4 count below 50 cells/mm³ have high mortality due to elevated fungal burden and lack of immune response, whereas those with a CD4 count above 100 cells/mm³ suffer more from AMS and other sequelae due to the heightened inflammatory response, which can cause neuronal damage. As the authors note, the findings raise important questions about CM treatment. While recent publications, including a new analysis in Clinical Infectious Diseases, have demonstrated that dexamethasone doesn’t improve mortality for all comers with CM due to decreases in cytokine production and fungal clearance, perhaps some individuals would benefit from this or from other adjunctive treatments that target inflammatory cytokine production. These questions are ripe for study and hopefully, in the future, data will guide individualization of CM therapy.

(Tugume et al. J Infect Dis. Published online: October 16, 2018.)

(Beardsley et al. Clin Infect Dis. Published online: August 30, 2018.)

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Bacteremia in Liver Transplant Patients: Leave the Immunosuppressants Alone

Reviewed by Erica Kaufman West, MD

Blood stream infection (BSI) in solid organ transplant recipients is common, occurring in 8-26 percent of patients, with mortality rates after transplant varying from 2-50 percent. Data to guide immunosuppressive therapy in liver transplant recipients with BSI, however, are limited. The authors of a recent article in Transplant Infectious Disease performed a retrospective single-center observational cohort study of all adult liver transplant recipients diagnosed with BSI between 2006 and 2016 at their hospital in Bologna, Italy. 

Standard immunosuppression and prophylaxis were done with usual care for rejection and cytomegalovirus infection. There were 209 episodes of BSI in 157 patients. The top three organisms found in BSI were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas. They looked at management of immunosuppressive therapy and noted if there was complete withdrawal of all immunosuppressive drugs, discontinuation of at least one drug, dose reduction of at least 50 percent in at least one drug, or any reduction in dosage of at least one drug. Ninety patients (43 percent) had some reduction/discontinuation, with 31 patients having only dose reduction and 28 with discontinuation of at least one drug. Thirteen patients had both dose reduction and discontinuation of different drugs, and complete withdrawal occurred in 18 cases. All cause 28-day mortality was 13.4 percent, varying from 7 percent in those without any reduction to 22 percent in those with any reduction. Biopsy-proven rejection was not significantly different between the groups. In analyzing risk factors for 28-day mortality, both septic shock and any reduction in immunosuppression were independently associated with increased risk of mortality.

The authors note that other studies have shown that nontransplant patient have worse mortality outcomes than transplant recipients in BSI, leading some to speculate that immunosuppression regimens may dampen the inflammatory cascade, causing less damage in sepsis. Interestingly, other studies have shown that anti-inflammatory drugs do not improve outcomes in severe sepsis or septic shock. Whatever the mechanism, this study suggests that liver transplant patients with BSI will do better if we focus on treating the infection and avoid the temptation to cut their immunosuppression medications.

(Bartoletti et al. Transplant Infect Dis. 2018;20:e12930.)

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