The utility of proadrenomedullin and procalcitonin in comparison to C-reactive protein as predictors of sepsis and bloodstream infections in critically ill patients with cancer*.

OBJECTIVES: Infections in critically ill patients continue to impose diagnostic and therapeutic challenges. We seek to investigate the utility of proadrenomedullin and procalcitonin as diagnostic and prognostic biomarkers in febrile critically ill patients with cancer and compare their performance with that of C-reactive protein. DESIGN: Single-center prospective cohort study. SETTING: Tertiary care, academic, university hospital. PATIENTS: One hundred fourteen critically ill patients with cancer with fever. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples were withdrawn on the day of fever onset and 4 to 7 days thereafter, and the serum proadrenomedullin, procalcitonin, and C-reactive protein levels were measured using the Kryptor technology afterward. Of the 114 adult patients, 27 had bloodstream infections, 36 had localized infections, and the remaining had no infections. The area under the receiver operating characteristic curve for bloodstream infection diagnosis was significantly greater for proadrenomedullin (0.70; 95% CI, 0.59-0.82) and procalcitonin (0.71; 95% CI, 0.60-0.83) compared with C-reactive protein (0.53; 95% CI, 0.39-0.66) (p = 0.021 and p = 0.003, respectively). Receiver operating characteristic analysis also showed that proadrenomedullin (p = 0.005) and procalcitonin (p = 0.009) each had a better performance than C-reactive protein in predicting patients' mortality within 2 months after their fever onset. Regarding patients' response to antimicrobial therapy, proadrenomedullin, procalcitonin, and C-reactive protein levels all significantly decreased from baseline to follow-up in responders (p ≤ 0.002), whereas only proadrenomedullin level significantly increased in nonresponders (p < 0.0001). In patients with documented infections, proadrenomedullin (0.81; 95% CI, 0.71-0.92) and procalcitonin (0.73; 95% CI, 0.60-0.85) each had a greater area under the curve compared with C-reactive protein (0.59; 95% CI, 0.45-0.73) as for as predicting response (p = 0.004 and p = 0.043, respectively). However, for all febrile patients, proadrenomedullin had a significantly greater area under the curve for predicting favorable response than procalcitonin (p < 0.0001). CONCLUSION: In critically ill patients with cancer, proadrenomedullin and procalcitonin both have a promising role in predicting bloodstream infections in a manner more helpful than C-reactive protein. These two biomarkers were superior to C-reactive protein in the prognostic analysis of response to antimicrobial therapy for those patients with documented infections. However, proadrenomedullin was superior to procalcitonin in predicting response in all febrile patients and was unique in showing increased levels among nonresponders.

Central line-associated bloodstream infections caused by Staphylococcus aureus in cancer patients: Clinical outcome and management.

BACKGROUND: There are limited data regarding clinical presentation and management of Staphylococcus aureus central line- associated bloodstream infection (CLABSI) in immunocompromised cancer patients. METHODS: In this review, we evaluated 299 patients with 304 episodes of S. aureus-CLABSI between 2005 and 2011. FINDINGS: By multivariate analysis, the major predictors of complicated S. aureus-CLABSI were septic shock, catheter site inflammation, presence of peripherally inserted central catheter, anti-cancer chemotherapy within 10 days, and persistent bacteremia beyond 72 hours (P ≤ 0.02). A total of 67% of the cases were defined as complicated. In the subset of patients who were uncomplicated on presentation, patients receiving antimicrobials ≥ 14 days had similar rates of relapse, attributable mortality, and development of complications compared to those receiving shorter-course therapy. By competing risk analysis, removal of the catheter within 3 days of the onset of bacteremia was associated with a lower relapse rate at 90 days (P = 0.024). INTERPRETATION: The majority of S. aureus-CLABSI in cancer patients are complicated and require prolonged course of antimicrobial treatment. Early removal of the catheter within the first 3 days is associated with better course. In patients with prompt removal of the catheter and no evidence of a complicated course, treatment beyond 2 weeks may not be necessary.

Can procalcitonin differentiate Staphylococcus aureus from coagulase-negative staphylococci in clustered gram-positive bacteremia?

Procalcitonin (PCT) and pro-adrenomedullin (ProADM) have been proposed as diagnostic and prognostic biomarkers of infection. Between July 2009 and January 2012, we studied the role of these biomarkers in 163 patients with clustered gram-positive and gram-negative bacteremia. PCT levels were significantly higher in patients with Staphylococcus aureus and gram-negative bacteremia than those with coagulase-negative staphylococci (CoNS) isolated from blood cultures (P = 0.29 and <0.001, respectively). ProADM levels were only significantly higher in patients with gram-negative bacteremia (median 1.46 nmol/L) than those with CoNS (median 1.01 nmol/L) (P = 0.04). Among patients with CoNS, PCT, and ProADM, levels failed to differentiate blood contamination (medians 0.24 ng/mL and 0.97 nmol/L) from true bacteremia (medians 0.26 ng/mL and 1.14 nmol/L) (P = 0.51 and 0.57, respectively). In cancer patients, PCT (and to a lesser extent, ProADM) was useful in differentiating CoNS from S. aureus and gram-negative bacteremia.

Pro-adrenomedullin as a novel biomarker for predicting infections and response to antimicrobials in febrile patients with hematologic malignancies.

BACKGROUND: Health professionals and researchers have become increasingly interested in biomarkers that help them in diagnosis of infections with recent growing attention to procalcitonin (PCT) and pro-adrenomedullin (proADM). METHODS: This study compares proADM to PCT as diagnostic and prognostic biomarkers of infection in febrile patients with hematologic malignancies (HMs). From June 2009 to December 2010, 340 febrile HM patients were evaluated for presence of sepsis, systemic inflammatory response syndrome (SIRS), documented infections, and response to antimicrobial therapy. RESULTS: ProADM and PCT levels were measured at onset of fever and then on days 4-7 afterward. Of the 340 patients, 103 had definite sepsis, and 159 had SIRS. Only proADM initial levels were significantly higher in patients with localized bacterial infections than in those with no documented infection (P = .019) and in patients with definite sepsis than those with SIRS (P = .023). The initial proADM and PCT levels were significantly higher in neutropenic patients with BSIs than in those without documented infections (P = .010 and P = . 011, respectively). Follow-up, proADM, and PCT levels decreased significantly in response to antimicrobial therapy in patients with bacterial infections (BSIs or localized; P = .007 and P = .002, respectively). CONCLUSIONS: ProADM and PCT have promising roles in assisting clinicians in managing febrile HM patients. However, proADM appears to have the advantage of predicting localized bacterial infection and differentiating sepsis from SIRS.

Nephrostomy tube related pyelonephritis in patients with cancer: epidemiology, infection rate and risk factors.

PURPOSE: Nephrostomy tube placement is often necessary to avert acute renal failure in patients with cancer with obstructive uropathy or in patients with ureteral leak. However, there have been limited published studies on the rate and risk of nephrostomy tube related pyelonephritis in patients with cancer. Therefore, in this study we determined rates of nephrostomy tube related pyelonephritis and predisposing risk factors in patients with cancer. MATERIALS AND METHODS: We retrospectively reviewed patients who underwent nephrostomy tube placement between September 1, 2009 and September 16, 2010 at MD Anderson Cancer Center. Patients were followed for 90 days. The primary outcome assessed was the development of nephrostomy tube related pyelonephritis and the secondary outcome was the development of asymptomatic bacteriuria. We also determined risk factors associated with pyelonephritis. RESULTS: Of the 200 patients analyzed 38 (19%) had pyelonephritis and 15 (7.5%) had asymptomatic bacteriuria. Of the nephrostomy tube related infections 34 cases (89%) were with the primary nephrostomy tube. Subsequently 4 of the patients who underwent nephrostomy tube exchange had an episode of pyelonephritis. Pyelonephritis developed within the first month in 19 (10%) patients. Prior urinary tract infection and neutropenia were found to be significant risk factors for pyelonephritis (p = 0.047 and 0.03, respectively). CONCLUSIONS: The placement of nephrostomy tubes in patients with cancer is associated with a significant rate of pyelonephritis. Neutropenia and history of urinary tract infection were significant risk factors for pyelonephritis. This finding warrants further investigation into preventive strategies to reduce the infection rate.

Can procalcitonin distinguish infectious fever from tumor-related fever in non-neutropenic cancer patients?

BACKGROUND: Procalcitonin (PCT) has been proposed as a marker of infection and was studied in neutropenic patients. This study investigated its role in non-neutropenic febrile cancer patients (NNCPs). METHODS: Between July 2009 and July 2010, a total of 248 NNCPs with fever were studied. PCT was measured in plasma within 24 hours of fever onset and 4 to 7 days thereafter, using a Kryptor system with a lower limit of quantitation of 0.075 ng/mL. Patients' clinical, microbiological, and radiological data were reviewed to make the diagnosis and were correlated with PCT levels. RESULTS: This study included 30 patients with bloodstream infection (BSI), 60 with localized bacterial infection, 141 with no documented infection, and 8 with tumor-related fever. Most patients (98%) were inpatients or admitted to the hospital during the study. Patients with BSI had significantly higher PCT levels than did those with documented localized infections (P = .048) and no documented infection (P = .011). PCT levels were significantly higher in septic patients than in those without sepsis (P = .012). Patients with stage IV disease or metastasis had significantly higher baseline PCT levels than did those with early stages of cancer (P < .05). PCT levels dropped significantly in patients with bacterial infections in response to antibiotics (P < .0001). CONCLUSIONS: Baseline PCT levels are predictive of BSI and sepsis in NNCPs. They may be predictors of metastasis and advanced cancer. Subsequent decrease in PCT levels in response to antibiotics is suggestive of bacterial infection. Larger trials are needed to confirm the results of this pilot study.