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.

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.

Improved antibiotic-impregnated catheters with extended-spectrum activity against resistant bacteria and fungi.

Minocycline-rifampin-impregnated central venous catheters (M/R CVCs) have been shown to be efficacious in reducing catheter-related bloodstream infections (CRBSI) and inhibiting the biofilm adherence of resistant Gram-positive and Gram-negative pathogens, with the exception of Pseudomonas aeruginosa and Candida spp. To expand the spectrum of antimicrobial activity, a novel second-generation M/R catheter was developed by adding chlorhexidine (CHX-M/R). CVCs and peripherally inserted central catheters (PICCs) were impregnated with CHX-M/R and compared with first-generation M/R catheters, CHX-silver sulfadiazine-treated CVCs (CHX/SS-CVCs), chlorhexidine-treated PICCs, and uncoated catheters. A biofilm catheter colonization model was used to assess the efficacy of catheters against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), P. aeruginosa, Candida albicans, and Candida glabrata. CHX-M/R-impregnated CVCs were the only antimicrobial catheters that completely inhibited the biofilm colonization of all resistant bacterial and fungal organisms tested at all time intervals, and they were significantly superior to uncoated catheters (all P values were ≤0.003). Furthermore, CHX-M/R-coated CVCs had a significantly more effective and prolonged (up to 3 weeks) antimicrobial activity against MRSA and P. aeruginosa than M/R, CHX/SS, and uncoated CVCs (P < 0.0001). Similarly, CHX-M/R-coated PICCs were also superior to M/R-coated and CHX-coated PICCs in preventing biofilms of MRSA, VRE, P. aeruginosa, and Candida species (P value = 0.003 for all). Our study shows that novel CHX-M/R-coated catheters have unique properties in completely inhibiting biofilm colonization of MRSA, VRE, P. aeruginosa, and fungi in a manner superior to that of M/R- and chlorhexidine-treated catheters.

Unnecessary Removal of Central Venous Catheters in Cancer Patients with Bloodstream Infections.

We evaluated the rate of central venous catheter (CVC) removal in 283 cancer patients with bloodstream infections (BSIs). Removal of CVCs occurred unnecessarily in 57% of patients with non-central-line-associated BSI (non-CLABSI), which was equivalent to the rate of CVC removal in patients with CLABSIs. Physician education and safe interventions to salvage the vascular access are warranted. Infect Control Hosp Epidemiol 2018;39:222-225.

Removal and insertion of central venous catheters in cancer patients is associated with high symptom burden.

OBJECTIVES: To assess the symptom burden associated with CVC removal and insertion in cancer patients. METHODS: We collected patient-reported symptom-burden outcomes for 60 consecutive cancer patients: 30 undergoing CVC removal and 30 undergoing CVC insertion. Cancer patients self-administered the MD Anderson Symptom Inventory to rate the severity of 21 different symptoms immediately after the procedure Results: Symptoms were present in up to 57% to 67% of patients undergoing CVC insertion and removal respectively. Nineteen patients (32%) were moderately symptomatic with a symptom burden of four or more: ten insertion and nine removal patients. Symptoms with a score of 4 or more clustered around physical symptoms (pain, pressure or burning) or more generalized symptoms (fatigue, sleep, distress, dry mouth, and drowsiness). Nine (15%) patients rated at least one symptom as eight or more, five (17%) being insertion patients. CONCLUSIONS: CVCs are essential for the management of cancer patients. However, they can become infected and may need to be removed. Catheter removal and insertion produced moderate to severe symptom burden in cancer patients. Safe interventions that would salvage the vascular access without worsening the infectious outcome should be explored to alleviate morbidity associated with the symptom burden of removal and re-insertion.

Procalcitonin Guiding Antimicrobial Therapy Duration in Febrile Cancer Patients with Documented Infection or Neutropenia.

In this analysis, we identified febrile cancer patients with documented infections or neutropenia, whose procalcitonin levels are low at baseline or decrease on antibiotics. These patients had similar outcomes in terms of mortality and relapse of infection regardless of the duration of antimicrobial therapy (less or more than 7 days).

Author Correction: Procalcitonin Guiding Antimicrobial Therapy Duration in Febrile Cancer Patients with Documented Infection or Neutropenia.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Improvement in the diagnosis of catheter-related bloodstream infections in a tertiary cancer center.

BACKGROUND: Identifying a central venous catheter (CVC) as the source of bacteremia requires drawing simultaneous blood cultures (BCs) from the CVC and peripheral site and correct labeling of the BC source. In our emergency center (EC), 52% of BCs collected from febrile cancer patients lacked source information, making the diagnosis and management of catheter-related bloodstream infections (CRBSIs) challenging. METHODS: Between January 2015 and June 2015, we conducted a quality improvement project in our EC aiming to increase the occurrence of simultaneous BC drawing with accurate source labeling by 10%. RESULTS: Staff education and monitoring increased average BC source labeling from a baseline of 48% to a much better rate of 70%. Label introduction led to increased source labeling to 94% by June 2015. This project had a significant influence in patients with a CVC and a positive BC because the physician is now able to determine whether the CVC is the source of the bacteremia in 88% of cases compared with 36% at baseline (P = .0003). CONCLUSIONS: Education without an active intervention is usually not enough. Simple solutions such as label introduction can have significant influence on patient safety and care. Accurate diagnosis may guide clinicians at the bedside to appropriately manage CVCs in the setting of bacteremia, remove a CVC when indicated, and prevent unnecessary CVC removal with its potential safety and cost-effectiveness implications.

Role of Procalcitonin and Interleukin-6 in Predicting Cancer, and Its Progression Independent of Infection.

Procalcitonin (PCT) and Interleukin-6 (IL-6) have emerged as biomarkers for different inflammatory conditions. The purpose of the study was to evaluate the role of PCT and IL-6 as biomarkers of cancer and its progression in a large cohort of patients. This cross-sectional study included residual plasma samples collected from cancer patients, and control subjects without cancer. Levels of PCT and IL-6 were determined by Kryptor compact bioanalyzer. We identified 575 febrile cancer patients, 410 non-febrile cancer patients, and 79 non-cancer individuals. The median PCT level was lower in control subjects (0.029 ng/ml) compared to cancer patients with stage I-III disease (0.127 ng/ml) (p<0.0001) and stage IV disease (0.190 ng/ml) (p<0.0001). It was also higher in febrile cancer patients (0.310 ng/ml) compared to non-febrile cancer patients (0.1 ng/ml) (p<0.0001). Median IL-6 level was significantly lower in the control group (0 pg/ml) than in non-febrile cancer patients with stages I-III (7.376 pg/ml) or stage IV (9.635 pg/ml) (p<0.0001). Our results suggest a potential role for PCT and IL-6 in predicting cancer in non-febrile patients. In addition, PCT is useful in detecting progression of cancer and predicting bacteremia or sepsis in febrile cancer patients.

Identification and characterization of catheter-related bloodstream infections due to viridans group streptococci in patients with cancer.

Viridans group streptococci (VGS), a leading cause of bloodstream infection (BSI) in cancer patients, are thought to arise from the gastrointestinal tract. We sought to determine whether central venous catheters may serve as the source of VGS BSI, and to compare the ability of the newly proposed mucosal barrier injury laboratory-confirmed BSI definition to assign a VGS BSI source compared with the catheter-related BSI definition.