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 MEASUREMENTS AND MAIN RESULTS: Blood samples were withdrawn on the day of fever onset and 4 to 7 days thereafter, and the serum proadrenomedullin, procalcitonin, and C-reactive protein levels were measured using the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.

US practitioner opinions and prescribing practices regarding corticosteroid therapy for severe sepsis and septic shock.

PURPOSE: The aim of this study was to examine opinions and practices of US critical care practitioners (USCCPs) toward corticosteroid therapy in adult patients with severe sepsis or septic shock. MATERIALS AND METHODS: A multicenter, electronic survey of USCCP members of the Society of Critical Care Medicine was conducted between March 18 and July 31, 2009. RESULTS: A total of 542 USCCPs responded to the survey. The majority (83%) do not commonly use corticosteroids in adult patients with severe sepsis; however, up to 81% report use of corticosteroids for septic shock. Twenty-eight percent believe that corticosteroids reduce mortality in septic shock, whereas 27% do not and 45% are unsure. The decision to initiate therapy is based, more often, on a patient's clinical status (65%) vs serum cortisol analysis (35%). Hydrocortisone is the most common corticosteroid prescribed (93%), with a median dosage of 200 mg/d and administration via intermittent intravenous injection. The Corticosteroid Therapy of Septic Shock trial had a large impact on survey respondents, with 62% reporting a practice change. Among the 19% of practitioners who do not prescribe corticosteroids, the most common reason was lack of proven survival benefit. CONCLUSIONS: Corticosteroids are commonly used by USCCPs in adult patients with septic shock; however, criteria used to initiate therapy and opinions regarding their impact vary.

Critical illness-related corticosteroid insufficiency in cancer patients.

PURPOSE: Critically ill cancer patients with sepsis represent a high-risk sub-group for the development of critical illness-related corticosteroid insufficiency (CIRCI); however, the incidence of CIRCI in this population is unknown. The purpose of this study was to determine the incidence of CIRCI in cancer patients with severe sepsis or septic shock. METHODS: A single-center, retrospective, observational study was conducted in a 52-bed medical-surgical intensive care unit of a National Cancer Institute-recognized academic oncology institution. Eighty-six consecutive patients with a diagnosis of severe sepsis or septic shock who received a high-dose 250-µg cosyntropin stimulation test were included. CIRCI was identified by a maximum delta serum cortisol of 9 µg/dL or less post cosyntropin. RESULTS: Overall, 59% (95% CI, 48-70%) of cancer patients with severe sepsis or septic shock were determined to have CIRCI. When compared to patients without CIRCI, patients with CIRCI had higher baseline serum cortisol (median, 26.3 versus 14.7 µg/dL; p = 0.002) and lower delta cortisol levels (median, 3.1 versus 12.5 µg/dL; p < 0.001). Mortality did not differ between the two groups. An inverse relationship was identified between baseline serum cortisol and maximum delta cortisol (maximum delta cortisol = -0.27 × baseline cortisol + 14.30; R (2) = 0.208, p < 0.001). CONCLUSIONS: The incidence of CIRCI in cancer patients with severe sepsis or septic shock appears high. Further large-scale prospective trials are needed to confirm these findings.

Clinical effectiveness and risk of emerging resistance associated with prolonged use of antibiotic-impregnated catheters: more than 0.5 million catheter days and 7 years of clinical experience.

OBJECTIVES: Catheters coated with minocycline and rifampin are proven to decrease the rates of central line-associated bloodstream infection; however, it is unclear whether success occurs independent of other infection control precautions. We evaluated the effect of catheters coated with minocycline and rifampin with and without other infection control precautions on our rates of central line-associated bloodstream infection in critically ill patients and on antibiotic resistance throughout the hospital and in the intensive care unit. DESIGN: Retrospective clinical cohort study conducted during 1999-2006 with an observational laboratory component. SETTING: A tertiary university-based cancer center. PATIENTS: All 8009 patients admitted to the medical intensive care unit were subjects for the surveillance of central line-associated bloodstream infection. All Staphylococcus aureus and coagulase-negative staphylococci clinical isolates cultured at our institution during the same period were subjects for laboratory testing. INTERVENTIONS: Using catheters coated with minocycline and rifampin and implementing infection control precautions. MEASUREMENTS AND MAIN RESULTS: Incidence of central line-associated bloodstream infection in the medical intensive care unit. Change in resistance to tetracycline and rifampin in clinically relevant staphylococcal isolates in the intensive care unit and hospitalwide. During the study period, 9200 catheters coated with minocycline and rifampin were used hospitalwide over a total of 511,520 catheter days. The incidence of central line-associated bloodstream infection per 1000 patient days in the medical intensive care unit significantly and gradually decreased from 8.3 in 1998 to 1.2 in 2006 (p ≤ .001). The resistance of S. aureus and coagulase negative staphylococci clinical isolates to tetracycline or rifampin in the intensive care unit and on a hospitalwide level remained stable or decreased significantly during the same period. CONCLUSIONS: Catheters coated with minocycline and rifampin significantly decreased the incidence of central line-associated bloodstream infection in the medical intensive care unit in a manner that was independent and complementary to the infection control precautions. Although this study strongly suggests an association between catheters coated with minocycline and rifampin use and a decrease in central line-associated bloodstream infection, because of multiple other concurrent interventions, the results should be interpreted cautiously until a prospective study is conducted. Furthermore, long-term use of these devices is not associated with increased resistance of staphylococcal isolates to tetracycline and rifampin in the intensive care unit or throughout the hospital.

Novel approach using antimicrobial catheters to improve the management of central line-associated bloodstream infections in cancer patients.

BACKGROUND: Central venous catheter (CVC) removal has often been recommended for the treatment of central line-associated bloodstream infections (CLABSIs). However, CVC removal is not always practical in patients with cancer, and changing CVCs with noncoated CVCs over guidewire may result in cross-infection of the new CVC. Therefore, the current matched retrospective cohort study was conducted to evaluate the effectiveness of exchanging infected CVCs for minocycline- and rifampin (MR)-coated CVCs in cancer patients with CLABSIs. METHODS: The authors identified all cancer patients with CLABSIs who had undergone either CVC exchange with MR-coated CVCs or CVC removal at the study institution. All patients were treated with appropriate systemic antibiotics. The exchange group was matched in a 1:2 ratio with the removal group by organism, underlying disease, and neutropenia. The demographics, clinical characteristics, and outcome were compared. Overall response was defined as the resolution of clinical signs and symptoms and eradication of bacteremia within 72 hours after CVC exchange or removal, without disease recurrence or infection-related death. RESULTS: A total of 120 cancer patients were included (40 in the exchange group and 80 in the removal group). Overall response rates were 95% in the exchange group and 76% in the removal group (P = .011). No disease recurrences or infection-related deaths occurred in the exchange group; 8 disease recurrences or deaths (11%) occurred in the removal group (P = .05). Patients in the exchange group also experienced lower rates of mechanical failure (3% vs 15%; P = .049). CONCLUSIONS: Exchanging CVCs for MR-coated CVCs in cancer patients with CLABSIs may improve the overall response rate and decrease the risk of mechanical failure, disease recurrence, and infection-related mortality.

Multisystem crisis in a patient with presumptive renal cell carcinoma.

We describe the case of a patient who presented with a kidney lesion, lymphadenopathy, and bone metastasis. He developed a tetrad of high fever, encephalopathy, labile blood pressure, and multiple organ system failure. Initially, he was diagnosed with metastatic renal cell carcinoma (RCC). His fevers and encephalopathy were compatible with a putative paraneoplastic syndrome. Eventually, he was found to have malignant pheochromocytoma. To our knowledge, this is the first reported case of a malignant pheochromocytoma with multisystem crisis. Because of its atypical presentation and unusual findings, a high index of suspicion is necessary for the timely diagnosis of this clinical entity. Prompt diagnosis and appropriate treatments could improve the performance status and quality of life of such patients.