Neutropenic Enterocolitis: Clinical Features and Outcomes.

BACKGROUND: Patients undergoing chemotherapy are at risk for mucosal injury and neutropenia, which facilitate colonic mucosal invasion by the bowel flora and subsequent neutropenic enterocolitis, which has a poor prognosis. OBJECTIVE: This study aimed to assess the clinical features and outcomes of neutropenic enterocolitis in patients at a comprehensive cancer center. DESIGN: This is a retrospective cohort study. SETTING: The study was conducted at the University of Texas MD Anderson Cancer Center. PATIENTS: Neutropenic enterocolitis was defined by the presence of an absolute neutrophil count <1000/mm, compatible abdominal symptoms, and either mucosal thickening on abdominal imaging or mucosal injury on colon biopsy. Patients who had been diagnosed between 2010 and 2018 were included. MAIN OUTCOMES: Complication and survival rates were analyzed using logistic regression and Cox regression analyses, respectively. RESULTS: Of the 49,244 patients who had neutropenia during the study period, 134 (2.7%) were included. The median time from neutropenia onset to neutropenic enterocolitis was 2 days (interquartile range, 1-10 days). Neutropenic enterocolitis symptoms lasted for a median of 11 days (interquartile range, 6-22 days). Most patients received antibiotics (88%) and granulocyte colony-stimulating factor (68%). Complications included sepsis (11%), colonic perforation (2%), pneumatosis intestinalis (2%), and abscess formation (2%). The risks associated with complications included immunosuppressive therapy use within 1 month before neutropenic enterocolitis onset (OR, 3.92; 95% CI, 1.04-14.76) and delayed imaging (OR, 1.10; 95% CI, 1.03-1.17). Older age, severe neutropenia, prolonged neutropenia before and after neutropenic enterocolitis diagnosis, and other concomitant systemic infections were associated with lower survival rates. LIMITATIONS: The performance of this study at a single center and its retrospective nature are limitations of the study. CONCLUSION: The prompt diagnosis and management of neutropenic enterocolitis are critical to prevent complications. The use of granulocyte colony-stimulating factor can be beneficial to shorten the duration of neutropenia. See Video Abstract at http://links.lww.com/DCR/B116. ENTEROCOLITIS NEUTROPÉNICA: CARACTERÍSTICAS CLÍNICAS Y RESULTADOS: Los pacientes sometidos a quimioterapia, están en riesgo de lesión de la mucosa y neutropenia, lo que facilita la invasión de la mucosa colónica por la flora intestinal y la subsecuente enterocolitis neutropénica, con un mal pronóstico.Evaluar las características clínicas y los resultados de la enterocolitis neutropénica de pacientes en un centro integral de cáncer.Estudio de cohorte retrospectivo.El estudio se realizó en el MD Anderson Cancer Center de la Universidad de Texas.Se definió la enterocolitis neutropénica, como la presencia de un recuento absoluto de neutrófilos <1000 / mm3, con síntomas compatibles abdominales y engrosamiento de la mucosa en imagen abdominal o lesión de la mucosa en biopsia de colon. Se incluyeron pacientes diagnosticados entre 2010 y 2018.Se analizaron las tasas de complicaciones y supervivencia mediante análisis de regresión logística y regresión de Cox.De 49,244 pacientes que tuvieron neutropenia durante el período de estudio, 134 (2.7%) fueron incluidos. La media del tiempo desde el inicio de la neutropenia hasta la enterocolitis neutropénica, fue de 2 días (RIC, 1-10 días). Los síntomas de enterocolitis neutropénica duraron una media de 11 días (RIC, 6-22 días). La mayoría de los pacientes recibieron antibióticos (88%) y factor estimulante de colonias de granulocitos (68%). Las complicaciones incluyeron sepsis (11%), perforación colónica (2%), neumatosis intestinal (2%) y formación de abscesos (2%). Los riesgos asociados con las complicaciones incluyeron, uso de terapia inmunosupresora dentro de 1 mes antes del inicio de la enterocolitis neutropénica (razón de probabilidades 3.92; intervalo de confianza del 95% 1.04-14.76) y demora en la obtención de imágenes (razón de probabilidades 1.10; intervalo de confianza del 95% 1.03-1.17), edad avanzada, neutropenia grave, neutropenia prolongada antes y después del diagnóstico de enterocolitis neutropénica y de otras infecciones sistémicas concomitantes, se asociaron con bajas tasas de supervivencia.Centro único y estudio retrospectivo.El rápidodiagnóstico y manejo de la enterocolitis neutropénica, es crítico para prevenir complicaciones. El uso del factor estimulante de colonias de granulocitos puede ser beneficioso para acortar la duración de la neutropenia. Consulte Video Resumen en http://links.lww.com/DCR/B116.

Treating invasive aspergillosis in patients with hematologic malignancy: diagnostic-driven approach versus empiric therapies.

BACKGROUND: Early antifungal therapy for invasive aspergillosis (IA) has been associated with improved outcome. Traditionally, of empiric antifungal therapy has been used for clinically suspected IA. We compared outcomes of patients with hematologic malignancy and IA who were treated with voriconazole using the diagnostic driven DDA (DDA-Vori) that includes galactomannan testing vs. empiric therapy with a non-voriconazole-containing regimen (EMP-non-Vori) or empiric therapy with voriconazole (EMP-Vori). METHODS: We retrospectively reviewed the medical records of 342 hematologic malignancy patients diagnosed with proven, or probable IA between July 1993 and February 2016 at our medical center who received at least 7 days of DDA-Vori, EMP-Vori, or EMP-non-Vori. Outcome assessment included response to therapy (clinical and radiographic), all-cause mortality, and IA-attributable mortality. RESULTS: By multivariate analysis, factors predictive of a favorable response included localized/sinus IA vs. disseminated/pulmonary IA (p <  0.0001), not receiving white blood cell transfusion (p <  0.01), and DDA-Vori vs. EMP-non-Vori (p < 0.0001). In contrast, predictors of mortality within 6 weeks of initiating IA therapy included disseminated/pulmonary infection vs. localized/sinus IA (p < 0.01), not undergoing stem cell transplantation within 1 year before IA (p = 0.01), and EMP-non-Vori vs. DDA-Vori (p < 0.001). CONCLUSIONS: DDA-Vori was associated with better outcome (response and survival) compared with EMP-non-Vori and with equivalent outcome to EMP-Vori in hematologic malignancy patients. These outcomes associated with the implementation of DDA could lead to a reduction in the unnecessary costs and adverse events associated with the widespread use of empiric therapy.

Development of Gendine-Coated Cannula for Continuous Subcutaneous Insulin Infusion for Extended Use.

Continuous subcutaneous insulin infusion (CSII) using pumps is a widely used method for insulin therapy in patients with diabetes mellitus. Among the major factors that usually lead to the discontinuation of CSII are CSII set-related issues, including infection at the infusion site. The American Diabetic Association currently recommends rotating sites every 2 to 3 days. This recommendation adds cost and creates inconvenience. Therefore, in order to prevent infections and extend the duration between insertion site changes, we developed a Teflon cannula coated with a combination of gentian violet and chlorhexidine (gendine) and tested its antimicrobial efficacy against different pathogens. The cannulas were coated with gendine on the exterior surface and dried. The efficacy and durability of gendine-coated cannulas were determined against methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, methicillin-susceptible S. aureus, Streptococcus pyogenes, vancomycin-resistant enterococci, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Candida glabrata using a biofilm colonization method. The cytotoxicity of gendine was assessed against mouse fibroblast cell lines. The gendine-coated cannulas showed complete prevention of biofilm colonization of all organisms tested for up to 2 weeks (P < 0.0001) compared to that with the uncoated control. A gendine-coated catheter against mouse fibroblast cells was shown to be noncytotoxic. Our in vitro results show that a novel gendine cannula is highly effective in completely inhibiting the biofilm of multidrug-resistant pathogens for up to 2 weeks and may have potential clinical applications, such as prolonged use, cost reduction, and lower infection rate.

In vivo biocompatibility and in vitro efficacy of antimicrobial gendine-coated central catheters.

Antimicrobial peripherally inserted central catheters (PICCs) might reduce the incidence of central line-associated bloodstream infections (CLABSI). We tested the biocompatibility of a novel gendine-coated (combination of chlorhexidine [CHX] and gentian violet [GV]) PICC in a rabbit intravascular model and tested antimicrobial efficacy in comparison with commercially available minocycline/rifampin (M/R)- and CHX-treated PICCs in an in vitro biofilm colonization model. Gendine-coated and uncoated control PICCs were inserted in the jugular veins of rabbits for 4 days. Histopathological analysis was performed at the end of the 4-day period, and circulating levels of CHX and GV in the blood were measured at different time points using liquid chromatography-mass spectrometry. The antimicrobial efficacy of the PICCs was tested following simulated intravascular indwells of 24 h and 1 week against clinical isolates of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Enterobacter cloacae, Candida albicans, and Candida glabrata. Rabbits implanted with gendine-coated PICCs exhibited reduced levels of thrombosis and inflammation compared to those of the rabbits with uncoated controls. No GV was detected in blood samples over the entire study period, and trace concentrations of CHX were detected. The gendine-coated PICCs completely prevented the adherence of all pathogens from 24 h to 1 week (P ≤ 0.001), while M/R-treated, CHX-treated, and control PICCs did not. Gendine-coated PICCs were highly effective in preventing biofilm formation of multidrug-resistant pathogenic bacteria and fungi. Gendine-coated PICCs were biocompatible in an intravascular setting. Further, the pharmacokinetic testing established that acute systemic exposures of CHX and GV from the gendine-coated catheters were well within safe levels.

Prevention of biofilm colonization by Gram-negative bacteria on minocycline-rifampin-impregnated catheters sequentially coated with chlorhexidine.

Resistant Gram-negative bacteria are increasing central-line-associated bloodstream infection threats. To better combat this, chlorhexidine (CHX) was added to minocycline-rifampin (M/R) catheters. The in vitro antimicrobial activity of CHX-M/R catheters against multidrug resistant, Gram-negative Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia was tested. M/R and CHX-silver sulfadiazine (CHX/SS) catheters were used as comparators. The novel CHX-M/R catheters were significantly more effective (P < 0.0001) than CHX/SS or M/R catheters in preventing biofilm colonization and showed better antimicrobial durability.

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.

Comparing Molnupiravir to Nirmatrelvir/Ritonavir (Paxlovid) in the Treatment of Mild-to-Moderate COVID-19 in Immunocompromised Cancer Patients.

BACKGROUND: Nirmatrelvir/Ritonavir has been shown to reduce the risk of COVID-19 progression by 88% compared to placebo, while Molnupiravir reduced it by 31%. However, these two agents have not been compared head-to-head. We therefore compared the safety and efficacy of both agents for the treatment of mild-to-moderate COVID-19 in immunocompromised cancer patients. METHODS: We identified 240 cancer patients diagnosed with COVID-19 and treated with Molnupiravir or Nirmatrelvir/Ritonavir. Patients were matched using a 1:2 ratio based on age group (18-64 years vs. ≥65) and type of cancer. The collected data included demographics, comorbidities, and treatment outcome. RESULTS: Both groups had comparable characteristics and presenting symptoms. However, dyspnea was more prevalent in the Molnupiravir group, while sore throat was more prevalent in the Nirmatrelvir/Ritonavir group. The rate of disease progression was comparable in both groups by univariate and multivariable analysis. Treatment with Molnupiravir versus Nirmatrelvir/Ritonavir revealed no significant difference in disease progression by multivariable analysis (adjusted OR = 1.31, 95% CI: 0.56-3.14, p = 0.70). Patients who received Nirmatrelvir/Ritonavir, however, were significantly more prone to having drug-drug interactions/adverse events (30% vs. 0%, p < 0.0001). CONCLUSIONS: In the treatment of mild-to-moderate COVID-19 in cancer patients, Molnupiravir was comparable to Nirmatrelvir/Ritonavir in preventing progression to severe disease/death and rebound events, and it had a superior safety profile.

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.

Glyceryl trinitrate complements citrate and ethanol in a novel antimicrobial catheter lock solution to eradicate biofilm organisms.

Antimicrobial catheter lock therapy is practiced to prevent lumenal-sourced infections of central venous catheters. Citrate has been used clinically as an anticoagulant in heparin-free catheter locks. Ethanol has also been widely studied as an antimicrobial lock solution component. This study reports on the synergy of glyceryl trinitrate (GTN) with citrate and ethanol in rapidly eradicating methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans biofilms in an in vitro model for catheter biofilm colonization. GTN has a long history of intravenous use as a hypotensive agent. It is potentially attractive as a component of a catheter lock solution because its physiologic half-life is quite short and its metabolic pathways are known. A lock containing 7% citrate and 20% ethanol required 0.01% GTN to fully eradicate biofilms of all test organisms within 2 h in the model. This GTN concentration is below the levels where clinically significant hypotensive effects are expected.

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.

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.

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.

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.

Detection and control of a nosocomial respiratory syncytial virus outbreak in a stem cell transplantation unit: the role of palivizumab.

Respiratory syncytial virus (RSV) is a common community-acquired virus that causes upper and lower respiratory tract infections in children, hematologic malignancy patients, and hematopoietic stem cell transplant (HSCT) recipients. Nosocomial transmission of RSV in immunocompromised patients can significantly affect morbidity, mortality, and duration of hospitalization. Stringent infection control measurements are needed to control further hospital transmission. Prophylactic palivizumab was found to result in a significant reduction in hospitalization rates in high-risk children. In this article, we report a nosocomial outbreak of RSV in an adult HSCT unit (4 pods) from January 16 to February 4, 2004, including the infection control interventions used and the prophylactic administration of palivizumab in high-risk patients. Active surveillance identified 5 cases, a substantial increase from previous seasons (2 or 3 cases per season). All infected patients were isolated to 1 nursing pod and placed on contact isolation. All patients on the HSCT unit underwent rapid RSV antigen screening using nasal washes; this was repeated 1 week later, and 1 additional RSV case was identified. Patients identified to be at increased risk for RSV infection received prophylactic palivizumab. Routine screenings of the staff and visitors were undertaken. All patient and visitor areas were thoroughly cleaned with bleach. We educated health care workers about RSV transmission, highlighting proper hand hygiene and contact precautions. Four of 6 patients with RSV infection developed RSV pneumonia, and 2 of these patients died. Staff and visitors with upper respiratory symptoms were screened, and all were negative for RSV. Prophylactic palivizumab was administered in 16 patients who tested negative for RSV, but were considered to be at increased risk for RSV infection. None of these patients developed RSV infections. An RSV outbreak was controlled using prompt preventive measures, including cohorting patients, with a dedicated health care staff; contact isolation of patients; strict adherence to hand hygiene; and screening of visitors, family members, and health care staff for upper respiratory infection symptoms. Immunoprophylaxis with palivizumab, administered to high-risk patients, complemented strict infection control intervention. Thus, the role of palivizumab in the control of RSV hospital outbreaks merits further investigation.

Characteristics and outcomes of methicillin-resistant Staphylococcus aureus surgical-site infections in patients with cancer: a case-control study.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections remain a significant cause of morbidity and mortality. We experienced an increased incidence of MRSA surgical-site infections (MRSA SSIs) at our institution. However, to our knowledge, no studies have evaluated the risk factors and outcomes of MRSA SSIs in cancer patients. METHODS: We conducted a case-control study and identified all patients who had developed MRSA SSIs at our institution from July 1, 2002 to July 30, 2003, and all patients who had undergone surgery by the same surgical team during the same time period but who had not developed MRSA SSIs. Cases and controls were age-matched at 1:2 ratio. RESULTS: The study included 29 cases and 58 controls. Mean interval between surgery and MRSA SSI onset was 17.8 days (range 3-75 days). Cases were more likely than controls to have progressive cancer (72 versus 38%), have received antibiotics (mainly quinolones) within 24 h of surgery (17 versus 2%), have had ongoing infection (10 versus 0%), and have had longer hospital and intensive care unit stays (11.0 versus 7.8 days and 3.4 versus 1.5 days) (all P < 0.05). In a multivariate logistic regression analysis, significant predictors of MRSA SSI in cancer patients were antibiotics use <24 h of surgery and progressive cancer. No surgical factors (i.e., procedure time or timing of perioperative antibiotics) were associated with increased risk of MRSA SSI. CONCLUSIONS: Several clinical and postoperative factors were associated with increased risk of MRSA SSI in cancer patients, but antibiotic use before surgery (especially quinolones) and progressive cancer were the only independent predictors.

Differentiating culture samples representing coagulase-negative staphylococcal bacteremia from those representing contamination by use of time-to-positivity and quantitative blood culture methods.

Differentiating true coagulase-negative staphylococcal infection from contamination has an important impact on therapeutic implications. Time to positivity reflects bacterial density and may help in the interpretation of blood cultures. We retrospectively reviewed the records of 272 patients from June 2005 to January 2008 for clinical characteristics, microbiological data, and therapeutic outcome. Four groups were identified. The first three groups, as follows, included patients with one positive quantitative blood culture: the low-colony-count group (<10 CFU/ml), the moderate-colony-count group (30 to 100 CFU/ml), and the high-colony-count group (>100 CFU/ml). The control group included patients with two positive quantitative blood cultures and definite coagulase-negative staphylococcal bloodstream infection. The high-colony-count group had shorter time to positivity (< or = 16 h) than did the low-colony-count group (P < 0.0001). The low-colony-count group had a significantly longer time to positivity, >20 h (P = 0.001), than did the moderate-colony-count group. Even though antibiotics were not provided in 71% of cases and central venous catheter was retained in 83%, the low-colony-count group had a favorable outcome, suggesting that <10 CFU/ml represents contamination. The high-colony-count group, similar to the positive control group, required antibiotics in 81% of cases and central venous catheter removal in 51% (P = 0.001). A time to positivity of < or = 16 h reflects high-grade bacteremia with CFU of >100. Similar to the positive control group, these patients required an active therapeutic approach. A time to positivity of >20 h indicates possible contamination with a CFU of <10, and active therapy may not be required.

Role of ethylene diamine tetra-acetic acid (EDTA) in catheter lock solutions: EDTA enhances the antifungal activity of amphotericin B lipid complex against Candida embedded in biofilm.

Ethylene diamine tetra-acetic acid (EDTA) is an anticoagulant with antibiofilm-enhancing activity. We therefore used an in vitro biofilm model to determine the activity of amphotericin B lipid complex (ABLC) with or without EDTA against Candida embedded in biofilm on silicone disk surfaces. Clinical blood isolates from cancer patients infected with Candida albicans or Candida parapsilosis were used. Silicone disks were colonised with C. albicans or C. parapsilosis and were sequentially incubated in plasma and then in Mueller-Hinton broth containing 10(5) colony-forming units of each organism. All tests were performed in triplicate. The disks were subsequently placed and incubated for 6h and 8h in solutions containing ABLC alone, EDTA alone, ABLC+EDTA or broth (control). Disks were then removed, sonicated and colony counts were determined. ABLC+EDTA (30 mg/mL) was significantly more effective than ABLC, EDTA and control against C. parapsilosis at 6h (P < or = 0.01) and against C. albicans at 8h (P < or = 0.04). In patients with catheter-related candidaemia when catheter removal is not feasible, the combination of ABLC+EDTA may be considered for antifungal catheter lock solution as part of a catheter salvage therapy.

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.

Catheter-Related Staphylococcus aureus Bacteremia and Septic Thrombosis: The Role of Anticoagulation Therapy and Duration of Intravenous Antibiotic Therapy.

BACKGROUND: Catheter-related septic thrombosis is suspected in patients with persistent central line-associated bloodstream infection (CLABSI) after 72 hours of appropriate antimicrobial therapy. The clinical diagnosis and management of this entity can be challenging as limited data are available. We retrospectively studied the clinical characteristics of patients with Staphylococcus aureus catheter-related septic thrombosis and the outcomes related to different management strategies. METHODS: This retrospective study included patients with CLABSI due to S. aureus who had concomitant radiographic evidence of catheter site thrombosis treated at our institution between the years 2005 and 2016. We collected data pertaining to patients' medical history, clinical presentation, management, and outcome within 3 months of bacteremia onset. RESULTS: A total of 128 patients were included. We found no significant difference in overall outcome between patients who had deep vs superficial thrombosis. Patients with superficial thrombosis were found to have a higher rate of pulmonary complications (25% vs 6%; P = .01) compared with those with deep thrombosis. Patients who received less than 28 days of intravascular antibiotic therapy had higher all-cause mortality (31 vs 5%; P = .001). A multivariate logistic regression analysis identified 2 predictors of treatment failure: ICU admission during their illness (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.08-6.99; P = .034) and not receiving anticoagulation therapy (OR, 0.24; 95% CI, 0.11-0.54; P < .001). CONCLUSIONS: Our findings suggest that the presence of S. aureus CLABSI in the setting of catheter-related thrombosis may warrant prolonged intravascular antimicrobial therapy and administration of anticoagulation therapy in critically ill cancer patients.

Risk of bioaerosol contamination with Aspergillus species before and after cleaning in rooms filtered with high-efficiency particulate air filters that house patients with hematologic malignancy.

OBJECTIVE: To examine the impact of cleaning and directional airflow on environmental contamination with Aspergillus species in hospital rooms filtered with high-efficiency particulate air (HEPA) filters that house patients with hematologic malignancy. DESIGN: Detailed environmental assessment. SETTING: A 475-bed tertiary cancer center in the southern United States. METHODS: From April to October 2004, 1,258 surface samples and 627 bioaerosol samples were obtained from 74 HEPA-filtered rooms (in addition, 88 outdoor bioaerosol samples were obtained). Samples were collected from rooms cleaned within 1 hour after patient discharge and from rooms before cleaning. Positive and negative airflows were evaluated using air-current tubes at entrances to patient rooms. RESULTS: Of 1,258 surface samples, 3.3% were positive for Aspergillus species. Univariate analysis showed no relationship between cleaning status and occurrence of Aspergillus species. Of 627 bioaerosol samples, 7.3% were positive for Aspergillus species. Multiple logistic analysis revealed independently significant associations with detection of Aspergillus species. Cleaned rooms positive for Aspergillus species had a higher geometric mean density of colonies than that of rooms sampled before cleaning (18.9 vs 5.5 colony-forming units [cfu] per cubic meter; P=.0047). Rooms with positive airflow had a detection rate for bioaerosol samples equivalent to that of rooms with negative airflow (7.3% vs 7.8%; P=.8). There was no significant difference in the density of Aspergillus species between rooms with negative airflow and rooms with positive airflow (12.5 vs 8.4 cfu/m(3); P=.33). CONCLUSIONS: Concentration of bioaerosol contamination with Aspergillus species was increased in rooms sampled 1 hour after cleaning compared with rooms sampled before cleaning, suggesting a possible correlation between re-entrained bioaerosols (ie, those suspended by activity in the room) after cleaning and the risk of nosocomial invasive aspergillosis.