Catherine Chen

An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia: impact of multidrug resistance

IntroductionPseudomonas aeruginosa nosocomial pneumonia (Pa-NP) is associated with considerable morbidity, prolonged hospitalization, increased costs, and mortality.MethodsWe conducted a retrospective cohort study of adult patients with Pa-NP to determine 1) risk factors for multidrug-resistant (MDR) strains and 2) whether MDR increases the risk for hospital death. Twelve hospitals in 5 countries (United States, n = 3; France, n = 2; Germany, n = 2; Italy, n = 2; and Spain, n = 3) participated. We compared characteristics of patients who had MDR strains to those who did not and derived regression models to identify predictors of MDR and hospital mortality.ResultsOf 740 patients with Pa-NP, 226 patients (30.5%) were infected with MDR strains. In multivariable analyses, independent predictors of multidrug-resistance included decreasing age (adjusted odds ratio [AOR] 0.91, 95% confidence interval [CI] 0.96-0.98), diabetes mellitus (AOR 1.90, 95% CI 1.21-3.00) and ICU admission (AOR 1.73, 95% CI 1.06-2.81). Multidrug-resistance, heart failure, increasing age, mechanical ventilation, and bacteremia were independently associated with in-hospital mortality in the Cox Proportional Hazards Model analysis.ConclusionsAmong patients with Pa-NP the presence of infection with a MDR strain is associated with increased in-hospital mortality. Identification of patients at risk of MDR Pa-NP could facilitate appropriate empiric antibiotic decisions that in turn could lead to improved hospital survival.

Targeted Fluid Minimization Following Initial Resuscitation in Septic Shock: A Pilot Study.

BACKGROUND IV fluid represents a basic therapeutic intervention for septic shock. Unfortunately, the optimal administration of IV fluid to maximize patient outcomes and prevent complications is largely unknown. METHODS Patients with septic shock admitted to the medical ICUs of Barnes-Jewish Hospital (January to December 2014) requiring vasoactive agents for at least 12 h following initial fluid resuscitation were randomized to usual care or to targeted fluid minimization (TFM) guided by daily assessments of fluid responsiveness. RESULTS Eighty-two patients were enrolled, 41 to usual care and 41 to TFM. For patients randomized to TFM, the net median (interquartile range) fluid balance was less at the end of day 3 (1,952 mL [48-5,003 mL] vs 3,124 mL [767-10,103 mL], P = .20) and at the end of day 5 (2,641 mL [-1,837 to 5,075 mL] vs 3,616 mL [ -1,513 mL to 9,746 mL], P = .40). TFM appeared to be safe, as indicated by similar clinical outcomes including in-hospital mortality (56.1% vs 48.8%, P = .51), ventilator days (8.0 days [3.25-15.25 days] vs 5.0 days [3.0-9.0 days], P = .30), renal replacement therapy (41.5% vs 39.0%, P = .82), and vasopressor days (4.0 days [2.0-8.0 days] vs 4.0 days [2.0-6.0 days], P = .84). CONCLUSIONS This pilot study suggests that TFM in patients with septic shock can be performed using protocol-guided assessments of fluid responsiveness. Larger trials of TFM in septic shock are needed. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT02473718; URL: www.clinicaltrials.gov.

Pseudomonas aeruginosa nosocomial pneumonia: impact of pneumonia classification

OBJECTIVE To describe and compare the mortality associated with nosocomial pneumonia due to Pseudomonas aeruginosa (Pa-NP) according to pneumonia classification (community-onset pneumonia [COP], hospital-acquired pneumonia [(HAP], and ventilator-associated pneumonia [VAP]). DESIGN We conducted a retrospective cohort study of adults with Pa-NP. We compared mortality for Pa-NP among patients with COP, HAP, and VAP and used logistic regression to identify risk factors for hospital mortality and inappropriate initial antibiotic therapy (IIAT). SETTING Twelve acute care hospitals in 5 countries (United States, 3; France, 2; Germany, 2; Italy, 2; and Spain, 3). PATIENTS/PARTICIPANTS A total of 742 patients with Pa-NP. RESULTS Hospital mortality was greater for those with VAP (41.9%) and HAP (40.1%) compared with COP (24.5%) (P<.001). In multivariate analyses, independent predictors of hospital mortality differed by pneumonia classification (COP: need for mechanical ventilation and intensive care; HAP: multidrug-resistant isolate; VAP: IIAT, increasing age, increasing Charlson comorbidity score, bacteremia, and use of vasopressors). Presence of multidrug resistance was identified as an independent predictor of IIAT for patients with COP and HAP, whereas recent antibiotic administration was protective in patients with VAP. CONCLUSIONS Among patients with Pa-NP, pneumonia classification identified patients with different risks for hospital mortality. Specific risk factors for hospital mortality also differed by pneumonia classification and multidrug resistance appeared to be an important risk factor for IIAT. These findings suggest that pneumonia classification for P. aeruginosa identifies patients with different mortality risks and specific risk factors for outcome and IIAT.

Hyperammonemia Syndrome After Lung Transplantation: A Single Center Experience.

Background Hyperammonemia is a rare, often fatal complication after transplantation. The etiology is unknown, but recognition and rapid treatment may help to improve the survival of this unusual syndrome. We present the largest case series to date of hyperammonemia after lung transplantation (LTx) and discuss a treatment protocol that has been developed at our institution. Methods We conducted a retrospective cohort series of patients who underwent LTx between January 1, 2000, and December 31, 2013. Patients who developed hyperammonemia syndrome in the posttransplantation period, which was defined as symptoms of encephalopathy and plasma ammonia level exceeding 200 &mgr;mol/L on at least 1 occasion, were included. Data including demographics, antimicrobial and immunosuppression regimens, ammonia levels and other pertinent laboratory data, treatments administered, and outcomes were recorded. Results Eight of 807 lung transplant recipients developed hyperammonemia syndrome postoperatively during this time period. Median time to onset was 9.0 days, and median peak ammonia level was 370 &mgr;mol/L. All 8 patients were treated with hemodialysis, 7 of 8 patients were treated with bowel decontamination, and 5 of 8 patients were treated with nitrogen scavenging agents. Six of the 8 patients died. Conclusions The incidence of hyperammonemia syndrome in LTx patients was approximately 1%. Future research is needed to determine the efficacy of treatment, including hemodialysis, bowel decontamination, antibiotics, and the use of nitrogen scavenging agents in lung recipients with hyperammonemia.

Conservative fluid therapy in septic shock: an example of targeted therapeutic minimization

Intravenous fluids (IVFs) represent a basic therapeutic intervention utilized in septic shock. Unfortunately, the optimal method for administering IVFs to maximize patient outcomes is unknown. A meta-analysis of four randomized trials of goal-directed therapy did not demonstrate a significant reduction in mortality (odds ratio 0.609; 95% confidence interval 0.363 to 1.020; P = 0.059), whereas 18 trials with historical controls showed a significant increase in survival (odds ratio 0.580; 95% confidence interval 0.501 to 0.672; P < 0.0001). Based on these data, clinicians should be aware of the potential for harm due to the excessive administration of IVFs to patients with septic shock.

Thromboelastometry analysis of severe North American pit viper-induced coagulopathy: A case report

Case details: A 51‐year‐old man presented with rapid onset encephalopathy and respiratory failure after a suspected intravascular envenomation from a North American pit viper. The patient received antivenom and was transferred to a tertiary care facility where he had cardiovascular collapse and persistent coagulopathy requiring 28 vials of Crotalidae polyvalent immune Fab antivenom for initial control and six vials for maintenance. The patients coagulopathy was monitored using “traditional” measures (platelets, fibrinogen, and prothrombin time/international normalized ratio) and rotational thromboelastometry (ROTEM®). The patient also subsequently developed intestinal necrosis requiring exploratory laparotomy with ileum and colonic resections, and anuric renal failure requiring continuous renal replacement therapy. After coordinated multidisciplinary management, he was discharged to an acute inpatient rehabilitation on hospital day 25 and has since made a full recovery. Discussion: In the setting of a severe intravascular pit viper envenomation, thromboelastometry correlated well with “traditional” measures. During recovery, ROTEM® demonstrated measurable improvements in the extrinsic coagulation pathway while the INR remained between 1.5 and 1.6. Patients intestinal necrosis may have resulted from microvascular thrombosis due to Crotalinae venom. The patients ultimate recovery necessitated a coordinated multidisciplinary effort. ROTEM® abnormalities after North American pit viper envenomation may be more sensitive than “traditional” measures and may have prognostic value to determine the severity of envenomation, but further research to define its utility is required. HighlightsA severe North American pit viper envenomation resulted in cardiovascular collapse, intestinal necrosis, and renal failure.Use of rotational thromboelastometry (ROTEM®) correlates well with measurements of fibrinogen and prothrombin time/INR.EXTEM specification may be more sensitive than INR alone in evaluating extrinsic pathway abnormalities.

Copy number variations in a population with prune belly syndrome

Prune Belly Syndrome (PBS) is a congenital multisystem myopathy with mild to lethal severity. While of uncertain etiology, 95% male predominance and familial occurrence suggest a genetic basis. As copy number variations (CNVs) can cause unexplained genetic disorders, we tested for novel CNVs in a large PBS population. We genotyped 21 unrelated PBS patients by high‐resolution array comparative genomic hybridization (aCGH) and phenotyped using a novel PBS severity scoring system. Available parents were screened for detected CNV via quantitative PCR (qPCR). We additionally screened for recurrence of identified novel candidate CNVs on 106 PBS probands by qPCR. We identified 10 CNVs in 8 of 21 PBS patients tested (38%). Testing confirmed inheritance from an unaffected biological parent in six patients; parental samples were unavailable in two probands. One candidate CNV includes duplication of the X‐chromosome AGTR2 gene, known to function in urinary tract development. Subsequent screening of the larger PBS cohort did not identify any recurrent CNVs. Presence of CNV did not correlate with PBS severity scoring. CNVs were uncommon in this large PBS population, but analysis of identified variants may inform disease pathogenesis and reveal targets for therapeutic intervention for this rare, severe disorder.

Identical Twins, Matching Symptoms: Hypersensitivity Pneumonitis

PRESENTATION Shortness of breath was first attributed to the patient’s extensive history of cardiac ills, but a detailed environmental history pointed to the true source. A 58-year-old Caucasian woman presented with a 12-month history of dyspnea, nonproductive cough, and wheezing. She had been born with Ebstein’s anomaly, for which she had undergone tricuspid valve replacement with a prosthetic valve and repair of a coexisting atrial septal defect. In addition, she had an implanted pacemaker for complete heart block. Her cardiologist was considering biventricular pacing as an intervention for her dyspnea and requested a pulmonary evaluation before proceeding. The patient, who was married and a nurse, had an unremarkable pulmonary history. None of her medications posed a risk for lung toxicity. She never smoked, drank alcohol, or used illicit drugs. An identical twin sister, who lived in Texas, had similar pulmonary complaints and a presumptive diagnosis of pulmonary fibrosis. The sister’s medical records were brought to the consultation due to concern for a genetic predisposition for this progressive lung disease.

339An International, Multicenter, Retrospective Study of Nosocomial Pneumonia due to Pseudomonas aeruginosa

339. An International, Multicenter, Retrospective Study of Nosocomial Pneumonia due to Pseudomonas aeruginosa Scott Micek, PharmD; Richard Wunderink, MD; Catherine Chen, MD; Jean E. Chastre, MD; Marin Kollef, MD; Pharmacy Practice, St. Louis College of Pharmacy, St. Louis, MO; Northwestern University Feinberg School of Medicine, Chicago, IL; Washington University School of Medicine, St. Louis, MO; Jordi Rello, MD, Hospital Vall D’Hebron, Barcelona, Spain; Reanimation Medicale, PitieSalpetriere Hospital, Paris, France; Vandana Menon, MD, Cubist Pharmaceuticals, Inc., Lexington, MA; Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO and Investigators of the International Study of Nosocomial Pneumonia due to Pseudomonas aeruginosa