tbuckley/cabot-search huggingface dataset:
Use of genetic variants in wnt signaling pathway to predict gender and tumor location dependent survival in metastatic colorectal cancer (mCRC) patients (pts) treated with first-line FOLFIRI and bevacizumab (BEV).
Authors: Yan Ning, Wu Zhang, Dongyun Yang, Fotios Loupakis, Takeru Wakatsuki, Sebastian Stintzing, Nico Benjamin Volz, Joseph Ethan Li, Rita Elie El-Khoueiry, Melissa Janae Labonte, Chiara Cremolini, Federica Marmorino, Afsaneh Barzi, Anthony B. El-Khoueiry, Heinz-Josef Lenz, Michael Kahn
Journal: Journal of Clinical Oncology (2013)

3568 Background: CRC is generally characterized by aberrant Wnt signaling. Wnt signaling pathway genes AXIN2 and TCF7L2 complex control the proliferation and differentiation of intestinal epithelial cells. Previous study showed polymorphisms in TCF7L2 and AXIN2 were associated with increase risk of colon cancer. We tested the hypothesis whether single nucleotide polymorphisms (SNPs) in TCF7L2 (rs7903146) and AXIN2 (rs2240308, rs3923087) will predict clinical outcome in a cohort of mCRC pts treated with first line FOLFIRI/BEV. Methods: Genomic DNA were extracted from blood of 455 mCRC pts which prospectively enrolled in a pharmacogenetic translational study. Females(n=172) and males(n=252); Median follow up is 24 months, median PFS and OS were 10.5 and 29.9 months, respectively. Candidate SNPs were analyzed by PCR-based direct sequencing. Results: In the overall population analysis, TCF7L2 and AXIN2 polymorphisms were not associated with OS and PFS, but our data showed that 2 polymorphisms may predict clinical outcome when adjusted by pts gender and tumor location: 1) In right-sided tumors, male pts with any T allele of TCF7L2rs7903146 were associated with significantly worse PFS in comparison to those carrying C/C genotype (HR: 2.15; 95% CI: 1.09-4.22; P = 0.027, log-rank test). However, female pts with any T allele reversly showed better PFS compared with those carrying C/C variants (HR: 0.39; 95% CI: 0.17-0.94; P = 0.035, logrank test). 2) In women, pts with AXIN2 rs2240308 any A allele had better PFS and OS in right-sided tumors compared to those with any A allele but located in left side(p interaction =0.047)(PFS) and (p interaction =0.025)(OS), respectively. Conclusions: Our data show for the first time Wnt signaling pathway gene polymorphisms TCF7L2 rs7903146 and AXIN2 rs2240308 may predict PFS and OS in mCRC pts treated with first-line FOLFIRI/BEV. More importantly, this predictive value is dependent on gender and tumor location, suggesting a different role of Wnt signaling in female vs male and in right vs left side tumor. Our preliminary data warrants clinical trial validation.
Extensive Subcutaneous Foreign Body Granulomas Associated With “Skin Popping” Demonstrated on 18F-FDG PET/CT
Authors: Danijela Dejanovic, Annemarie Gjelstrup Amtoft
Journal: Clinical Nuclear Medicine (2020)

In illicit drug use, "skin popping" refers to the method of administering drugs by injecting it into the subcutaneous tissue. "Skin popping" can lead to acute and chronic skin manifestations caused by the drug itself and/or by the various adulterants and fillers commonly added to drug substances. Chronic skin manifestations include a foreign-body reaction with formation of granulomas at the site of injection. We present the F-FDG PET/CT findings of extensive subcutaneous granulomas in a 58-year-old woman with a heroin addiction undergoing treatment for infective endocarditis of the mitral valve.
CHANGES IN RIGHT ATRIAL STRAIN FOLLOWING PULMONARY THROMBOENDARTERECTOMY IN PATIENTS WITH CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION
Authors: Andrew Peters, Ashwin Shaan Madhan, Olga Kislitsina, Benjamin Freed, Daniel R. Schimmel, Michael J. Cuttica, S. Chris Malaisrie, James Thomas
Journal: Journal of the American College of Cardiology (2020)
PERIVASCULAR ADIPOSE TISSUE INFLAMMATION ON CORONARY COMPUTED TOMOGRAPHY IN PATIENTSWITH VASOSPASTIC ANGINA PERIVASCULAR ADIPOSE TISSUE INFLAMMATION ON CORONARY COMPUTED TOMOGRAPHY IN PATIENTSWITH VASOSPASTIC ANGINA
Authors: Hiroki Ueno, Masahiro Hoshino, Tomoyo Sugiyama, Yoshihisa Kanaji, Masao Yamaguchi, Yohei Sumino, Masahiro Hada, Toru Misawa, Hidenori Hirano, Tomoki Horie, Kai Nogami, Tsunekazu Kakuta
Journal: Journal of the American College of Cardiology (2020)
L-LEUCINE: A NOVEL BIOMARKER THAT PREDICTS LOWER MORTALITY IN PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Manasi Tannu, Sneha Gadi, Aditi Nayak, Chang Liu, Anurag Mehta, Ayman S. Tahhan, Yi-An Ko, Karan Uppal, Dean Jones, Javed Butler, Alanna Morris, Arshed A. Quyyumi
Journal: Journal of the American College of Cardiology (2020)
A randomized phase II study of bevacizumab (B) and gemcitabine (G) plus cetuximab (C) or erlotinib (E) in patients (pts) with advanced pancreatic cancer (PC): A preliminary analysis
Authors: H. L. Kindler, K. A. Bylow, H. S. Hochster, G. Friberg, K. Micetich, G. Locker, M. Kozloff, M. Moore, W. Sun, E. E. Vokes
Journal: Journal of Clinical Oncology (2006)

4040 Background: In a phase II trial of G + anti-VEGF antibody B in 52 PC pts, we reported a 21% response rate and median survival of 8.8 months (mo) (Kindler, JCO 2005). EGFR inhibitors C and E also have activity in PC. VEGF and EGFR pathways are interdependent; dual inhibition may be synergistic. Methods: We are conducting a multi-center, randomized phase II trial of GBC vs. GBE in advanced PC pts who have: no prior therapy for metastatic disease, PS 0–2, measurable disease, no tumor invasion of duodenum, no bleeding risk. Primary endpoint: response. Trial design: 2 parallel, Simon 2-stage designs; requires 6 responses in 27 evaluable pts for 2 nd stage; 63 pts/arm. All pts receive G 1000 mg/m 2 over 30 minutes days (D) 1, 8, 15 Q28D; B 10 mg/kg D 1, 15 Q28D. Pts are randomized to C 400 mg/m 2 D1, then 250 mg/m 2 Q7D, or E 150 mg D1–5, 8–12, 15–26 Q28D. CT scans: Q2 cycles. 58 pts enrolled at 13 sites 9/04–12/05. Pt characteristics: male 66%; median age 61 (range 36–82); PS: 0/1/2: 52%/40%/8%; stage IV 95%; liver metastases 76%. Results: 49 pts (GBC/GBE 24/25) are evaluable for toxicity; 51 pts (27/24) for response. 232 cycles were administered (median 4, range 1–11). Grade ¾ toxicity (%pts GBC/GBE): neutropenia 29%/28%; anemia 4%/16%, thrombocytopenia 8%/24%, DVT-PE 17%/8%, CVA 4%/4%, GI bleed 4%/12%, hypertension 4%/4%, rash 13%/4%, pneumonitis 0%/8%, diarrhea 4%/4%; grade 5: bowel perforation 0%/4%, MI- CVA 0%/4%, other cardiac 4%/0%. Response: GBC 19% (1 complete, 4 partial), GBE 21% (5 partial). Stable disease 59%/67%. Median progression-free survival 3.6/3.6 mo (95%CI: 2.7, 4.7/2.7, 5.9), 6-month survival 41%/38% (95% CI: 11%, 71%/2%, 75%). Conclusion: GBC and GBE are active in advanced PC. Toxicity, principally related to B, is moderate. The trial proceeds to a 2 nd stage if 1 more response is observed in each arm. Supported by NCI grant N01-CM-17102. [Table: see text]
Electronic medical record (EMR) in the oncology setting tested: A first hand experience
Authors: E. L. Hesita
Journal: Journal of Clinical Oncology (2006)

16043 Background: Current data indicate that America’s medical system has been slow to embrace technology in relation to the use of the electronic medical record (EMR). The disruption caused by hurricane Katrina in the lives of cancer patients living in the city of New Orleans may prove to be an eye-opening experience that will persuade healthcare providers to change the traditional way of storing medical records. This study focuses on the experience of displaced New Orleans cancer patients. Methods: An anonymous validated questionnaire was completed by a random group of returning patients six weeks after the hurricane. This random group of patients evacuated to various states across the country. The focal questions asked were: the degree of difficulty in obtaining records, whether the alternate oncologist had to order further test(s), and whether the patients agree to having their medical records in an electronic format. Results: Of the total of 75 respondents, 93% are served by an institution in the New Orleans area that utilizes EMR while 7% are served by various institutions within the New Orleans area that do not have EMR. Overall, 81% stated ease in obtaining their records (within 1–4 days) while 19% stated difficulty (7 days or greater). Only 3% of the patients with EMR indicated difficulty while 100% of the non-EMR patients stated difficulty. For patients with EMR, 83% of the alternate oncologists did not order further tests, while 100% of the alternate oncologists ordered further testing for patients without EMR. In terms of patients’ sentiments regarding EMR, 76% agree to have EMR while 24% disagree. Conclusions: EMR in the oncology setting may prove to be an essential component in the delivery of quality patient care in terms of safety, cost effectiveness, and preservation of privacy. The majority of the patients surveyed agree to a form of electronic record-keeping based on their first-hand experience. No significant financial relationships to disclose.
PROVIDE-HF STUDY RESULTS: PATIENT-REPORTED OUTCOMES INVESTIGATION FOLLOWING INITIATION OF DRUG THERAPY WITH ENTRESTO (SACUBITRIL/VALSARTAN) IN HEART FAILURE
Authors: Robert John Mentz, Haolin Xu, Emily Claire O'Brien, Laine Thomas, Tamas Alexy, Bhanu Gupta, Juan Vilaro, Anuradha (Anu) Lala, Ravi Dhingra, Alexandros Briasoulis, Marc A. Simon, Josef Stehlik, Jo Rodgers, Shannon Dunlay, Martha Abshire, Quinn Wells, Kurt G. Barringhaus, Peter Eckman, Brian Lowes, Johana Espinoza, Rosalia Blanco, Xian Shen, Carol Duffy, Adrian Hernandez
Journal: Journal of the American College of Cardiology (2020)
Recombinant adenoviral human p53 gene combined radio- and chemotherapy after a tumorectomy in treatment of laryngeal carcinoma in advanced stage.
Authors: Fei Chen, Feng Wang
Journal: Journal of Clinical Oncology (2013)

6050 Background: To investigate the benefits of post-surgery using recombinant adenoviral human p53 gene (rAd-p53) combined with radio- and chemo-therapy in treatment of laryngeal carcinoma in advanced stage. Methods: A total of 61 patients with a stage III or IV laryngeal cancer, 51 males and 10 females with an average age of 63.2, were randomly divided into three groups: G1, G2 and G3. The 18 G1 patients received no treatment after surgery. The patients in G2 (21 patients) and G3 (22 patients) received rAd-p53 followed by radio-and chemo-therapy, and only radio- and chemo-therapy, respectively. The rAd-p53 was injected into the surgery wound bed at a dose of 2 x 10 12 viral particles (VP) once per 3 days for 5 times. Radiotherapy was given at a total dose of 63-67 Gy in 7 weeks. The chemo-regimen included 5- Fu 500 mg/ m2 from day 1 to day 5 and DDP 30 mg / m2 from day 1 to day 3 in a treatment course of 21days for two courses. Results: All the study patients were followed up for at least 3 years. One patient in G2 lost to follow up. The local control rates (no recurrence) at 3 years were 38.9% (7/18), 75.0% (15/20), and 54.5% (12/22) for G1, G2, and G3, respectively. The 3-years progress free survivals (PSF) were 38.9%, 50.0%, and 45.0% for G1, G2, and G3, respectively. The 3-years overall survivals (OS) were 38.9%, 65.0%, and 45.0% for G1, G2, and G3, respectively. The three efficacy endpoints of G2 were significantly better than both G1 and G3. These efficacy measures of G3 were significantly higher than G1. Conclusions: Post-surgery chemo- and radiotherapy is necessary to increase the local control rate, prolong both PRF and OS. The rAd-p53 gene therapy can farther increase the efficacy measures.
THE FINAL FRONTIER: RATES OF NEW PERMANENT PACEMAKER PLACEMENT BETWEEN TRANSCATHETER AND SURGICAL AORTIC VALVE REPLACEMENT IN THE UNITED STATES, INSIGHTS FROM THE NATIONWIDE INPATIENT SAMPLE
Authors: Richard Hajjar, Adamantios Tsangaris, Hassan Arshad, Ahmad Alkhalil, Tilak Pasala
Journal: Journal of the American College of Cardiology (2020)
Leptin mediates postprandial increases in body temperature through hypothalamus–adrenal medulla–adipose tissue crosstalk
Authors: Rachel J. Perry, Kun Lyu, Aviva Rabin-Court, Jianying Dong, Xiruo Li, Yunfan Yang, Hua Qing, Andrew Wang, Xiaoyong Yang, Gerald I. Shulman
Journal: Journal of Clinical Investigation (2020)

Meal ingestion increases body temperature in multiple species, an effect that is blunted by obesity. However, the mechanisms responsible for these phenomena remain incompletely understood. Here we show that refeeding increases plasma leptin concentrations approximately 8-fold in 48-hour-fasted lean rats, and this normalization of plasma leptin concentrations stimulates adrenomedullary catecholamine secretion. Increased adrenal medulla-derived plasma catecholamines were necessary and sufficient to increase body temperature postprandially, a process that required both ﻿fatty acids generated from adipose tissue lipolysis and β-adrenergic activation of brown adipose tissue (BAT). Diet-induced obese rats, which remained ﻿relatively hyperleptinemic while fasting, did not exhibit fasting-induced reductions in temperature. To examine the impact of feeding-induced increases in body temperature on energy balance, we compared rats fed chronically by either 2 carbohydrate-rich boluses daily or a continuous ﻿isocaloric intragastric infusion. Bolus feeding increased body temperature and reduced weight gain compared with continuous feeding, an effect abrogated by treatment with atenolol. In summary, these data demonstrate that leptin stimulates a hypothalamus-adrenal medulla-BAT axis, which is necessary and sufficient to induce lipolysis and, as a result, increase body temperature after refeeding.
A NOVEL GENOTYPE-PHENOTYPE RISK PREDICTION MODEL FOR ARRHYTHMIC EVENTS IN WOMEN WITH LONG-QT SYNDROME
Authors: Ayhan Yoruk, David Huang, Anita Chen, Scott McNitt, Valentina Kutyifa, Arwa Younis, Bronislava Polonsky, Mehmet Aktas, Wojciech Zareba, Ilan Goldenberg
Journal: Journal of the American College of Cardiology (2020)
16O Phase I study of CC-90010, a reversible, oral BET inhibitor in patients (Pts) with advanced solid tumors (STs) and relapsed/refractory non-Hodgkin lymphoma (R/R NHL)
Authors: V. Moreno, I. Braña, J.M. Sepulveda Sanchez, M. Vieito Villar, T. Hernández Guerrero, B. Doger, O. Saavedra, A. Pinto, C. Carlo Stella, A. Italiano, J-M. Michot, G. Musuraca, R. Sarmiento, J. De Alvaro, M. Zuraek, T. Sánchez-Pérez, I. Aronchik, E. Filvaroff, B. Hanna, Z. Nikolova
Journal: Annals of Oncology (2020)
The role of FSH in castration-induced adipogenesis: Highlighting differences between orchiectomy, GNRH agonists, and antagonists.
Authors: Jehonathan H Pinthus, Sarah Hopmans, Wilhelmina Duivenvoorden, Anil Kapoor
Journal: Journal of Clinical Oncology (2013)

e16011 Background: Androgen deprivation therapy (ADT) results in weight gain and development of the metabolic syndrome. Inspired by the observation that adiposity accompanies the incremental increase in serum FSH levels in menopause, we hypothesized that GNRH antagonist which lower FSH levels will associate with reduced adiposity as compared to GNRH analogues and orchiectomy. Methods: 3T3-L1 fibroblasts differentiation into adipocytes and intracellular lipid accumulation were examined in the presence of escalating FSH doses (0-1000 IU/L) in charcoal stripped FCS supplemented medium to simulate castration. Cellular lipogenesis was assessed by image analysis (oil red staining) and by immunoblotting for fatty acid synthase (FAS) expression. In vivo, 6-week old C57Bl/6 male mice (n=30) were divided to receive either: orchiectomy + vehicle, sham procedure + vehicle, orchiectomy + GNRH antagonist (degarelix 50 mg/kg in vehicle), sham + degarelix, orchiectomy + GNRH analogue (enantone 2 mg/kg in vehicle), or sham + enantone. Serum testosterone, LH and FSH levels and differences in animal weight, visceral fat mass (VFm) and liver lipogenesis (oil red staining) were determined following sacrifice at 6 weeks. BMI was measured as weight (gr) divided by the distance between the tail root and the lower incisors (cm2). Results: The mean lowest and highest serum FSH levels were recorded in mice treated with Degarelix vs. orchiectomy (0.43 and 0.935 mIU/mL resp,) and the mean lowest and highest serum testosterone levels were in mice treated with orchiectomy+degarelix vs. sham control (0.12 and 13.1 ng/ml resp). Mice treated with degarelix had a significantly lower BMI compared to enantone (p=0.02). VFm (perirenal fat weight) was significantly lower (p=0.035) in mice castrated by degarelix (mean 0.38gr) as compared to enantone(mean 0.47gr)). Addition of degarelix or enanton to orchiectomy increased the differences in VFm and BMI between the two groups (0.12gr vs. 0.47gr and 3.73 vs. 4.29 gr/cm2 resp.) In vitro, FSH increased lipid accumulation and FAS expression in 3T3-L1 cells. Conclusions: FSH level elevation following castration promotes fat accumulation and weight gain in preclinical models.
Prognostic factors in patients (pts) with mediastinal nonseminomatous germ cell tumors (MNGCT).
Authors: Anatoly Bulanov, Mikhail Fedyanin, Alexey Tryakin, Ilya Pokataev, Tatiana Zakharova, Boris Polockii, August Garin, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2013)

e15585 Background: According to IGCCCG, pts with MNGCT belong to poor prognostic group. But, there are no independent prognostic factors which could determine prognosis in this group of pts. We retrospectively studied prognostic factors in pts with MNGCT. Methods: We analyzed data on 61 pts with MNGCT, who were treated in our department during 1986-2011. Median age was 23 years (range: 18-44). Median follow-up time was 52 months (range 4-180). Biopsy was performed in 35/61 (57.4%) pts before treatment. At the beginning of therapy median AFP was 3,360 IU/ml (range: 1-300,000), HCG – 4.5 mIU/ml (range: 0.1 to 326210), LDH – 791 U/l (range: 249-4,475). Conventional induction chemotherapy (CT): classical BEP regimen – 23 (37.8%) pts, T-BEP – 17 (27.8%) pts, CPOB – 17 (27.8%) pts, accelerated (two-weekly) BEP – 4 (6.6%) pts. After CT, residual tumor was resected in 28 (45.9%) pts. Multivariate Cox regression analysis was performed to determine independent factors, which influenced on overall survival (OS). Results: Marker-negative objective response was revealed in 40/61 (65.6%). Progression disease during induction CT was detected in 21 (34.4%) pts. 5-years OS was 44% for all pts. Multivariate analysis revealed the following independent negative prognostic factors: age ≥ 24 (р=0.08, HR 1.9, 95%CI 0.92-4.1), size of the primary mediastinal tumor ≥ 19 cm (р= 0.03, HR 5.8, 96%CI 1.85-18.67). Median OS hasn’t been reached and 3-year OS was 62% in pts with good prognosis (age &lt; 24 years and/or size of mediastinal tumor &lt; 19 cm) vs. 15 months and 30% in pts with poor prognosis (р=0.02, HR 0.42, 95%CI 0.19-0.87) respectively. Conclusions: Age ≥ 24 and size of the primary mediastinal tumor ≥ 19 cm are independent negative prognostic factors in pts with MNGCT. These factors could be used as strata in clinical trials. However, this tendency has to be confirmed in large series of pts.
Robustness of circadian rest-activity rhythm for predicting efficacy of intravenous cetuximab (Cet) and hepatic artery infusion (HAI) of chronomodulated irinotecan, 5-fluorouracil and oxaliplatin (Chrono-Optiliv) for liver metastases from colorectal cancer (LM-CRC) (Optiliv translational study, NCT00852228).
Authors: Abdoulaye Karaboué, Pasquale F. Innominato, Mohamed Bouchahda, Magali Mocquery, Rachel Bossevot, Virginie Plessis, Davina Bouchoucha, Rene Adam, Francis Levi
Journal: Journal of Clinical Oncology (2013)

e20519 Background: The rest-activity rhythm is a biomarker of the circadian timing system, whose disruption both accelerates cancer progression in experimental models (Filipski et al. JNCI 2002, 2005) and predicts for poor overall survival in cancer patients (pts) (Innominato et al. Cancer Res 2009; Int J Cancer 2012). Here we investigate the relevance of early signals of circadian disruption for the antitumor efficacy of intravenous Cet and chronomodulated triplet HAI in pts with unresectable and refractory LM-CRC. Methods: Rest-activity was monitored q1min using a wrist watch actigraph worn for three weeks, starting 1 week before HAI onset. A robust and validated parameter (I&lt;O), the relative measure of activity In-bed vs Out-of-bed, was used to evaluate rest-activity patterns. Tumor response was evaluated using RECIST criteria. Results: 10M and 3F, aged 33-72 y (median, 60 y) had a good Performance Status (0, 10 pts; 1, 3 pts) and received one (7 pts), two or three (6 pts) prior chemotherapy lines. Pts displayed complete or partial response (1 CR, 6 PR), or stable disease (SD, 6 pts). Median I&lt;0 was 95.4% (25-75% quartiles, 88.8-98.0) at baseline, 92.8% (89.4- 96.2) during the treatment week (p&lt;0.001 vs “baseline”) and 95.0% (89.2- 97.6, NS) on the week after HAI. On this last week, I&lt;O improved or recovered fully in 5 pts (38.5%), or partly in 3 pts (23.1%). Rest-activity rhythm disruption persisted in 5 pts (38.5%). An objective tumor response was achieved in 7/ 8 pts whose I&lt;O improved or recovered (87.5%) while the poor I&lt;O computed for 5 patients on the week after HAI predicted for SD only (p=0.003). This relation was independent of PS and prior chemotherapy lines (p=0.013). Conclusions: The robustness of the rest-activity rhythm during the first course of Chrono-Optiliv was an early signal that predicted subsequent antitumor activity. Further testing of this circadian biomarker is warranted as an early surrogate endpoint of antitumor efficacy of Chrono-Optiliv. Clinical trial information: NCT00852228.
Microbial aetiology of brain abscess in a UK cohort: Prominent role of Streptococcus intermedius
Authors: Christopher A Darlow, Nicholas McGlashan, Richard Kerr, Sarah Oakley, Pieter Pretorius, Nicola Jones, Philippa C Matthews
Journal: Journal of Infection (2020)

BackgroundBrain abscess is an uncommon condition, but carries high mortality. Current treatment guidelines are based on limited data. Surveillance of clinical, radiological and microbiology data is important to inform patient stratification, interventions, and antimicrobial stewardship.MethodsWe undertook a retrospective, observational study of patients with brain abscess, based on hospital coding, in a UK tertiary referral teaching hospital. We reviewed imaging data, laboratory microbiology, and antibiotic prescriptions.ResultsOver a 47 month period, we identified 47 adults with bacterial brain abscess (77% male, median age 47 years). Most of the abscesses were solitary frontal or parietal lesions. A microbiological diagnosis was secured in 39/47 (83%) of cases, among which the majority were of the Streptococcus milleri group (27/39; 69%), with a predominance of Streptococcus intermedius (19/27; 70%). Patients received a median of 6 weeks of intravenous antibiotics (most commonly ceftriaxone), with variable oral follow-on regimens. Ten patients (21%) died, up to 146 days after diagnosis. Mortality was significantly associated with increasing age, multiple abscesses, immunosuppression and the presence of an underlying cardiac anomaly.ConclusionOur data suggest that there has been a shift away from staphylococcal brain abscesses, towards S. intermedius as a dominant pathogen. In our setting, empiric current first line therapy with ceftriaxone remains appropriate on microbiological grounds and narrower spectrum therapy may sometimes be justified. Mortality of this condition remains high among patients with comorbidity. Prospective studies are required to inform optimum dose, route and duration of antimicrobial therapy.