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Ertapenem usage in cancer patients with and without neutropenia: a report on 97 cases from a comprehensive cancer center.

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Ertapenem usage in cancer patients with and without neutropenia: a report on 97 cases from a comprehensive cancer center.

Infection. 2015 May 1;

Authors: Nesher L, Tverdek FP, Mahajan SN, Chemaly RF, Rolston KV

Abstract
PURPOSE: Ertapenem is being increasingly utilized in cancer patients, but published data regarding its usage are limited. Our objective was to describe the various indications for ertapenem therapy and its safety and efficacy in cancer patients.
METHODS: We conducted a retrospective cohort study of cancer patients who received monotherapy with ertapenem for at least 72 h, between January 2007 and February 2013.
RESULTS: Among 97 unique patients who received ertapenem monotherapy, the most common indications were: (1) To facilitate discharge from the hospital of stable patients still requiring antimicrobial therapy (46 %). (2) Primary therapy of various documented infections (bacteremia, pneumonia, urinary tract infection, skin and skin structure infection) with ertapenem (28 %). (3) De-escalation from a different broad-spectrum agent or regimen to ertapenem within the hospital setting in patients not ready for discharge (25 %). The median age of the 97 patients studied was 59 years (range 9-87 years) with 52 % being men. Most patients had underlying hematologic malignancies (54 %), and 7 % were recipients of hematopoietic stem cell transplantation. Twenty-nine patients (30 %) were neutropenic, 26 % were diabetic, and 6 % had chronic lung disease. Primary ertapenem monotherapy was successful in all patients, de-escalation in 95.8 % of patients, and the strategy of discharge on outpatient therapy with ertapenem in 95.6 % of patients. Patients failing de-escalation or early discharge responded to alternative regimens. We documented no significant ertapenem associated toxicity or adverse events.
CONCLUSIONS: Ertapenem appears to be safe and effective for several indications in cancer patients.

PMID: 25929421 [PubMed – as supplied by publisher]

Further Modification of the Modified Hodge Test for Detecting Metallo-β-Lactamase-Producing Carbapenem-Resistant Enterobacteriaceae.

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Further Modification of the Modified Hodge Test for Detecting Metallo-β-Lactamase-Producing Carbapenem-Resistant Enterobacteriaceae.

Ann Lab Med. 2015 May;35(3):298-305

Authors: Kim HK, Park JS, Sung H, Kim MN

Abstract
BACKGROUND: The modified Hodge test (MHT) was designed to detect carbapenemase-producing Enterobacteriaceae (CPE). This study evaluated variables to improve the performance of MHT.
METHODS: Carbapenem-resistant Enterobacteriaceae isolated from November 2010 to March 2013 at the Asan Medical Center, were evaluated, including 33 metallo-β-lactamase (MBL) producers and 103 non-CPEs. MHT was performed by using two carbapenem disks (ertapenem and meropenem; Becton Dickinson, USA), three media (Mueller-Hinton agar (MHA), MacConkey agar (MAC), and zinc-enriched MHA), and two inoculums (0.5-McFarland [McF] suspension and a 10-fold dilution of it.) PCR was performed to detect β-lactamase genes of the MBL, AmpC, and CTX-M types.
RESULTS: The sensitivity of MHT for detecting New Delhi metallo-β-lactamase (NDM) producers was highest using ertapenem and 0.5-McF, 52.0% on MHA and 68.0% on MAC, respectively. NDM-producing Klebsiella pneumoniae (NDMKP) were detected with higher sensitivity on MAC (78.6%) vs. MHA (28.6%) (P=0.016), but VIM-producing Enterobacter, Citrobacter, and Serratia were detected with higher sensitivity on MHA (78.5%) vs. MAC (14.3%) (P=0.004). MBL producers were consistently identified with lower sensitivity using meropenem vs. ertapenem, 39.4% vs. 60.6% (P=0.0156), respectively. The effects of zinc and inoculum size were insignificant. Enterobacter aerogenes producing unspecified AmpC frequently demonstrated false positives, 66.7% with ertapenem and 22.2% with meropenem.
CONCLUSIONS: The MHT should be adjusted for the local distribution of species and the carbapenemase type of MBL producers. MAC and ertapenem are preferable for assessing NDMKP, but MHA is better for VIM. Laboratory physicians should be aware of the limited sensitivity of MHT and its relatively high false-positive rate.

PMID: 25932437 [PubMed – in process]

Cetuximab directly inhibits P-glycoprotein function in vitro independently of EGFR binding.

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Cetuximab directly inhibits P-glycoprotein function in vitro independently of EGFR binding.

Eur J Pharm Sci. 2015 Apr 27;

Authors: Chu C, Noël-Hudson MS, Bénard J, Ha-Duong T, Allaoui F, Farinotti R, Bonhomme-Faivre L

Abstract
PURPOSE: Cancer chemotherapy typically combines anticancer drugs from different mechanisms of action. However, cancer cells could become resistant to chemotherapy via P-gp or other ATP binding cassette proteins. The objective of this study was to evaluate whether cetuximab, monoclonal antibody directed towards epidermal growth factor receptor, could increase intracellular concentration of conventional chemotherapy by interacting with P-gp.
METHODS: Two human ovarian carcinoma (IGROV1) and two human embryonary kidney (HEK) cell lines, overexpressing or weakly expressing P-gp, were used. Their EGFR expressions were compared. Cetuximab effect on P-gp functionality was evaluated by measuring doxorubicin (P-gp fluorescent substrate) intracellular accumulation. Cetuximab ability to increase doxorubicin cytotoxicity was evaluated by MTT test. A quaternary structure model of the P-gp-Cetuximab complex was established.
RESULTS: Exposure of cetuximab in therapeutic concentrations range with doxorubicin led to significant doxorubicin accumulation and reversion of doxorubicin resistance in P-gp expressing cells lines. Molecular modeling of P-gp-cetuximab interactions showed that cetuximab is able to bind P-gp extracellular part.
CONCLUSIONS: Cetuximab increases a P-gp substrate intracellular accumulation in both P-gp expressing cell lines, independently of their EGFR expression. One hypothesis is that cetuximab binding on P-gp could hamper the conformational changes that occur during drugs efflux. Our results offer new possibilities of research on monoclonal antibodies influence in MDR phenomena.

PMID: 25930120 [PubMed – as supplied by publisher]

Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI).

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Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI).

Lancet. 2015 Apr 27;

Authors: Wagenlehner FM, Umeh O, Steenbergen J, Yuan G, Darouiche RO

Abstract
BACKGROUND: Treatment of complicated urinary-tract infections is challenging due to rising antimicrobial resistance. We assessed the efficacy and safety of ceftolozane-tazobactam, a novel antibacterial with Gram-negative activity, in the treatment of patients with complicated lower-urinary-tract infections or pyelonephritis.
METHODS: ASPECT-cUTI was a randomised, double-blind, double-dummy, non-inferiority trial done in 209 centres in 25 countries. Between July, 2011, and September, 2013, hospital inpatients aged 18 years or older who had pyuria and a diagnosis of a complicated lower-urinary-tract infection or pyelonephritis were randomly assigned in a 1:1 ratio to receive intravenous 1·5 g ceftolozane-tazobactam every 8 h or intravenous high-dose (750 mg) levofloxacin once daily for 7 days. The randomisation schedule was computer generated in blocks of four and stratified by study site. The next allocation was obtained by the study site pharmacist via an interactive voice-response system. The primary endpoint was a composite of microbiological eradication and clinical cure 5-9 days after treatment in the microbiological modified intention-to-treat (MITT) population, with a non-inferiority margin of 10%. This study is registered with ClinicalTrials.gov, numbers NCT01345929 and NCT01345955.
FINDINGS: Of 1083 patients enrolled, 800 (73·9%), of whom 656 (82·0%) had pyelonephritis, were included in the microbiological MITT population. Ceftolozane-tazobactam was non-inferior to levofloxacin for composite cure (306 [76·9%] of 398 vs 275 [68·4%] of 402, 95% CI 2·3-14·6) and, as the lower bound of the two-sided 95% CI around the treatment difference was positive and greater than zero, superiority was indicated. Adverse event profiles were similar in the two treatment groups and were mainly non-serious.
INTERPRETATION: Treatment with ceftolozane-tazobactam led to better responses than high-dose levofloxacin in patients with complicated lower-urinary-tract infections or pyelonephritis.
FUNDING: Cubist Pharmaceuticals.

PMID: 25931244 [PubMed – as supplied by publisher]

Use of alcohol vinegar in the inhibition of Candida spp. and its effect on the physical properties of acrylic resins.

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Use of alcohol vinegar in the inhibition of Candida spp. and its effect on the physical properties of acrylic resins.

BMC Oral Health. 2015 Apr 28;15(1):52

Authors: de Castro RD, Mota AC, de Oliveira Lima E, Batista AU, de Araújo Oliveira J, Cavalcanti AL

Abstract
BACKGROUND: Given the high prevalence of oral candidiasis and the restricted number of antifungal agents available to control infection, this study investigated the in vitro antifungal activity of alcohol vinegar on Candida spp. and its effect on the physical properties of acrylic resins.
METHODS: Tests to determine the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) of vinegar alcohol (0.04 g/ml of acetic acid) and nystatin (control) were performed. The antifungal activity of alcohol vinegar was assessed through microbial growth kinetic assays and inhibition of Candida albicans adhesion to acrylic resin at different intervals of time. Surface roughness and color of the acrylic resin were analyzed using a roughness meter and color analyzer device.
RESULTS: Alcohol vinegar showed MIC75% and MFC62.5% of 2.5 mg/ml, with fungicidal effect from 120 min, differing from nystatin (p < 0.0001), which showed fungistatic effect. Alcohol vinegar caused greater inhibition of C. albicans adhesion to the acrylic resin (p ≤ 0.001) compared to nystatin and did not change the roughness and color parameters of the material.
CONCLUSION: Alcohol vinegar showed antifungal properties against Candida strains and caused no physical changes to the acrylic resin.

PMID: 25928798 [PubMed – as supplied by publisher]

Antimicrobial susceptibility trends among Streptococcus pneumoniae over an 11-year period in an Iranian referral children Hospital.

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Antimicrobial susceptibility trends among Streptococcus pneumoniae over an 11-year period in an Iranian referral children Hospital.

Iran J Microbiol. 2014 Dec;6(6):382-6

Authors: Haghi Ashtiani MT, Sadeghian M, Nikmanesh B, Pourakbari B, Mahmoudi S, Mamishi S

Abstract
BACKGROUND AND OBJECTIVES: The appearance of antibiotic resistance in Streptococcus pneumoniae has raised a global concern over the past three decades. This study was conducted to determine the antimicrobial susceptibility of S. pneumoniae isolated from patients in Children´s Medical Center (CMC) Hospital during 2001 to 2011.
MATERIALS AND METHODS: During the 11 years period, a total of 194 S. pneumoniae isolates were collected in CMC Hospital. Antimicrobial susceptibility testing was performed by the Kirby-Bauer disk diffusion method and time-series analysis was used to evaluate the antimicrobial susceptibility changes over the time.
RESULTS AND CONCLUSION: Antimicrobial susceptibility of S. pneumoniae to different antibiotics decreased from 2001 to 2011 as: penicillin from 78% to 32%, erythromycin from 75% to 35%, chloramphenicol from 94% to 55%, ampicillin from 70% to 62%, ceftriaxone from 100% to 87%, sulfametoxazole from 57% to 40%. We did not find any significant difference between the susceptibility of isolates from sterile and non-sterile sources. It would be an important key to consider antimicrobial stewardship as an essential factor to prevent the development of antimicrobial resistance.

PMID: 25926954 [PubMed]