Synergistic Activity of Colistin plus Rifampin against Colistin-Resistant KPC-producing Klebsiella pneumoniae.

Synergistic Activity of Colistin plus Rifampin against Colistin-Resistant KPC-producing Klebsiella pneumoniae.

Antimicrob Agents Chemother. 2013 Jun 10;

Authors: Tascini C, Tagliaferri E, Giani T, Leonildi A, Flammini S, Casini B, Lewis R, Ferranti S, Rossolini GM, Menichetti F

Abstract
Infections caused by carbapenem-resistant KPC-producing Klebsiella pneumoniae are responsible for high mortality and represent a major therapeutic challenge especially when the isolates are also resistant to colistin. We used the checkerboard method to evaluate the synergistic activity of 10 antibiotic combinations against 13 colistin-resistant KPC K. pneumoniae (colistin MIC range: 8-128 mg/l). Colistin plus rifampin was the only combination that demonstrated consistent synergistic bacteriostatic activity against 13/13 strains tested, reducing the colistin MIC below the susceptibility breakpoint (MIC ≤ 2 mg/l) in 7/13 strains at rifampin concentrations ranging from 4 to 16 mg/l. Bactericidal synergistic activity was also documented for 8/13 tested strains. Other antimicrobial combinations with carbapenems, gentamicin and tigecycline showed variable synergistic results. Colistin plus rifampin also exhibited bacteriostatic synergistic activity against 4/4 colistin-susceptible KPC K. pneumoniae (colistin MIC range: 0.5-2 mg/l), and 4/4 ertapenem-resistant, ESBL producing K. pneumoniae (ertapenem MIC range: 16-32 mg/l). Collectively, our data suggest that colistin plus rifampin is the most consistently synergistic combination against KPC-producing K. pneumoniae, including colistin-resistant strains. Colistin-rifampin combinations may have a role in the treatment of multidrug-resistant K. pneumoniae, and possibility slow the selection of hetero-resistant subpopulations during colistin therapy.

PMID: 23752510 [PubMed – as supplied by publisher]

The significance of serum urokinase plasminogen activation receptor (suPAR) in the diagnosis and follow-up of febrile neutropenic patients with hematologic malignancies.

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The significance of serum urokinase plasminogen activation receptor (suPAR) in the diagnosis and follow-up of febrile neutropenic patients with hematologic malignancies.

Int J Infect Dis. 2013 Jun 3;

Authors: Kaya S, Köksal I, Menteşe A, Sönmez M, Sümer A, Yıldırım SS, Yılmaz G

Abstract
OBJECTIVES: The purpose of this study was to investigate serum levels of serum urokinase plasminogen activation receptor (suPAR) during the first week of febrile neutropenia and to demonstrate the significance of this biomarker in the diagnosis and follow-up of febrile neutropenic patients with hematologic malignancies. METHODS: The study was performed between January 2011 and January 2012 at Karadeniz Technical University, Turkey. For neutropenic patients with hematologic malignancies, the day before the onset of fever and the first day of the febrile neutropenia attack were taken as days 0 and 1, respectively. Blood samples were obtained from patients with hematologic malignancies on days 0, 1, 3, 5, and 7. Sixty-eight healthy volunteers were enrolled as the control group. suPAR levels were determined using an ELISA kit following the manufacturer’s protocols. Twenty-six male and 14 female patients with hematologic malignancies, the majority with acute/myeloid/lymphocytic leukemia, aged 19-78 years (mean 46.8 years), were included. Fifty febrile neutropenic attacks were investigated in these patients. RESULTS: The mean serum levels of the controls and suPAR 0 were 3.9±1.5ng/ml and 5.8±2.7ng/ml, respectively. Serum levels of suPAR rose earlier than levels of C-reactive protein and procalcitonin. Serum suPAR levels increased in patients with hematologic malignancies and were found to represent an important serum biomarker for the early prediction of neutropenic fever. A decrease in serum suPAR levels was found to be correlated with treatment response due to antibiotics in this patient group. There were significant differences in suPAR 1 levels between patients with documented infection and those with fever of unknown origin in favor of the former. When the suPAR 1 results were analyzed using the receiver operating characteristics (ROC) curve method, the optimum diagnostic cut-off point was 5.87 ng/ml, the area underneath the ROC curve (AUC) was 0.81 (95% confidence interval 0.68-0.91), sensitivity was 100%, specificity was 69%, negative predictive value (NPV) was 100%, and positive predictive value (PPV) was 70%. CONCLUSIONS: We conclude that suPAR is an important biomarker that can predict infections in the early stage of febrile neutropenia with high sensitivity and NPV for patients with hematologic malignancies. It is also advantageous since it shows the response to treatment with antibiotherapy in the early stage.

PMID: 23742830 [PubMed – as supplied by publisher]

A ten-year surveillance for antimicrobial susceptibility of Escherichia coli and Klebsiella pneumoniae in community- and hospital-associated intra-abdominal infections in China.

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A ten-year surveillance for antimicrobial susceptibility of Escherichia coli and Klebsiella pneumoniae in community- and hospital-associated intra-abdominal infections in China.
J Med Microbiol. 2013 Jun 5;
Au…

In Vitro Activity of Isavuconazole and Comparator Antifungal Agents Tested Against a Global Collection of Opportunistic Yeasts and Moulds.

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In Vitro Activity of Isavuconazole and Comparator Antifungal Agents Tested Against a Global Collection of Opportunistic Yeasts and Moulds.

J Clin Microbiol. 2013 Jun 5;

Authors: Pfaller MA, Messer SA, Rhomberg PR, Jones RN, Castanheira M

Abstract
BACKGROUND: Isavuconazole is a new broad-spectrum triazole with a favorable pharmacokinetic and safety profile.METHODS: We report the MIC distributions for isavuconazole and 111 isolates of Candida (C. albicans [42 isolates], C. glabrata (25), C. parapsilosis (22), C. tropicalis (14), and C. krusei (8)) as determined by both CLSI and EUCAST broth microdilution (BMD) methods; also the comparative activity of isavuconazole, itraconazole, fluconazole, posaconazole, voriconazole and the three echinocandins was assessed against a recent (2011) global collection of 1,358 isolates of Candida spp., 101 of Aspergillus spp., 54 of non-Candida yeasts, and 21 of non-Aspergillus moulds as determined by CLSI BMD methods.RESULTS: The overall essential agreement (EA; ± two log2 dilutions) between the CLSI and EUCAST methods was 99.1% (EA ± 1 log 2 dilution, 90.1% [range 80.0-100.0%]). The activity of isavuconazole against the larger collection of Candida spp. and Aspergillus spp. was comparable to that of posaconazole and voriconazole: MIC90 values for these 3 triazoles against Candida spp. was 0.5, 1 and 0.25 μg/ml, respectively and against Aspergillus spp. was 2, 1 and 1 μg/ml, respectively. Isavuconazole showed good activity against Cryptococcus neoformans (MIC90, 0.12 μg/ml) and other non-Candida yeasts (MIC90, 1 μg/ml), but was less potent against non-Aspergillus moulds (MIC90, >8 μg/ml). MIC values for isavuconazole and three mucormycetes isolates were 4, 1 and 2 μg/ml, respectively, whereas all three were inhibited by 1 μg/ml of posaconazole.CONCLUSIONS: Isavuconazole demonstrates broad-spectrum activity against this global collection of opportunistic fungi and both CLSI and EUCAST methods may be used to test this agent against Candida with highly comparable results.

PMID: 23740727 [PubMed – as supplied by publisher]

Public response to an anthrax attack: a multiethnic perspective.

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Public response to an anthrax attack: a multiethnic perspective.

Biosecur Bioterror. 2012 Dec;10(4):401-11

Authors: Steelfisher GK, Blendon RJ, Brulé AS, Ben-Porath EN, Ross LJ, Atkins BM

Abstract
The 2001 anthrax attacks emphasized the need to develop outreach that would more effectively support racial/ethnic minority populations during a bioterrorism incident. Given the importance of antibiotic prophylaxis in a future anthrax attack, it should be a priority to better support racial/ethnic minorities in mass dispensing programs. To examine the needs and perspectives of racial/ethnic minorities, this study used a nationally representative poll of 1,852 adults, including 1,240 whites, 261 African Americans, and 282 Hispanics. The poll examined public reactions to a »worst-case scenario» in which cases of inhalation anthrax are discovered without an identified source and the entire population of a city or town is asked to receive antibiotic prophylaxis within 48 hours. Findings suggest willingness across all racial/ethnic groups to comply with recommendations to seek prophylaxis at dispensing sites. However, findings also indicate possible barriers for racial/ethnic minorities, including greater concern about pill safety and multiple attacks as well as lesser knowledge about inhalation anthrax. Across all racial/ethnic groups, roughly half would prefer to receive antibiotics at mass dispensing sites rather than through the US Postal Service. People in racial/ethnic minority groups were more likely to say this preference stems from a desire to speak with staff or to exchange medication formulation or type. Findings suggest the need for tailored outreach to racial/ethnic minorities through, for example, emphasis on key messages and enhanced understandability in communications, increased staff for answering questions in relevant dispensing sites, and long-term trust building with racial/ethnic minority communities.

PMID: 23244501 [PubMed – indexed for MEDLINE]

Impact of an enhanced antibiotic stewardship on reducing methicillin-resistant Staphylococcus aureus in primary and secondary healthcare settings.

Impact of an enhanced antibiotic stewardship on reducing methicillin-resistant Staphylococcus aureus in primary and secondary healthcare settings.

Epidemiol Infect. 2013 Jun 5;:1-7

Authors: Aldeyab MA, Scott MG, Kearney MP, Alahmadi YM, Magee FA, Conlon G, McElnay JC

Abstract
SUMMARY The objective of this study was to evaluate the impact of restricting high-risk antibiotics on methicillin-resistant Staphylococcus aureus (MRSA) incidence rates in a hospital setting. A secondary objective was to assess the impact of reducing fluoroquinolone use in the primary-care setting on MRSA incidence in the community. This was an interventional, retrospective, ecological investigation in both hospital and community (January 2006 to June 2010). Segmented regression analysis of interrupted time-series was employed to evaluate the intervention. The restriction of high-risk antibiotics was associated with a significant change in hospital MRSA incidence trend (coefficient = -0·00561, P = 0·0057). Analysis showed that the intervention relating to reducing fluoroquinolone use in the community was associated with a significant trend change in MRSA incidence in community (coefficient = -0·00004, P = 0·0299). The reduction in high-risk antibiotic use and fluoroquinolone use contributed to both a reduction in incidence rates of MRSA in hospital and community (primary-care) settings.

PMID: 23735079 [PubMed – as supplied by publisher]

Antibiotic Consumption and Healthcare-Associated Infections Caused by Multidrug-Resistant Gram-Negative Bacilli at a Large Medical Center in Taiwan from 2002 to 2009: Implicating the Importance of Antibiotic Stewardship.

Antibiotic Consumption and Healthcare-Associated Infections Caused by Multidrug-Resistant Gram-Negative Bacilli at a Large Medical Center in Taiwan from 2002 to 2009: Implicating the Importance of Antibiotic Stewardship.

PLoS One. 2013;8(5):e65621

Authors: Chen IL, Lee CH, Su LH, Tang YF, Chang SJ, Liu JW

Abstract
BACKGROUND: Better depicting the relationship between antibiotic consumption and evolutionary healthcare-associated infections (HAIs) caused by multidrug-resistant Gram-negative bacilli (MDR-GNB) may help highlight the importance of antibiotic stewardship.
METHODOLOGYPRINCIPAL FINDINGS: The correlations between antibiotic consumption and MDR-GNB HAIs at a 2,700-bed primary care and tertiary referral center in Taiwan between 2002 and 2009 were assessed. MDR-GNB HAI referred to a HAI caused by MDR-Enterobacteriaceae, MDR-Pseudomonas aeruginosa or MDR-Acinetobacter spp. Consumptions of individual antibiotics and MDR-GNB HAI series were first evaluated for trend over time. When a trend was significant, the presence or absence of associations between the selected clinically meaningful antibiotic resistance and antibiotic consumption was further explored using cross-correlation analyses. Significant major findings included (i) increased consumptions of extended-spectrum cephalosporins, carbapenems, aminopenicillins/β-lactamase inhibitors, piperacillin/tazobactam, and fluoroquinolones, (ii) decreased consumptions of non-extended-spectrum cephalosporins, natural penicillins, aminopenicillins, ureidopenicillin and aminoglycosides, and (iii) decreasing trend in the incidence of the overall HAIs, stable trends in GNB HAIs and MDR-GNB HAIs throughout the study period, and increasing trend in HAIs caused by carbapenem-resistant (CR) Acinetobacter spp. since 2006. HAIs due to CR-Acinetobacter spp. was found to positively correlate with the consumptions of carbapenems, extended-spectrum cephalosporins, aminopenicillins/β-lactamase inhibitors, piperacillin/tazobactam and fluoroquinolones, and negatively correlate with the consumptions of non-extended-spectrum cephalosporins, penicillins and aminoglycosides. No significant association was found between the increased use of piperacilllin/tazobactam and increasing HAIs due to CR-Acinetobacter spp.
CONCLUSIONS: The trend in overall HAIs decreased and trends in GNB HAIs and MDR-GNB HAIs remained stable over time suggesting that the infection control practice was effective during the study period, and the escalating HAIs due to CR- Acinetobacter spp. were driven by consumptions of broad-spectrum antibiotics other than piperacillin/tazobactam. Our data underscore the importance of antibiotic stewardship in the improvement of the trend of HAIs caused by Acinetobacter spp.

PMID: 23738018 [PubMed – as supplied by publisher]

Economic evaluation of posaconazole versus standard azole therapy as prophylaxis against invasive fungal infections in patients with prolonged neutropenia in Canada.

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Economic evaluation of posaconazole versus standard azole therapy as prophylaxis against invasive fungal infections in patients with prolonged neutropenia in Canada.
Can J Infect Dis Med Microbiol. 2012;23(2):59-64