In Vivo Efficacy of the Novel Aminoglycoside ACHN-490 in Murine Infection Models

Size: px
Start display at page:

Download "In Vivo Efficacy of the Novel Aminoglycoside ACHN-490 in Murine Infection Models"

Transcription

1 ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Apr. 2011, p Vol. 55, No /11/$12.00 doi: /aac Copyright 2011, American Society for Microbiology. All Rights Reserved. In Vivo Efficacy of the Novel Aminoglycoside ACHN-490 in Murine Infection Models Noe Reyes, James B. Aggen, Corwin F. Kostrub* Achaogen, Inc., 7000 Shoreline Court, Suite 371, South San Francisco, California Received 23 June 2010/Returned for modification 10 August 2010/Accepted 24 January 2011 Aminoglycosides are broad-spectrum antibiotics with particular clinical utility against life-threatening infections. As resistance to antibiotics, including aminoglycosides, continues to grow, there is a need for new and effective antimicrobial agents. ACHN-490 is a novel aminoglycoside in clinical development with activity against multidrugresistant Gram-negative and select Gram-positive pathogens. Here we assess the in vivo efficacy of ACHN-490 against a variety of common pathogens in two murine models: the septicemia and neutropenic thigh models. When its activity against a gentamicin-susceptible strain of Escherichia coli was tested in the septicemia model, ACHN-490 improved 7-day survival with a dose-response profile similar to that of gentamicin, with 100% survival seen at doses of 1.6 mg/kg of body weight and above. In animals infected with a gentamicin-susceptible strain of Pseudomonas aeruginosa, treatment with either ACHN-490 or gentamicin led to 100% survival at doses of 16 mg/kg and above in the septicemia model. ACHN-490 was also effective in the neutropenic thigh model, reducing multidrug-resistant Enterobacteriaceae family and methicillin-resistant Staphylococcus aureus strains, as well as broadly susceptible strains, to static levels with dose-dependent activity. Against gentamicin-sensitive Enterobacteriaceae and methicillinresistant S. aureus, the efficacy of ACHN-490 was comparable to that of gentamicin. However, gentamicin-resistant Enterobacteriaceae strains and those harboring the Klebsiella pneumoniae carbapenemase responded to ACHN-490 but not gentamicin, with static doses ranging from 12 mg/kg to 64 mg/kg for ACHN-490. These results suggest that ACHN-490 has the potential to become a clinically useful agent against drug-resistant pathogens, including Enterobacteriaceae, P. aeruginosa, and methicillin-resistant S. aureus, and support further development of this promising novel aminoglycoside. * Corresponding author. Mailing address: Achaogen, Inc., 7000 Shoreline Court, Suite 371, South San Francisco, CA Phone: (650) Fax: (650) ckostrub@achaogen.com. Published ahead of print on 31 January As antibiotic use has increased over the last half century, so has the ability of bacteria to evade the activity of antibiotics. Reports that penicillin use in humans resulted in the emergence of penicillin-resistant Staphylococcus aureus were already appearing in the medical literature in 1945, only 1 year after commercial production of penicillin began (28). Although the introduction of other classes of antibiotics has helped alleviate the problem, antibacterial resistance continues to grow rapidly as bacteria develop new mechanisms to render antibiotics ineffective and existing mechanisms of resistance spread. A novel antibiotic class active against Gram-negative bacteria has not been introduced for almost 50 years. This has led to an escalating need for new antibiotics; indeed, the Infectious Diseases Society of America has developed the Initiative to encourage the introduction of at least 10 new, safe, and effective antibacterial drugs by the year 2020 (13). The first aminoglycoside, streptomycin, was introduced almost 70 years ago (16, 25). Aminoglycosides have broad-spectrum activity and have historically been useful in serious, lifethreatening infections (3). As with other classes of antibiotics, many mechanisms of resistance to aminoglycosides have developed in once-susceptible pathogens. These primarily consist of the aminoglycoside-modifying enzymes (AMEs) N-acetyltransferases, AAC (N-acetylation), O-nucleotidyltransferases, ANT (O-adenylylation), O-phosphotransferases, and APH (Ophosphorylation) (15), which inactivate aminoglycosides by covalently modifying specific amino or hydroxyl moieties on the drugs. Because aminoglycosides are hydrophilic and thus require transport across cell membranes, bacteria that develop mechanisms to affect this process can also be resistant to aminoglycosides. Such mechanisms include the upregulation of efflux pumps and reductions in membrane permeability. Recently, methyltransferases that modify bacterial rrna, the molecular target of aminoglycosides, and that confer high-level resistance to all widely used aminoglycosides have been shown to occur at a low incidence in clinical isolates (8). ACHN-490 (Fig. 1) is a novel aminoglycoside in development by Achaogen, Inc. (South San Francisco, CA). ACHN- 490 is derived from sisomicin in an 8-step process by which 2 of its amino groups are modified to maintain strong antibacterial potency and broad-spectrum activity while blocking modification by bacterial AMEs that confer resistance to other aminoglycosides. We showed previously that ACHN-490 is active in vitro against Gram-negative and Gram-positive pathogens and has potent activity against gentamicin-susceptible and -resistant bacteria (1). Members of the Enterobacteriaceae family and Acinetobacter, Pseudomonas, and Staphylococcus strains having a wide variety of single or multiple aminoglycoside resistance mechanisms were inhibited by ACHN-490 in vitro. Here we assess whether the in vitro activity of ACHN-490 translates to activity in vivo in murine infection models. MATERIALS AND METHODS ACHN-490 was provided by Achaogen, Inc. All aspects of this work, including housing, experimentation, and disposal of animals, were performed in accordance with the Guide for the Care and Use of Laboratory Animals (14). Animal manipulations and CFU determinations for the in vivo infection models were 1728

2 VOL. 55, 2011 IN VIVO EFFICACY OF NOVEL AMINOGLYCOSIDE ACHN FIG. 1. Structure of ACHN-490. carried out at the contract research organization MDS Pharma Services (now Ricerca; Taipei, Taiwan), and all mice were obtained from Charles River Laboratories (Wilmington, MA). Achaogen provided non-american Type Culture Collection (ATCC) bacterial strains and determined all MICs using the broth microdilution method recommended by the Clinical and Laboratory Standards Institute (5). The MICs of ACHN-490 and comparator antibiotics against the bacterial strains used are presented in Table 1. Septicemia model. CD-1 strain-derived male mice weighing 24 2 g were inoculated with Escherichia coli ATCC or Pseudomonas aeruginosa ATCC Twofold the 90 to 100% lethal dose (LD ; total inocula given, CFU/mouse for E. coli and CFU/mouse for P. aeruginosa) in 0.5 ml brain heart infusion broth containing 5% mucin was injected intraperitoneally to produce septicemia. At 1 h postinoculation, antibiotic or vehicle alone was administered by subcutaneous injection. Each treatment or control group had 10 mice. Mortality was recorded daily for 7 days postinfection. Nonlinear regression (GraphPad Prism software) was used to determine the 50% effective dose (ED 50 ) for each antibiotic from its dose-response. Neutropenic thigh model. Specific pathogen-free male CD-1 mice (6 mice per dosing group) weighing 24 2 g were rendered neutropenic with 2 intraperitoneal injections of cyclophosphamide (150 mg/kg of body weight 4 days prior to bacterial inoculation and 100 mg/kg 1 day before inoculation) (31). Bacteria were injected into the right thigh of each mouse at time zero. Inocula were selected on the basis of pilot studies with vehicle-treated animals that determined the maximum number of CFU that could be inoculated without substantial mortality during the course of the experiment. Aminoglycoside-susceptible Enterobacteriaceae strains included Klebsiella pneumoniae ATCC ( CFU/ mouse) and E. coli ATCC ( CFU/mouse). Multidrug-resistant (MDR) strains included K. pneumoniae AKPN1073 ( CFU/mouse) and E. coli AECO1003 ( CFU/mouse). Two strains expressing K. pneumoniae carbapenemase (KPC) were tested: K. pneumoniae AKPN1109 ( CFU/mouse) and Serratia marcescens ASMA1030 ( CFU/mouse). In addition, the model was also tested with a strain of methicillin-resistant S. aureus (MRSA; ATCC 33591; CFU/mouse). In vitro susceptibilities of the studied strains are presented in Table 1. The antibiotic or vehicle alone was administered twice by subcutaneous injection at 2 and 14 h postinoculation. Doses are reported as total dose (mg/kg/day). To assess in vivo antibiotic efficacy, the infected thighs were removed, weighed, FIG. 2. Efficacy of ACHN-490 and comparator aminoglycosides in septicemia model. and homogenized with a ceramic mortar in 3 to 4 ml of phosphate-buffered saline (ph 7.4). This homogenate was serially diluted, plated on Mueller-Hinton broth (BD Biosciences, San Jose, CA) with 1.5% Bacto agar (BD Biosciences), and then quantified. The mean log number of CFU/g thigh at 26 h postinfection (24 h after the first antibiotic dose) was compared to the mean log number of CFU/g thigh for untreated mice assessed at 2 h postinfection (static level). Static doses were estimated using nonlinear parametric curve fitting (GraphPad Prism software). RESULTS Experimental septicemia. Figure 2 shows the survival of mice with experimental septicemia. ACHN-490 demonstrated dose-dependent effects on survival in this model against both E. coli ATCC and P. aeruginosa ATCC 27853, with TABLE 1. In vitro activities of ACHN-490 and comparator antibiotics against strains used in in vivo efficacy studies Organism Phenotype Strain no. MIC (mg/liter) a ACHN-490 AMK ARB CIP GEN IMP VAN Escherichia coli Susceptible ATCC ND MDR AECO ND Klebsiella pneumoniae Susceptible ATCC ND ND MDR AKPN ND KPC AKPN ND ND ND Pseudomonas aeruginosa Susceptible ATCC ND Serratia marcescens KPC ASMA ND ND ND Staphylococcus aureus Methicillin resistant ATCC a AMK, amikacin; ARB, arbekacin; CIP, ciprofloxacin; GEN, gentamicin; IMP, imipenem; VAN, vancomycin; ND, not determined.

3 1730 REYES ET AL. ANTIMICROB. AGENTS CHEMOTHER. TABLE 2. Summary of estimated static doses of tested compounds in the mouse neutropenic thigh model Compound Estimated static dose (mg/kg/day) ATCC AECO1003 ATCC AKPN1073 AKPN1109 ASMA1030 ATCC ACHN Gentamicin Imipenem ND a Ciprofloxacin ND Arbekacin ND ND ND ND ND ND 148 Daptomycin ND ND ND ND ND ND 4 Vancomycin ND ND ND ND ND ND 20 a ND, not determined. 100% survival over 7 days achieved in mice given the highest doses. Mice injected with vehicle alone showed 100% mortality in this model within 48 h postinfection. Treatment with ACHN-490 led to the survival of mice infected with E. coli ATCC 25922, with an ED 50 of 0.6 mg/kg (95% confidence interval [CI] 0.5 to 0.8 mg/kg), compared to ED 50 sof0.7 mg/kg (95% CI 0.5 to 0.9 mg/kg) for gentamicin and 2.5 mg/kg (95% CI 1.9 to 3.1 mg/kg) for amikacin. Septicemia caused by P. aeruginosa ATCC led to 100% mortality within 72 h in mice treated with vehicle alone. Amikacin increased survival up to 80% at the highest dose tested, with a calculated ED 50 of 22.4 mg/kg (95% CI 15 to 39 mg/kg). ACHN-490 (ED mg/kg [95% CI 5.4 to 15 mg/kg]) and gentamicin (ED mg/kg [95% CI 3.9 to 7.1 mg/kg]) were more effective against P. aeruginosa than amikacin, achieving 100% survival and lower ED 50 s. Neutropenic thigh model. Results for all compounds and strains tested in the mouse neutropenic thigh model are summarized in Table 2. ACHN-490 demonstrated dose-dependent efficacy in the neutropenic thigh model against the aminoglycoside-susceptible Enterobacteriaceae isolates, K. pneumoniae ATCC 43816, and E. coli ATCC (Fig. 3a and c). ACHN- 490 doses of 16 or 64 mg/kg/day were sufficient to reduce the bacterial load to below the static level for both strains. The efficacy of ACHN-490 (static dose 7.8 mg/kg/day for K. pneumoniae ATCC 43816, static dose 10.6 mg/kg/day for E. coli ATCC 25922) was comparable to that of gentamicin and ciprofloxacin against these strains, whereas treatment with imipenem using the same dosing regimen was less effective against K. pneumoniae ATCC (static dose 200 mg/kg/day). ACHN-490 was also efficacious against MDR Enterobacteriaceae, including K. pneumoniae AKPN1073 (static dose 12 mg/kg/day) and E. coli AECO1003 (static dose 25 mg/kg/ day) (Fig. 3b and d). Against both organisms, ACHN-490 at 16 mg/kg/day reduced the bacterial load to near or slightly below the static level, while 64 mg/kg/day reduced the bacterial load to approximately 1 log below the static level. Gentamicin, on the other hand, was completely ineffective against K. pneumoniae AKPN1073; doses as high as 64 mg/kg/day failed to reduce the bacterial load relative to that in untreated animals. Likewise, gentamicin at doses of up to 64 mg/kg/day did not impede the growth of E. coli AECO1003. The highest dose of imipenem led to a bacterial load at or below the static level for both MDR strains tested. Two KPC-positive ( -lactam-resistant) strains were tested, and imipenem was ineffective against these strains, as expected (Fig. 3e and f). Likewise, gentamicin and ciprofloxacin did not inhibit either strain (static dose 64 mg/kg/day), an expected finding, since these strains also harbor AMEs and mutations in the quinolone resistance-determining region. ACHN-490, on the other hand, reduced the K. pneumoniae AKPN1109 bacterial load by 2 logs at the lowest dosage and by 3 logs at the highest dosage relative to those in tissues from untreated animals at 26 h postinfection (static dose 64 mg/kg/day). Against S. marcescens ASMA1030, the highest dose of ACHN- 490 reduced the bacterial load to below the static level (calculated static dose 37 mg/kg/day). ACHN-490 showed efficacy comparable to that of gentamicin in thighs infected with S. aureus ATCC (calculated static doses 54 mg/kg/day for ACHN-490 and 52 mg/kg/day for gentamicin; Fig. 4). For ACHN-490, 64 mg/kg/day reduced the bacterial load to the static level, while a dose of 256 mg/ kg/day reduced the bacterial load 2 logs below the static level, equal to the effect of the same dose of gentamicin and equal to the effect of treatment with daptomycin at 64 mg/kg/day. DISCUSSION The novel aminoglycoside ACHN-490 showed in vivo activity against common pathogens in two different standard infection models: experimental septicemia and the neutropenic thigh model. Bacterial strains against which ACHN-490 was active included P. aeruginosa, aminoglycoside-susceptible, carbapenemase-positive, and MDR strains of the Enterobacteriaceae, as well as MRSA. The in vivo efficacy of ACHN-490 was comparable to or better than that of legacy aminoglycosides in all cases, particularly in strains known to be aminoglycoside resistant (Tables 3 and 4). Against aminoglycoside-susceptible strains, for which the MICs were similar, the efficacy of ACHN-490 in the present study is as good as the efficacy shown TABLE 3. Relationship between in vitro activity and in vivo efficacy for ACHN-490 and gentamicin in the mouse septicemia model Organism a Strain no. Gentamicin ED 50 (mg/kg) ED 50 / MIC ACHN-490 ED 50 (mg/kg) ED 50 / MIC Escherichia coli ATCC ( ) b ( ) 0.6 Pseudomonas ATCC ( ) (5.4 15) 4.2 aeruginosa a Both isolates had the gentamicin-susceptible phenotype. b Values in parentheses are 95% CIs.

4 VOL. 55, 2011 IN VIVO EFFICACY OF NOVEL AMINOGLYCOSIDE ACHN Downloaded from FIG. 3. Efficacy of ACHN-490 and comparator antibiotics against Enterobacteriaceae in neutropenic thigh model. by legacy aminoglycosides in comparable models (7, 11, 19, 20). In addition, these results confirm the results obtained in earlier experiments, in which ACHN-490 demonstrated potent in vitro activity against a wide variety of Gram-negative organisms and MRSA (1). As with all animal models, the results presented here do not ensure efficacy of ACHN-490 in clinical use, but the demonstration of efficacy, in particular against highly resistant clinical isolates, by ACHN-490 in these mouse infection models illustrates the potential utility of this novel aminoglycoside against serious infections (6). The mouse septicemia model and neutropenic thigh model presented here are broadly utilized and accepted to be reasonable models to measure the efficacy of antibiotics nonclinically against systemic infections (10, 12). The efficacy of ACHN-490 in these models is encouraging and supports the ongoing clinical evaluation of ACHN-490 injec- FIG. 4. Efficacy of ACHN-490 and comparator antibiotics against S. aureus in neutropenic thigh model. on December 15, 2018 by guest

5 1732 REYES ET AL. ANTIMICROB. AGENTS CHEMOTHER. TABLE 4. Relationship between in vitro activity and in vivo efficacy for ACHN-490 and gentamicin in the mouse neutropenic thigh model Organism Phenotype Strain no. Gentamicin Static dose (mg/kg) Static dose/mic ACHN-490 Static dose (mg/kg) Static dose/mic Escherichia coli Susceptible ATCC (5.9 14) a (8.5 13) 11 MDR AECO NA b 25 (18 34) 25 Klebsiella pneumoniae Susceptible ATCC (13 17) ( ) 16 MDR AKPN NA 12 (8.4 16) 24 KPC AKPN NA 64 (23 130) 110 Serratia marcescens KPC ASMA NA 37 (31 44) 37 Staphylococcus aureus Methicillin resistant ATCC (41 67) (44 56) 14 a Values in parentheses are 95% CIs. b NA, not applicable. tion for efficacy and safety in humans. In recent phase 1 trials with healthy volunteers, ACHN-490 injection was well tolerated at doses up to 15 mg/kg/day for 5 days, with no signs of nephrotoxicity, ototoxicity, or other drug-related serious adverse events. The need for new antibiotics to combat antibacterial-resistant microbes is clear, given recent trends in the rates of resistance to broad-spectrum antibiotics. In the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program, between 9% and 13% of isolated E. coli, K. pneumoniae, and other Enterobacteriaceae isolates were resistant to tobramycin in 2008, with even greater rates of resistance to fluoroquinolones (between 13% and 32%) observed in the same isolates (24). Higher levels of resistance have been observed in other areas within Europe, Asia, and South America (22, 27, 29). In comparison, rates of resistance among all Enterobacteriaceae isolates collected in 2003 were 3.1% for tobramycin and between 7% and 9% for the fluoroquinolones, meaning that observed levels of resistance more than doubled in those 5 years. The emergence and spread of the newly recognized carbapenem-resistant Enterobacteriaceae have added further urgency to the situation, given that carbapenem antibiotics have been the last resort for treating infections caused by MDR Enterobacteriaceae (4, 26, 30). Infections caused by carbapenem-resistant K. pneumoniae have a particularly grim prognosis (23). Because many of the genes underlying carbapenem resistance are found on plasmids that carry additional resistance factors, extensively drug-resistant Enterobacteriaceae are likely to become more common as these plasmids spread. In the studies reported here, ACHN-490 demonstrated efficacy against MDR Enterobacteriaceae, including those harboring KPC, suggesting that this compound may have utility as empirical therapy for serious infections. Inadequate empirical treatment can have catastrophic consequences for patients infected with an unexpected or resistant bacterial strain. In hospital-acquired pneumonia or ventilatorassociated pneumonia, inadequate empirical treatment is associated with high costs, morbidity, and mortality (2, 9, 17, 18). In one study of adult trauma patients who experienced more than one ventilator-associated pneumonia episode for which inadequate empirical treatment was received, almost half of patients died (21). Clearly, the emergence and continued spread of antibiotic resistance require the introduction of new broad-spectrum antimicrobials that can improve outcomes, reduce the economic and medical burdens of MDR strains, and limit further development of resistance. Here we have shown that the novel aminoglycoside ACHN-490 demonstrates potent in vivo efficacy against a variety of drug-resistant and -susceptible pathogens in two different murine models. These promising results support the further evaluation of the safety and efficacy of this compound in clinical studies. ACKNOWLEDGMENTS All authors are employees of Achaogen, Inc., and satisfy the criteria for authorship defined by the International Committee of Medical Journal Editors. We thank MDS Pharma Services for expert technical assistance. Melanie Watson at AlphaBioCom, LLC, provided editorial assistance that was paid for by Achaogen, Inc. REFERENCES 1. Aggen, J. B., et al Synthesis and spectrum of the neoglycoside ACHN Antimicrob. Agents Chemother. 54: Alvarez-Lerma, F Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit. ICU-Acquired Pneumonia Study Group. Intensive Care Med. 22: Black, J., B. Calesnick, D. Williams, and M. J. Weinstein Pharmacology of gentamicin, a new broad-spectrum antibiotic, p Antimicrob. Agents Chemother Bratu, S., et al Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: a new threat to our antibiotic armamentarium. Arch. Intern. Med. 165: Clinical and Laboratory Standards Institute Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 7th ed. Clinical and Laboratory Standards Institute document M7-A7. Clinical and Laboratory Standards Institute, Wayne, PA. 6. Craig, W Relevance of animal models for clinical treatment. Eur. J. Clin. Microbiol. Infect. Dis. 12(Suppl. 1):S55 S Craig, W. A., J. Redington, and S. C. Ebert Pharmacodynamics of amikacin in vitro and in mouse thigh and lung infections. J. Antimicrob. Chemother. 27(Suppl. C): Doi, Y., and Y. Arakawa S ribosomal RNA methylation: emerging resistance mechanism against aminoglycosides. Clin. Infect. Dis. 45: Dupont, H., H. Mentec, J. P. Sollet, and G. Bleichner Impact of appropriateness of initial antibiotic therapy on the outcome of ventilatorassociated pneumonia. Intensive Care Med. 27: Frimodt-Moller, N., J. Knudsen, and F. Espersen The mouse peritonitis/sepsis model, p In O. Zak and M. Sande (ed.), Handbook of animal models of infection. Academic Press, New York, NY. 11. Gudmundsson, S., et al The post-antibiotic effect of antimicrobial combinations in a neutropenic murine thigh infection model. J. Antimicrob. Chemother. 31(Suppl. D): Gudmundsson, S., and H. Erlendsdottir Murine thigh infection

6 VOL. 55, 2011 IN VIVO EFFICACY OF NOVEL AMINOGLYCOSIDE ACHN model, p In O. Zak and M. Sande (ed.), Handbook of animal models of infection. Academic Press, Inc., New York, NY. 13. Infectious Diseases Society of America The Initiative: pursuing a global commitment to develop 10 new antibacterial drugs by Clin. Infect. Dis. 50: Institute of Laboratory Animal Research, Commission on Life Sciences, and National Research Council Guide for the care and use of laboratory animals. National Academy Press, Washington, DC. 15. Jana, S., and J. K. Deb Molecular understanding of aminoglycoside action and resistance. Appl. Microbiol. Biotechnol. 70: Jao, R. L., and G. G. Jackson Gentamicin sulfate, new antibiotic against Gram-negative bacilli. Laboratory, pharmacological, and clinical evaluation. JAMA 189: Kollef, K. E., et al Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria. Chest 134: Kollef, M. H Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients. Clin. Infect. Dis. 31(Suppl. 4):S131 S Leggett, J. E., S. Ebert, B. Fantin, and W. A. Craig Comparative dose-effect relations at several dosing intervals for beta-lactam, aminoglycoside and quinolone antibiotics against gram-negative bacilli in murine thighinfection and pneumonitis models. Scand. J. Infect. Dis. Suppl. 74: Leggett, J. E., et al Comparative antibiotic dose-effect relations at several dosing intervals in murine pneumonitis and thigh-infection models. J. Infect. Dis. 159: Mueller, E. W., et al Effect from multiple episodes of inadequate empiric antibiotic therapy for ventilator-associated pneumonia on morbidity and mortality among critically ill trauma patients. J. Trauma 58: Oplustil, C. P., R. Nunes, and C. Mendes Multicenter evaluation of resistance patterns of Klebsiella pneumoniae, Escherichia coli, Salmonella spp and Shigella spp isolated from clinical specimens in Brazil: RESISTNET Surveillance Program. Braz. J. Infect. Dis. 5: Patel, G., S. Huprikar, S. H. Factor, S. G. Jenkins, and D. P. Calfee Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect. Control Hosp. Epidemiol. 29: Rhomberg, P. R., and R. N. Jones Summary trends for the Meropenem Yearly Susceptibility Test Information Collection Program: a 10-year experience in the United States ( ). Diagn. Microbiol. Infect. Dis. 65: Schatz, A., E. Bugie, and S. A. Waksman Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Clin. Orthop. Relat. Res. 437: Schwaber, M. J., and Y. Carmeli Carbapenem-resistant Enterobacteriaceae: a potential threat. JAMA 300: Shin, J. H., et al High rates of plasmid-mediated quinolone resistance QnrB variants among ciprofloxacin-resistant Escherichia coli and Klebsiella pneumoniae from urinary tract infections in Korea. Microb. Drug Resist. 14: Spink, W. W., W. H. Hall, and V. Ferris Clinical significance of staphylococci with natural or acquired resistance to the sulfonamides and to penicillin. JAMA 128: Tsakris, A., J. Douboyas, and L. S. Tzouvelekis High rates of resistance to piperacillin/tazobactam among Escherichia coli and Klebsiella pneumoniae strains isolated in a Greek hospital. Diagn. Microbiol. Infect. Dis. 29: Urban, C., et al Carbapenem-resistant Escherichia coli harboring Klebsiella pneumoniae carbapenemase beta-lactamases associated with long-term care facilities. Clin. Infect. Dis. 46:e127 e Vogelman, B., et al Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model. J. Infect. Dis. 158: Downloaded from on December 15, 2018 by guest

Appropriate antimicrobial therapy in HAP: What does this mean?

Appropriate antimicrobial therapy in HAP: What does this mean? Appropriate antimicrobial therapy in HAP: What does this mean? Jaehee Lee, M.D. Kyungpook National University Hospital, Korea KNUH since 1907 Presentation outline Empiric antimicrobial choice: right spectrum,

More information

Activity of a novel aminoglycoside, ACHN-490, against clinical isolates of Escherichia coli and Klebsiella pneumoniae from New York City

Activity of a novel aminoglycoside, ACHN-490, against clinical isolates of Escherichia coli and Klebsiella pneumoniae from New York City Journal of Antimicrobial Chemotherapy Advance Access published July 31, 2010 J Antimicrob Chemother doi:10.1093/jac/dkq278 Activity of a novel aminoglycoside, ACHN-490, against clinical isolates of Escherichia

More information

Other β-lactamase Inhibitor (BLI) Combinations: Focus on VNRX-5133, WCK 5222 and ETX2514SUL

Other β-lactamase Inhibitor (BLI) Combinations: Focus on VNRX-5133, WCK 5222 and ETX2514SUL Other β-lactamase Inhibitor (BLI) Combinations: Focus on VNRX-5133, WCK 5222 and ETX2514SUL David P. Nicolau, PharmD, FCCP, FIDSA Director, Center for Anti-Infective Research and Development Hartford Hospital

More information

ETX2514SUL (sulbactam/etx2514) for the treatment of Acinetobacter baumannii infections

ETX2514SUL (sulbactam/etx2514) for the treatment of Acinetobacter baumannii infections ETX2514SUL (sulbactam/etx2514) for the treatment of Acinetobacter baumannii infections Robin Isaacs Chief Medical Officer, Entasis Therapeutics Dr. Isaacs is a full-time employee of Entasis Therapeutics.

More information

Mono- versus Bitherapy for Management of HAP/VAP in the ICU

Mono- versus Bitherapy for Management of HAP/VAP in the ICU Mono- versus Bitherapy for Management of HAP/VAP in the ICU Jean Chastre, www.reamedpitie.com Conflicts of interest: Consulting or Lecture fees: Nektar-Bayer, Pfizer, Brahms, Sanofi- Aventis, Janssen-Cilag,

More information

ETX0282, a Novel Oral Agent Against Multidrug-Resistant Enterobacteriaceae

ETX0282, a Novel Oral Agent Against Multidrug-Resistant Enterobacteriaceae ETX0282, a Novel Oral Agent Against Multidrug-Resistant Enterobacteriaceae Thomas Durand-Réville 02 June 2017 - ASM Microbe 2017 (Session #113) Disclosures Thomas Durand-Réville: Full-time Employee; Self;

More information

MICRONAUT MICRONAUT-S Detection of Resistance Mechanisms. Innovation with Integrity BMD MIC

MICRONAUT MICRONAUT-S Detection of Resistance Mechanisms. Innovation with Integrity BMD MIC MICRONAUT Detection of Resistance Mechanisms Innovation with Integrity BMD MIC Automated and Customized Susceptibility Testing For detection of resistance mechanisms and specific resistances of clinical

More information

Introduction to Pharmacokinetics and Pharmacodynamics

Introduction to Pharmacokinetics and Pharmacodynamics Introduction to Pharmacokinetics and Pharmacodynamics Diane M. Cappelletty, Pharm.D. Assistant Professor of Pharmacy Practice Wayne State University August, 2001 Vocabulary Clearance Renal elimination:

More information

Antimicrobial Cycling. Donald E Low University of Toronto

Antimicrobial Cycling. Donald E Low University of Toronto Antimicrobial Cycling Donald E Low University of Toronto Bad Bugs, No Drugs 1 The Antimicrobial Availability Task Force of the IDSA 1 identified as particularly problematic pathogens A. baumannii and

More information

ETX2514: Responding to the global threat of nosocomial multidrug and extremely drug resistant Gram-negative pathogens

ETX2514: Responding to the global threat of nosocomial multidrug and extremely drug resistant Gram-negative pathogens ETX2514: Responding to the global threat of nosocomial multidrug and extremely drug resistant Gram-negative pathogens Ruben Tommasi, PhD Chief Scientific Officer ECCMID 2017 April 24, 2017 Vienna, Austria

More information

Mechanism of antibiotic resistance

Mechanism of antibiotic resistance Mechanism of antibiotic resistance Dr.Siriwoot Sookkhee Ph.D (Biopharmaceutics) Department of Microbiology Faculty of Medicine, Chiang Mai University Antibiotic resistance Cross-resistance : resistance

More information

DR. MICHAEL A. BORG DIRECTOR OF INFECTION PREVENTION & CONTROL MATER DEI HOSPITAL - MALTA

DR. MICHAEL A. BORG DIRECTOR OF INFECTION PREVENTION & CONTROL MATER DEI HOSPITAL - MALTA DR. MICHAEL A. BORG DIRECTOR OF INFECTION PREVENTION & CONTROL MATER DEI HOSPITAL - MALTA The good old days The dread (of) infections that used to rage through the whole communities is muted Their retreat

More information

Burton's Microbiology for the Health Sciences. Chapter 9. Controlling Microbial Growth in Vivo Using Antimicrobial Agents

Burton's Microbiology for the Health Sciences. Chapter 9. Controlling Microbial Growth in Vivo Using Antimicrobial Agents Burton's Microbiology for the Health Sciences Chapter 9. Controlling Microbial Growth in Vivo Using Antimicrobial Agents Chapter 9 Outline Introduction Characteristics of an Ideal Antimicrobial Agent How

More information

Antimicrobial Pharmacodynamics

Antimicrobial Pharmacodynamics Antimicrobial Pharmacodynamics November 28, 2007 George P. Allen, Pharm.D. Assistant Professor, Pharmacy Practice OSU College of Pharmacy at OHSU Objectives Become familiar with PD parameters what they

More information

2012 ANTIBIOGRAM. Central Zone Former DTHR Sites. Department of Pathology and Laboratory Medicine

2012 ANTIBIOGRAM. Central Zone Former DTHR Sites. Department of Pathology and Laboratory Medicine 2012 ANTIBIOGRAM Central Zone Former DTHR Sites Department of Pathology and Laboratory Medicine Medically Relevant Pathogens Based on Gram Morphology Gram-negative Bacilli Lactose Fermenters Non-lactose

More information

Doripenem: A new carbapenem antibiotic a review of comparative antimicrobial and bactericidal activities

Doripenem: A new carbapenem antibiotic a review of comparative antimicrobial and bactericidal activities REVIEW Doripenem: A new carbapenem antibiotic a review of comparative antimicrobial and bactericidal activities Fiona Walsh Department of Clinical Microbiology, Trinity College Dublin, Dublin, Ireland

More information

Consequences of Antimicrobial Resistant Bacteria. Antimicrobial Resistance. Molecular Genetics of Antimicrobial Resistance. Topics to be Covered

Consequences of Antimicrobial Resistant Bacteria. Antimicrobial Resistance. Molecular Genetics of Antimicrobial Resistance. Topics to be Covered Antimicrobial Resistance Consequences of Antimicrobial Resistant Bacteria Change in the approach to the administration of empiric antimicrobial therapy Increased number of hospitalizations Increased length

More information

against Clinical Isolates of Gram-Positive Bacteria

against Clinical Isolates of Gram-Positive Bacteria ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Feb. 993, p. 366-370 Vol. 37, No. 0066-0/93/00366-05$0.00/0 Copyright 993, American Society for Microbiology In Vitro Activity of CP-99,9, a New Fluoroquinolone,

More information

MID 23. Antimicrobial Resistance. Consequences of Antimicrobial Resistant Bacteria. Molecular Genetics of Antimicrobial Resistance

MID 23. Antimicrobial Resistance. Consequences of Antimicrobial Resistant Bacteria. Molecular Genetics of Antimicrobial Resistance Antimicrobial Resistance Molecular Genetics of Antimicrobial Resistance Micro evolutionary change - point mutations Beta-lactamase mutation extends spectrum of the enzyme rpob gene (RNA polymerase) mutation

More information

Multi-drug resistant microorganisms

Multi-drug resistant microorganisms Multi-drug resistant microorganisms Arzu TOPELI Director of MICU Hacettepe University Faculty of Medicine, Ankara-Turkey Council Member of WFSICCM Deaths in the US declined by 220 per 100,000 with the

More information

Tel: Fax:

Tel: Fax: CONCISE COMMUNICATION Bactericidal activity and synergy studies of BAL,a novel pyrrolidinone--ylidenemethyl cephem,tested against streptococci, enterococci and methicillin-resistant staphylococci L. M.

More information

Selective toxicity. Antimicrobial Drugs. Alexander Fleming 10/17/2016

Selective toxicity. Antimicrobial Drugs. Alexander Fleming 10/17/2016 Selective toxicity Antimicrobial Drugs Chapter 20 BIO 220 Drugs must work inside the host and harm the infective pathogens, but not the host Antibiotics are compounds produced by fungi or bacteria that

More information

Antimicrobial Resistance

Antimicrobial Resistance Antimicrobial Resistance Consequences of Antimicrobial Resistant Bacteria Change in the approach to the administration of empiric antimicrobial therapy Increased number of hospitalizations Increased length

More information

Antimicrobial Resistance Acquisition of Foreign DNA

Antimicrobial Resistance Acquisition of Foreign DNA Antimicrobial Resistance Acquisition of Foreign DNA Levy, Scientific American Horizontal gene transfer is common, even between Gram positive and negative bacteria Plasmid - transfer of single or multiple

More information

In Vitro Antimicrobial Activity of CP-99,219, a Novel Azabicyclo-Naphthyridone

In Vitro Antimicrobial Activity of CP-99,219, a Novel Azabicyclo-Naphthyridone ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Feb. 993, p. 39-353 0066-0/93/0039-05$0.00/0 Copyright 993, American Society for Microbiology Vol. 37, No. In Vitro Antimicrobial Activity of, a Novel Azabicyclo-Naphthyridone

More information

National Surveillance of Antimicrobial Resistance in Pseudomonas aeruginosa Isolates Obtained from Intensive Care Unit Patients from 1993 to 2002

National Surveillance of Antimicrobial Resistance in Pseudomonas aeruginosa Isolates Obtained from Intensive Care Unit Patients from 1993 to 2002 ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Dec. 2004, p. 4606 4610 Vol. 48, No. 12 0066-4804/04/$08.00 0 DOI: 10.1128/AAC.48.12.4606 4610.2004 Copyright 2004, American Society for Microbiology. All Rights

More information

Prevalence of Metallo-Beta-Lactamase Producing Pseudomonas aeruginosa and its antibiogram in a tertiary care centre

Prevalence of Metallo-Beta-Lactamase Producing Pseudomonas aeruginosa and its antibiogram in a tertiary care centre International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 4 Number 9 (2015) pp. 952-956 http://www.ijcmas.com Original Research Article Prevalence of Metallo-Beta-Lactamase

More information

Title: N-Acetylcysteine (NAC) Mediated Modulation of Bacterial Antibiotic

Title: N-Acetylcysteine (NAC) Mediated Modulation of Bacterial Antibiotic AAC Accepts, published online ahead of print on June 00 Antimicrob. Agents Chemother. doi:0./aac.0070-0 Copyright 00, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights

More information

Safe Patient Care Keeping our Residents Safe Use Standard Precautions for ALL Residents at ALL times

Safe Patient Care Keeping our Residents Safe Use Standard Precautions for ALL Residents at ALL times Safe Patient Care Keeping our Residents Safe 2016 Use Standard Precautions for ALL Residents at ALL times #safepatientcare Do bugs need drugs? Dr Deirdre O Brien Consultant Microbiologist Mercy University

More information

Nosocomial Infections: What Are the Unmet Needs

Nosocomial Infections: What Are the Unmet Needs Nosocomial Infections: What Are the Unmet Needs Jean Chastre, MD Service de Réanimation Médicale Hôpital Pitié-Salpêtrière, AP-HP, Université Pierre et Marie Curie, Paris 6, France www.reamedpitie.com

More information

Intrinsic, implied and default resistance

Intrinsic, implied and default resistance Appendix A Intrinsic, implied and default resistance Magiorakos et al. [1] and CLSI [2] are our primary sources of information on intrinsic resistance. Sanford et al. [3] and Gilbert et al. [4] have been

More information

4/3/2017 CLINICAL PEARLS: UPDATES IN THE MANAGEMENT OF NOSOCOMIAL PNEUMONIA DISCLOSURE LEARNING OBJECTIVES

4/3/2017 CLINICAL PEARLS: UPDATES IN THE MANAGEMENT OF NOSOCOMIAL PNEUMONIA DISCLOSURE LEARNING OBJECTIVES CLINICAL PEARLS: UPDATES IN THE MANAGEMENT OF NOSOCOMIAL PNEUMONIA BILLIE BARTEL, PHARMD, BCCCP APRIL 7 TH, 2017 DISCLOSURE I have had no financial relationship over the past 12 months with any commercial

More information

Florida Health Care Association District 2 January 13, 2015 A.C. Burke, MA, CIC

Florida Health Care Association District 2 January 13, 2015 A.C. Burke, MA, CIC Florida Health Care Association District 2 January 13, 2015 A.C. Burke, MA, CIC 11/20/2014 1 To describe carbapenem-resistant Enterobacteriaceae. To identify laboratory detection standards for carbapenem-resistant

More information

Concise Antibiogram Toolkit Background

Concise Antibiogram Toolkit Background Background This toolkit is designed to guide nursing homes in creating their own antibiograms, an important tool for guiding empiric antimicrobial therapy. Information about antibiograms and instructions

More information

Antibiotic Resistance. Antibiotic Resistance: A Growing Concern. Antibiotic resistance is not new 3/21/2011

Antibiotic Resistance. Antibiotic Resistance: A Growing Concern. Antibiotic resistance is not new 3/21/2011 Antibiotic Resistance Antibiotic Resistance: A Growing Concern Judy Ptak RN MSN Infection Prevention Practitioner Dartmouth-Hitchcock Medical Center Lebanon, NH Occurs when a microorganism fails to respond

More information

9/30/2016. Dr. Janell Mayer, Pharm.D., CGP, BCPS Dr. Lindsey Votaw, Pharm.D., CGP, BCPS

9/30/2016. Dr. Janell Mayer, Pharm.D., CGP, BCPS Dr. Lindsey Votaw, Pharm.D., CGP, BCPS Dr. Janell Mayer, Pharm.D., CGP, BCPS Dr. Lindsey Votaw, Pharm.D., CGP, BCPS 1 2 Untoward Effects of Antibiotics Antibiotic resistance Adverse drug events (ADEs) Hypersensitivity/allergy Drug side effects

More information

Evaluation of a computerized antimicrobial susceptibility system with bacteria isolated from animals

Evaluation of a computerized antimicrobial susceptibility system with bacteria isolated from animals J Vet Diagn Invest :164 168 (1998) Evaluation of a computerized antimicrobial susceptibility system with bacteria isolated from animals Susannah K. Hubert, Phouc Dinh Nguyen, Robert D. Walker Abstract.

More information

CONTAGIOUS COMMENTS Department of Epidemiology

CONTAGIOUS COMMENTS Department of Epidemiology VOLUME XXIII NUMBER 1 July 2008 CONTAGIOUS COMMENTS Department of Epidemiology Bugs and Drugs Elaine Dowell, SM (ASCP), Marti Roe SM (ASCP), Ann-Christine Nyquist MD, MSPH Are the bugs winning? The 2007

More information

Witchcraft for Gram negatives

Witchcraft for Gram negatives Witchcraft for Gram negatives Dr Subramanian S MD DNB MNAMS AB (Medicine, Infect Dis) Infectious Diseases Consultant Global Health City, Chennai www.asksubra.com Drug resistance follows the drug like a

More information

Original Articles. K A M S W Gunarathne 1, M Akbar 2, K Karunarathne 3, JRS de Silva 4. Sri Lanka Journal of Child Health, 2011; 40(4):

Original Articles. K A M S W Gunarathne 1, M Akbar 2, K Karunarathne 3, JRS de Silva 4. Sri Lanka Journal of Child Health, 2011; 40(4): Original Articles Analysis of blood/tracheal culture results to assess common pathogens and pattern of antibiotic resistance at medical intensive care unit, Lady Ridgeway Hospital for Children K A M S

More information

Update on Resistance and Epidemiology of Nosocomial Respiratory Pathogens in Asia. Po-Ren Hsueh. National Taiwan University Hospital

Update on Resistance and Epidemiology of Nosocomial Respiratory Pathogens in Asia. Po-Ren Hsueh. National Taiwan University Hospital Update on Resistance and Epidemiology of Nosocomial Respiratory Pathogens in Asia Po-Ren Hsueh National Taiwan University Hospital Ventilator-associated Pneumonia Microbiological Report Sputum from a

More information

EARS Net Report, Quarter

EARS Net Report, Quarter EARS Net Report, Quarter 4 213 March 214 Key Points for 213* Escherichia coli: The proportion of patients with invasive infections caused by E. coli producing extended spectrum β lactamases (ESBLs) increased

More information

Sepsis is the most common cause of death in

Sepsis is the most common cause of death in ADDRESSING ANTIMICROBIAL RESISTANCE IN THE INTENSIVE CARE UNIT * John P. Quinn, MD ABSTRACT Two of the more common strategies for optimizing antimicrobial therapy in the intensive care unit (ICU) are antibiotic

More information

The International Collaborative Conference in Clinical Microbiology & Infectious Diseases

The International Collaborative Conference in Clinical Microbiology & Infectious Diseases The International Collaborative Conference in Clinical Microbiology & Infectious Diseases PLUS: Antimicrobial stewardship in hospitals: Improving outcomes through better education and implementation of

More information

Other Beta - lactam Antibiotics

Other Beta - lactam Antibiotics Other Beta - lactam Antibiotics Assistant Professor Dr. Naza M. Ali Lec 5 8 Nov 2017 Lecture outlines Other beta lactam antibiotics Other inhibitors of cell wall synthesis Other beta-lactam Antibiotics

More information

Defining Extended Spectrum b-lactamases: Implications of Minimum Inhibitory Concentration- Based Screening Versus Clavulanate Confirmation Testing

Defining Extended Spectrum b-lactamases: Implications of Minimum Inhibitory Concentration- Based Screening Versus Clavulanate Confirmation Testing Infect Dis Ther (2015) 4:513 518 DOI 10.1007/s40121-015-0094-6 BRIEF REPORT Defining Extended Spectrum b-lactamases: Implications of Minimum Inhibitory Concentration- Based Screening Versus Clavulanate

More information

Influence of ph on Adaptive Resistance of Pseudomonas aeruginosa to Aminoglycosides and Their Postantibiotic Effects

Influence of ph on Adaptive Resistance of Pseudomonas aeruginosa to Aminoglycosides and Their Postantibiotic Effects ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Jan. 1996, p. 35 39 Vol. 40, No. 1 0066-4804/96/$04.00 0 Copyright 1996, American Society for Microbiology Influence of ph on Adaptive Resistance of Pseudomonas aeruginosa

More information

Does the Dose Matter?

Does the Dose Matter? SUPPLEMENT ARTICLE Does the Dose Matter? William A. Craig Department of Medicine, University of Wisconsin, Madison, Wisconsin Pharmacokinetic/pharmacodynamic (PK/PD) parameters, such as the ratio of peak

More information

2 0 hr. 2 hr. 4 hr. 8 hr. 10 hr. 12 hr.14 hr. 16 hr. 18 hr. 20 hr. 22 hr. 24 hr. (time)

2 0 hr. 2 hr. 4 hr. 8 hr. 10 hr. 12 hr.14 hr. 16 hr. 18 hr. 20 hr. 22 hr. 24 hr. (time) Key words I μ μ μ μ μ μ μ μ μ μ μ μ μ μ II Fig. 1. Microdilution plate. The dilution step of the antimicrobial agent is prepared in the -well microplate. Serial twofold dilution were prepared according

More information

Comparison of Antibiotic Resistance and Sensitivity with Reference to Ages of Elders

Comparison of Antibiotic Resistance and Sensitivity with Reference to Ages of Elders Daffodil International University Institutional Repository DIU Journal of Science and Technology Volume 10, Issue 1-2, July 2015 2016-06-16 Comparison of Antibiotic Resistance and Sensitivity with Reference

More information

GUIDE TO INFECTION CONTROL IN THE HOSPITAL. Antibiotic Resistance

GUIDE TO INFECTION CONTROL IN THE HOSPITAL. Antibiotic Resistance GUIDE TO INFECTION CONTROL IN THE HOSPITAL CHAPTER 4: Antibiotic Resistance Author M.P. Stevens, MD, MPH S. Mehtar, MD R.P. Wenzel, MD, MSc Chapter Editor Michelle Doll, MD, MPH Topic Outline Key Issues

More information

Learning Points. Raymond Blum, M.D. Antimicrobial resistance among gram-negative pathogens is increasing

Learning Points. Raymond Blum, M.D. Antimicrobial resistance among gram-negative pathogens is increasing Raymond Blum, M.D. Learning Points Antimicrobial resistance among gram-negative pathogens is increasing Infection with antimicrobial-resistant pathogens is associated with increased mortality, length of

More information

Rise of Resistance: From MRSA to CRE

Rise of Resistance: From MRSA to CRE Rise of Resistance: From MRSA to CRE Paul D. Holtom, MD Professor of Medicine and Orthopaedics USC Keck School of Medicine SUPERBUGS (AKA MDROs) MRSA Methicillin-resistant S. aureus Evolution of Drug Resistance

More information

VOL. XXIII NO. II THE JOURNAL OF ANTIBIOTICS 559. ANTIBIOTIC 6640.* Ill

VOL. XXIII NO. II THE JOURNAL OF ANTIBIOTICS 559. ANTIBIOTIC 6640.* Ill VOL. XXIII NO. II THE JOURNAL OF ANTIBIOTICS 559 ANTIBIOTIC 6640.* Ill BIOLOGICAL STUDIES WITH ANTIBIOTIC 6640, A NEW BROAD-SPECTRUM AMINOGLYCOSIDE ANTIBIOTIC J. Allan Waitz, Eugene L. Moss, Jr., Edwin

More information

β-lactams resistance among Enterobacteriaceae in Morocco 1 st ICREID Addis Ababa March 2018

β-lactams resistance among Enterobacteriaceae in Morocco 1 st ICREID Addis Ababa March 2018 β-lactams resistance among Enterobacteriaceae in Morocco 1 st ICREID Addis Ababa 12-14 March 2018 Antibiotic resistance center Institut Pasteur du Maroc Enterobacteriaceae (E. coli, Salmonella, ) S. aureus

More information

The Basics: Using CLSI Antimicrobial Susceptibility Testing Standards

The Basics: Using CLSI Antimicrobial Susceptibility Testing Standards The Basics: Using CLSI Antimicrobial Susceptibility Testing Standards Janet A. Hindler, MCLS, MT(ASCP) UCLA Health System Los Angeles, California, USA jhindler@ucla.edu 1 Learning Objectives Describe information

More information

Scottish Medicines Consortium

Scottish Medicines Consortium Scottish Medicines Consortium tigecycline 50mg vial of powder for intravenous infusion (Tygacil ) (277/06) Wyeth 9 June 2006 The Scottish Medicines Consortium (SMC) has completed its assessment of the

More information

WHY IS THIS IMPORTANT?

WHY IS THIS IMPORTANT? CHAPTER 20 ANTIBIOTIC RESISTANCE WHY IS THIS IMPORTANT? The most important problem associated with infectious disease today is the rapid development of resistance to antibiotics It will force us to change

More information

GENERAL NOTES: 2016 site of infection type of organism location of the patient

GENERAL NOTES: 2016 site of infection type of organism location of the patient GENERAL NOTES: This is a summary of the antibiotic sensitivity profile of clinical isolates recovered at AIIMS Bhopal Hospital during the year 2016. However, for organisms in which < 30 isolates were recovered

More information

Antibiotics. Antimicrobial Drugs. Alexander Fleming 10/18/2017

Antibiotics. Antimicrobial Drugs. Alexander Fleming 10/18/2017 Antibiotics Antimicrobial Drugs Chapter 20 BIO 220 Antibiotics are compounds produced by fungi or bacteria that inhibit or kill competing microbial species Antimicrobial drugs must display selective toxicity,

More information

Understanding the Hospital Antibiogram

Understanding the Hospital Antibiogram Understanding the Hospital Antibiogram Sharon Erdman, PharmD Clinical Professor Purdue University College of Pharmacy Infectious Diseases Clinical Pharmacist Eskenazi Health 5 Understanding the Hospital

More information

Int.J.Curr.Microbiol.App.Sci (2017) 6(3):

Int.J.Curr.Microbiol.App.Sci (2017) 6(3): International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 6 Number 3 (2017) pp. 891-895 Journal homepage: http://www.ijcmas.com Original Research Article https://doi.org/10.20546/ijcmas.2017.603.104

More information

Outline. Antimicrobial resistance. Antimicrobial resistance in gram negative bacilli. % susceptibility 7/11/2010

Outline. Antimicrobial resistance. Antimicrobial resistance in gram negative bacilli. % susceptibility 7/11/2010 Multi-Drug Resistant Organisms Is Combination Therapy the Way to Go? Sutthiporn Pattharachayakul, PharmD Prince of Songkhla University, Thailand Outline Prevalence of anti-microbial resistance in Acinetobacter

More information

Imagine. Multi-Drug Resistant Superbugs- What s the Big Deal? A World. Without Antibiotics. Where Simple Infections can be Life Threatening

Imagine. Multi-Drug Resistant Superbugs- What s the Big Deal? A World. Without Antibiotics. Where Simple Infections can be Life Threatening Multi-Drug Resistant Superbugs- What s the Big Deal? Toni Biasi, RN MSN MPH CIC Infection Prevention Indiana University Health Imagine A World Without Antibiotics A World Where Simple Infections can be

More information

An evaluation of the susceptibility patterns of Gram-negative organisms isolated in cancer centres with aminoglycoside usage

An evaluation of the susceptibility patterns of Gram-negative organisms isolated in cancer centres with aminoglycoside usage Journal of Antimicrobial Chemotherapy (1991) 27, Suppl. C, 1-7 An evaluation of the susceptibility patterns of Gram-negative organisms isolated in cancer centres with aminoglycoside usage J. J. Muscato",

More information

Fighting MDR Pathogens in the ICU

Fighting MDR Pathogens in the ICU Fighting MDR Pathogens in the ICU Dr. Murat Akova Hacettepe University School of Medicine, Department of Infectious Diseases, Ankara, Turkey 1 50.000 deaths each year in US and Europe due to antimicrobial

More information

Antimicrobial Stewardship Strategy: Antibiograms

Antimicrobial Stewardship Strategy: Antibiograms Antimicrobial Stewardship Strategy: Antibiograms A summary of the cumulative susceptibility of bacterial isolates to formulary antibiotics in a given institution or region. Its main functions are to guide

More information

New Drugs for Bad Bugs- Statewide Antibiogram

New Drugs for Bad Bugs- Statewide Antibiogram New Drugs for Bad Bugs- Statewide Antibiogram Felicia Matthews, Pharm.D., BCPS Senior Consultant, Pharmacy Specialty BE MedMined Services Disclosures Employee of BD Corporation MedMined Services Agenda

More information

OPTIMIZATION OF PK/PD OF ANTIBIOTICS FOR RESISTANT GRAM-NEGATIVE ORGANISMS

OPTIMIZATION OF PK/PD OF ANTIBIOTICS FOR RESISTANT GRAM-NEGATIVE ORGANISMS HTIDE CONFERENCE 2018 OPTIMIZATION OF PK/PD OF ANTIBIOTICS FOR RESISTANT GRAM-NEGATIVE ORGANISMS FEDERICO PEA INSTITUTE OF CLINICAL PHARMACOLOGY DEPARTMENT OF MEDICINE, UNIVERSITY OF UDINE, ITALY SANTA

More information

ESBL Producers An Increasing Problem: An Overview Of An Underrated Threat

ESBL Producers An Increasing Problem: An Overview Of An Underrated Threat ESBL Producers An Increasing Problem: An Overview Of An Underrated Threat Hicham Ezzat Professor of Microbiology and Immunology Cairo University Introduction 1 Since the 1980s there have been dramatic

More information

In Vitro Activity of Netilmicin, Gentamicin, and Amikacin

In Vitro Activity of Netilmicin, Gentamicin, and Amikacin ANTIMICROBIAL AGzNTS AND CHEMOTHERAPY, Jan. 1977, p. 126-131 Copyright X 1977 American Society for Microbiology Vol. 11, No. 1 Printed in U.S.A. In Vitro Activity of Netilmicin, Gentamicin, and Amikacin

More information

The β- Lactam Antibiotics. Munir Gharaibeh MD, PhD, MHPE School of Medicine, The University of Jordan November 2018

The β- Lactam Antibiotics. Munir Gharaibeh MD, PhD, MHPE School of Medicine, The University of Jordan November 2018 The β- Lactam Antibiotics Munir Gharaibeh MD, PhD, MHPE School of Medicine, The University of Jordan November 2018 Penicillins. Cephalosporins. Carbapenems. Monobactams. The β- Lactam Antibiotics 2 3 How

More information

PDF hosted at the Radboud Repository of the Radboud University Nijmegen

PDF hosted at the Radboud Repository of the Radboud University Nijmegen PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/26062

More information

EXTENDED-SPECTRUM BETA-LACTAMASE (ESBL) TESTING

EXTENDED-SPECTRUM BETA-LACTAMASE (ESBL) TESTING EXTENDED-SPECTRUM BETA-LACTAMASE (ESBL) TESTING CHN61: EXTENDED-SPECTRUM BETA-LACTAMASE (ESBL) TESTING 1.1 Introduction A common mechanism of bacterial resistance to beta-lactam antibiotics is the production

More information

The pharmacological and microbiological basis of PK/PD : why did we need to invent PK/PD in the first place? Paul M. Tulkens

The pharmacological and microbiological basis of PK/PD : why did we need to invent PK/PD in the first place? Paul M. Tulkens The pharmacological and microbiological basis of PK/PD : why did we need to invent PK/PD in the first place? Paul M. Tulkens Cellular and Molecular Pharmacology Unit Catholic University of Louvain, Brussels,

More information

Microbiology ( Bacteriology) sheet # 7

Microbiology ( Bacteriology) sheet # 7 Microbiology ( Bacteriology) sheet # 7 Revision of last lecture : Each type of antimicrobial drug normally targets a specific structure or component of the bacterial cell eg:( cell wall, cell membrane,

More information

Educating Clinical and Public Health Laboratories About Antimicrobial Resistance Challenges

Educating Clinical and Public Health Laboratories About Antimicrobial Resistance Challenges Educating Clinical and Public Health Laboratories About Antimicrobial Resistance Challenges Janet Hindler, MCLS MT(ASCP) UCLA Medical Center jhindler@ucla.edu also working as a consultant with the Association

More information

Original Article. Ratri Hortiwakul, M.Sc.*, Pantip Chayakul, M.D.*, Natnicha Ingviya, B.Sc.**

Original Article. Ratri Hortiwakul, M.Sc.*, Pantip Chayakul, M.D.*, Natnicha Ingviya, B.Sc.** Original Article In Vitro Activity of Cefminox and Other β-lactam Antibiotics Against Clinical Isolates of Extended- Spectrum-β-lactamase-Producing Klebsiella pneumoniae and Escherichia coli Ratri Hortiwakul,

More information

MICHAEL J. RYBAK,* ELLIE HERSHBERGER, TABITHA MOLDOVAN, AND RICHARD G. GRUCZ

MICHAEL J. RYBAK,* ELLIE HERSHBERGER, TABITHA MOLDOVAN, AND RICHARD G. GRUCZ ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Apr. 2000, p. 1062 1066 Vol. 44, No. 4 0066-4804/00/$04.00 0 Copyright 2000, American Society for Microbiology. All Rights Reserved. In Vitro Activities of Daptomycin,

More information

ESBL- and carbapenemase-producing microorganisms; state of the art. Laurent POIREL

ESBL- and carbapenemase-producing microorganisms; state of the art. Laurent POIREL ESBL- and carbapenemase-producing microorganisms; state of the art Laurent POIREL Medical and Molecular Microbiology Unit Dept of Medicine University of Fribourg Switzerland INSERM U914 «Emerging Resistance

More information

Introduction to Chemotherapeutic Agents. Munir Gharaibeh MD, PhD, MHPE School of Medicine, The university of Jordan November 2018

Introduction to Chemotherapeutic Agents. Munir Gharaibeh MD, PhD, MHPE School of Medicine, The university of Jordan November 2018 Introduction to Chemotherapeutic Agents Munir Gharaibeh MD, PhD, MHPE School of Medicine, The university of Jordan November 2018 Antimicrobial Agents Substances that kill bacteria without harming the host.

More information

Antimicrobial stewardship in managing septic patients

Antimicrobial stewardship in managing septic patients Antimicrobial stewardship in managing septic patients November 11, 2017 Samuel L. Aitken, PharmD, BCPS (AQ-ID) Clinical Pharmacy Specialist, Infectious Diseases slaitken@mdanderson.org Conflict of interest

More information

What s next in the antibiotic pipeline?

What s next in the antibiotic pipeline? What s next in the antibiotic pipeline? Jennifer Tieu, Pharm.D., BCPS Clinical Pearls OSHP Spring Meeting Mercy Hospital April 13, 2018 Objective 2 Describe the drug class and mechanism of action of antibiotics

More information

Prevalence of Extended Spectrum Beta- Lactamase Producers among Various Clinical Samples in a Tertiary Care Hospital: Kurnool District, India

Prevalence of Extended Spectrum Beta- Lactamase Producers among Various Clinical Samples in a Tertiary Care Hospital: Kurnool District, India International Journal of Current Microbiology and Applied Sciences ISSN: 319-77 Volume Number (17) pp. 57-3 Journal homepage: http://www.ijcmas.com Original Research Article https://doi.org/1.5/ijcmas.17..31

More information

Mercy Medical Center Des Moines, Iowa Department of Pathology. Microbiology Department Antibiotic Susceptibility January December 2016

Mercy Medical Center Des Moines, Iowa Department of Pathology. Microbiology Department Antibiotic Susceptibility January December 2016 Mercy Medical Center Des Moines, Iowa Department of Pathology Microbiology Department Antibiotic Susceptibility January December 2016 These statistics are intended solely as a GUIDE to choosing appropriate

More information

ANTIBIOTIC RESISTANCE. Syed Ziaur Rahman, MD, PhD D/O Pharmacology, JNMC, AMU, Aligarh

ANTIBIOTIC RESISTANCE. Syed Ziaur Rahman, MD, PhD D/O Pharmacology, JNMC, AMU, Aligarh ANTIBIOTIC RESISTANCE Syed Ziaur Rahman, MD, PhD D/O Pharmacology, JNMC, AMU, Aligarh WHY IS THIS IMPORTANT? The most important problem associated with infectious disease today is the rapid development

More information

Management of Hospital-acquired Pneumonia

Management of Hospital-acquired Pneumonia Management of Hospital-acquired Pneumonia Adel Alothman, MB, FRCPC, FACP Asst. Professor, COM, KSAU-HS Head, Infectious Diseases, Department of Medicine King Abdulaziz Medical City Riyadh Saudi Arabia

More information

Protein Synthesis Inhibitors

Protein Synthesis Inhibitors Protein Synthesis Inhibitors Assistant Professor Dr. Naza M. Ali 11 Nov 2018 Lec 7 Aminoglycosides Are structurally related two amino sugars attached by glycosidic linkages. They are bactericidal Inhibitors

More information

Animal models and PK/PD. Examples with selected antibiotics

Animal models and PK/PD. Examples with selected antibiotics Animal models and PK/PD PD Examples with selected antibiotics Examples of animal models Amoxicillin Amoxicillin-clavulanate Macrolides Quinolones Andes D, Craig WA. AAC 199, :375 Amoxicillin in mouse thigh

More information

Antimicrobial stewardship: Quick, don t just do something! Stand there!

Antimicrobial stewardship: Quick, don t just do something! Stand there! Antimicrobial stewardship: Quick, don t just do something! Stand there! Stanley I. Martin, MD, FACP, FIDSA Director, Division of Infectious Diseases Director, Antimicrobial Stewardship Program Geisinger

More information

Aerobic bacterial infections in a burns unit of Sassoon General Hospital, Pune

Aerobic bacterial infections in a burns unit of Sassoon General Hospital, Pune Original article Aerobic bacterial infections in a burns unit of Sassoon General Hospital, Pune Patil P, Joshi S, Bharadwaj R. Department of Microbiology, B.J. Medical College, Pune, India. Corresponding

More information

Mike Apley Kansas State University

Mike Apley Kansas State University Mike Apley Kansas State University 2003 - Daptomycin cyclic lipopeptides 2000 - Linezolid - oxazolidinones 1985 Imipenem - carbapenems 1978 - Norfloxacin - fluoroquinolones 1970 Cephalexin - cephalosporins

More information

Dynamic Drug Combination Response on Pathogenic Mutations of Staphylococcus aureus

Dynamic Drug Combination Response on Pathogenic Mutations of Staphylococcus aureus 2011 International Conference on Biomedical Engineering and Technology IPCBEE vol.11 (2011) (2011) IACSIT Press, Singapore Dynamic Drug Combination Response on Pathogenic Mutations of Staphylococcus aureus

More information

Surveillance of Antimicrobial Resistance among Bacterial Pathogens Isolated from Hospitalized Patients at Chiang Mai University Hospital,

Surveillance of Antimicrobial Resistance among Bacterial Pathogens Isolated from Hospitalized Patients at Chiang Mai University Hospital, Original Article Vol. 28 No. 1 Surveillance of Antimicrobial Resistance:- Chaiwarith R, et al. 3 Surveillance of Antimicrobial Resistance among Bacterial Pathogens Isolated from Hospitalized Patients at

More information

RETROSPECTIVE STUDY OF GRAM NEGATIVE BACILLI ISOLATES AMONG DIFFERENT CLINICAL SAMPLES FROM A DIAGNOSTIC CENTER OF KANPUR

RETROSPECTIVE STUDY OF GRAM NEGATIVE BACILLI ISOLATES AMONG DIFFERENT CLINICAL SAMPLES FROM A DIAGNOSTIC CENTER OF KANPUR Original article RETROSPECTIVE STUDY OF GRAM NEGATIVE BACILLI ISOLATES AMONG DIFFERENT CLINICAL SAMPLES FROM A DIAGNOSTIC CENTER OF KANPUR R.Sujatha 1,Nidhi Pal 2, Deepak S 3 1. Professor & Head, Department

More information

2015 Antimicrobial Susceptibility Report

2015 Antimicrobial Susceptibility Report Gram negative Sepsis Outcome Programme (GNSOP) 2015 Antimicrobial Susceptibility Report Prepared by A/Professor Thomas Gottlieb Concord Hospital Sydney Jan Bell The University of Adelaide Adelaide On behalf

More information

PRACTIC GUIDELINES for APPROPRIATE ANTIBIOTICS USE

PRACTIC GUIDELINES for APPROPRIATE ANTIBIOTICS USE PRACTIC GUIDELINES for APPROPRIATE ANTIBIOTICS USE Global Alliance for Infection in Surgery World Society of Emergency Surgery (WSES) and not only!! Aims - 1 Rationalize the risk of antibiotics overuse

More information

Available online at ISSN No:

Available online at  ISSN No: Available online at www.ijmrhs.com ISSN No: 2319-5886 International Journal of Medical Research & Health Sciences, 2017, 6(4): 36-42 Comparative Evaluation of In-Vitro Doripenem Susceptibility with Other

More information

ANTIBIOTICS USED FOR RESISTACE BACTERIA. 1. Vancomicin

ANTIBIOTICS USED FOR RESISTACE BACTERIA. 1. Vancomicin ANTIBIOTICS USED FOR RESISTACE BACTERIA 1. Vancomicin Vancomycin is used to treat infections caused by bacteria. It belongs to the family of medicines called antibiotics. Vancomycin works by killing bacteria

More information

Antimicrobial Resistance

Antimicrobial Resistance Antimicrobial Resistance Consequences of Antimicrobial Resistant Bacteria Change in the approach to the administration of Change in the approach to the administration of empiric antimicrobial therapy Increased

More information