scholarly journals In Vitro Activity of Doripenem, a Carbapenem for the Treatment of Challenging Infections Caused by Gram-Negative Bacteria, against Recent Clinical Isolates from the United States

2008 ◽  
Vol 52 (12) ◽  
pp. 4388-4399 ◽  
Author(s):  
Chris M. Pillar ◽  
Mohana K. Torres ◽  
Nina P. Brown ◽  
Dineshchandra Shah ◽  
Daniel F. Sahm
Keyword(s):  
The United States ◽  
Clinical Isolates ◽  
Gram Negative Bacteria ◽  
Ventilator Associated Pneumonia ◽  
Coagulase Negative Staphylococci ◽  
Hospital Acquired Pneumonia ◽  
Abdominal Infections ◽  
Hospital Acquired ◽  
Gram Positive Cocci

ABSTRACT Doripenem, a 1β-methylcarbapenem, is a broad-spectrum antibiotic approved for the treatment of complicated urinary tract and complicated intra-abdominal infections. An indication for hospital-acquired pneumonia including ventilator-associated pneumonia is pending. The current study examined the activity of doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis. Doripenem and comparators were tested against 12,581 U.S. clinical isolates collected between 2005 and 2006 including isolates of Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. MICs (μg/ml) were established by broth microdilution. By MIC90, doripenem was comparable to imipenem and meropenem in activity against S. aureus (methicillin susceptible, 0.06; resistant, 8) and S. pneumoniae (penicillin susceptible, ≤0.015; resistant, 1). Against ceftazidime-susceptible Enterobacteriaceae, the MIC90 of doripenem (0.12) was comparable to that of meropenem (0.12) and superior to that of imipenem (2), though susceptibility of isolates exceeded 99% for all evaluated carbapenems. The activity of doripenem was not notably altered against ceftazidime-nonsusceptible or extended-spectrum β-lactamase screen-positive Enterobacteriaceae. Doripenem was the most potent carbapenem tested against P. aeruginosa (MIC90/% susceptibility [%S]: ceftazidime susceptible = 2/92%S, nonsusceptible = 16/61%S; imipenem susceptible = 1/98.5%S, nonsusceptible = 8/56%S). Against imipenem-susceptible Acinetobacter spp., doripenem (MIC90 = 2, 89.1%S) was twice as active by MIC90 as were imipenem and meropenem. Overall, doripenem potency was comparable to those of meropenem and imipenem against gram-positive cocci and doripenem was equal or superior in activity to meropenem and imipenem against Enterobacteriaceae, including β-lactam-nonsusceptible isolates. Doripenem was the most active carbapenem tested against P. aeruginosa regardless of β-lactam resistance.

Microbiology of Ventilator–Associated Pneumonia Compared With That of Hospital-Acquired Pneumonia

2007 ◽  
Vol 28 (7) ◽  
pp. 825-831 ◽  
Author(s):  
David J. Weber ◽  
William A. Rutala ◽  
Emily E. Sickbert-Bennett ◽  
Gregory P. Samsa ◽  
Vickie Brown ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Empirical Therapy ◽  
Ventilator Associated Pneumonia ◽  
Gram Positive ◽  
Similar Frequency ◽  
Gram Negative ◽  
Hospital Acquired Pneumonia ◽  
Hospital Acquired ◽  
Gram Positive Cocci ◽  
Ventilated Patients

Objective.Nosocomial pneumonia is the leading cause of mortality attributed to nosocomial infection. Appropriate empirical therapy has been associated with improved survival, but data are limited regarding the etiologic agents of hospital-acquired pneumonia in non-ventilated patients (HAP). This evaluation assessed whether the currently recommended empirical therapy is appropriate for both ventilator-associated pneumonia (VAP) and HAP by evaluating the infecting flora.Design.Prospectively collected hospitalwide surveillance data was obtained by infection control professionals using standard Centers for Disease Control and Prevention definitions.Setting.A tertiary care academic hospital.Patients.All patients admitted from 2000 through 2003.Results.A total of 588 episodes of pneumonia were reported in 556 patients: 327 episodes of VAP in 309 patients, and 261 episodes of HAP in 247 Patients. The infecting flora in ventilated patients included gram-positive cocci (32.0% [oxacillin-susceptible Staphylococcus aureus {OSSA}, 9.25%; oxacillin-resistant Staphylococcus aureus {ORSA}, 17.75%]), gram-negative bacilli (59.0% {Pseudomonas aeruginosa, 17.50%; Stenotrophomonas maltophilia, 6.75%; Acinetobacter species, 7.75%), and miscellaneous pathogens (9.0%). The infecting flora in nonventilated patients included gram-positive cocci (42.59% [OSSA, 13.33%; ORSA, 20.37%]), gram-negative bacilli (39.63% [P. aeruginosa, 9.26%; S. maltophilia, 1.11%; Acinetobacter species, 3.33%), and miscellaneous pathogens (17.78%).Conclusions.Our data demonstrated that patients with HAP, compared with those with VAP, had a similar frequency of infection with ORSA but less commonly had infections due to P. aeruginosa, Acinetobacter species, and S. maltophilia. However, the overall frequency of infection with these pathogens was sufficiently high to warrant the use of empirical therapy likely to be active against them. Our data supports using the currently recommended empirical therapy for both HAP and VAP.

scholarly journals Antimicrobial Activity of Ceftolozane–Tazobactam Tested against Contemporary (2012–2016) Enterobacteriaceae and Pseudomonas aeruginosa from ICU vs. non-ICU Isolates Collected in US Medical Centers

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S366-S366
Author(s):  
Dee Shortridge ◽  
Leonard R Duncan ◽  
Michael A Pfaller ◽  
Robert K Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
The United States ◽  
Icu Patients ◽  
Medical Centers ◽  
Hospital Acquired Pneumonia ◽  
Tract Infections ◽  
Abdominal Infections ◽  
Hospital Acquired ◽  
Lactamase Inhibitor ◽  
Research Grant

Abstract Background Ceftolozane-tazobactam (C-T) is a combination of a novel antipseudomonal cephalosporin and a well-described β-lactamase inhibitor. C-T was approved by the United States (US) Food and Drug Administration in 2014 for complicated urinary tract infections, including acute pyelonephritis and complicated intra-abdominal infections. C-T is currently in clinical trials for the treatment of hospital-acquired pneumonia. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance to gram-negative (GN) isolates worldwide. This study compares the activities of C-T and comparators against GN isolates from ICU patients and non-ICU patients. Methods A total of 3,100 GN ICU isolates and 3,271 isolates from non-ICU patients were collected from 30 US hospitals in 2012–2016. Isolates were tested for susceptibility (S) to C-T and comparators by CLSI broth microdilution methodology in a central monitoring laboratory. Other antibiotics tested included amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), meropenem (MER), and piperacillin-tazobactam (TZP). CLSI (2017) interpretive criteria were used for all except COL with Enterobacteriaceae (ENT), for which EUCAST (2017) criteria were used. Results The most common ENT species from ICU and non-ICU patients were similar. The 3 most common ENT for ICU and non-ICU isolates were Klebsiella pneumoniae, 24.1% and 25.8%; Escherichia coli, 19.4% and 18.2%; and Serratia marcescens, 14.7% and 14.3%, respectively. The most common non-enteric species was Pseudomonas aeruginosa (PSA) for ICU and non-ICU (72.7% and 78.2%). ICU ENT isolates generally had a lower %S than non-ICU (Table). ENT showed more variability than PSA for %S between ICU and non-ICU. Conclusion For ENT overall, MER and AMK were the most active, followed by C-T. Comparing ICU and non-ICU, MER and C-T were slightly more active vs. non-ICU ENT, while AMK %S was similar for both. For PSA, COL was the most active; C-T and AMK were similar. Activities between ICU and non-ICU isolates were similar for C-T and COL while AMK was more active vs. ICU isolates, and MER was more active vs. non-ICU. C-T showed potent activity against ICU and non-ICU isolates for ENT and PSA. Disclosures D. Shortridge, Merck: Research Contractor, Research grant; L. R. Duncan, Merck: Research Contractor, Research grant; M. A. Pfaller, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant

scholarly journals Activity of Meropenem-Vaborbactam against Bacterial Isolates Causing Pneumonia in Patients in U.S. Hospitals during 2014 to 2018

2020 ◽  
Vol 64 (3) ◽  
Author(s):  
Cecilia G. Carvalhaes ◽  
Dee Shortridge ◽  
Helio S. Sader ◽  
Mariana Castanheira
Keyword(s):  
Susceptibility Testing ◽  
The United States ◽  
Ventilator Associated Pneumonia ◽  
Bacterial Isolates ◽  
Content Type ◽  
Microdilution Method ◽  
Carbapenem Resistant ◽  
Broth Microdilution Method ◽  
Hospital Acquired Pneumonia ◽  
Hospital Acquired

ABSTRACT Meropenem-vaborbactam is approved to treat hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), in Europe. Meropenem-vaborbactam activity was evaluated against 3,193 Pseudomonas aeruginosa and 4,790 Enterobacterales isolates causing pneumonia, including VAP, in hospitalized patients in the United States. Susceptibility testing was performed by using the broth microdilution method, and all carbapenem-resistant isolates were submitted for whole-genome sequencing. Meropenem-vaborbactam exhibited almost complete activity against Enterobacterales (>99.9% susceptible), including carbapenem-resistant Enterobacterales (CRE), and was also very active against P. aeruginosa isolates (89.5% susceptible).

scholarly journals Ceftobiprole Activity against over 60,000 Clinical Bacterial Pathogens Isolated in Europe, Turkey, and Israel from 2005 to 2010

2014 ◽  
Vol 58 (7) ◽  
pp. 3882-3888 ◽  
Author(s):  
David J. Farrell ◽  
Robert K. Flamm ◽  
Helio S. Sader ◽  
Ronald N. Jones
Keyword(s):  
Antimicrobial Activity ◽  
High Activity ◽  
Wide Spectrum ◽  
Community Acquired Pneumonia ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Content Type ◽  
Hospital Acquired Pneumonia ◽  
Hospital Acquired

ABSTRACTCeftobiprole medocaril is a newly approved drug in Europe for the treatment of hospital-acquired pneumonia (HAP) (excluding patients with ventilator-associated pneumonia but including ventilated HAP patients) and community-acquired pneumonia in adults. The aim of this study was to evaluate thein vitroantimicrobial activity of ceftobiprole against prevalent Gram-positive and -negative pathogens isolated in Europe, Turkey, and Israel during 2005 through 2010. A total of 60,084 consecutive, nonduplicate isolates from a wide variety of infections were collected from 33 medical centers. Species identification was confirmed, and all isolates were susceptibility tested using reference broth microdilution methods. Ceftobiprole had high activity against methicillin-susceptibleStaphylococcus aureus(MSSA) (100.0% susceptible), methicillin-susceptible coagulase-negative staphylococci (CoNS), beta-hemolytic streptococci, andStreptococcus pneumoniae(99.3% susceptible), with MIC90values of 0.25, 0.12, ≤0.06, and 0.5 μg/ml, respectively. Ceftobiprole was active against methicillin-resistantS. aureus(MRSA) (98.3% susceptible) and methicillin-resistant CoNS, having a MIC90of 2 μg/ml. Ceftobiprole was active againstEnterococcus faecalis(MIC50/90, 0.5/4 μg/ml) but not against mostEnterococcus faeciumisolates. Ceftobiprole was very potent against the majority ofEnterobacteriaceae(87.3% susceptible), with >80% inhibited at ≤0.12 μg/ml. The potency of ceftobiprole againstPseudomonas aeruginosa(MIC50/90, 2/>8 μg/ml; 64.6% at MIC values of ≤4 μg/ml) was similar to that of ceftazidime (MIC50/90, 2/>16 μg/ml; 75.4% susceptible), but limited activity was observed againstAcinetobacterspp. andStenotrophomonas maltophilia. High activity was also observed against allHaemophilus influenzae(MIC90, ≤0.06 μg/ml) andMoraxella catarrhalis(MIC50/90, ≤0.06/0.25 μg/ml) isolates. Ceftobiprole demonstrated a wide spectrum of antimicrobial activity against this very large longitudinal sample of contemporary pathogens.

scholarly journals Ceftazidimeavibactam use in children and adolescents

2021 ◽  
Vol 23 (2) ◽  
pp. 173-183
Author(s):  
Оlga U. Stetsiouk ◽  
Irina V. Andreeva ◽  
А.U. Lekmanov ◽  
Еlena V. Haykina
Keyword(s):  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Pediatric Practice ◽  
Gram Negative ◽  
Hospital Acquired Pneumonia ◽  
Tract Infections ◽  
Hospital Acquired ◽  
Limited Choice ◽  
Intraabdominal Infections

Abstract The increasing number of infections caused by multidrug-resistant gram-negative bacteria in children is a serious problem all over the world. Ceftazidim-avibactam is a promising antimicrobial drug recently approved in Russia for use in pediatric practice. This review provides information on the possible use of ceftazidime-avibactam in children with complicated intraabdominal infections (in combination with metronidazole); complicated urinary tract infections, including pyelonephritis; hospital-acquired pneumonia, including ventilator-associated pneumonia; infections caused by aerobic gram-negative microorganisms in patients with limited choice of antibacterial therapy. Based on the data on the in vitro activity of the drug, the results of clinical studies of pharmacokinetics, safety and efficacy of ceftazidimeavibactam for the treatment of infections in children the main clinical cases in which the use of ceftazidimeavibactam in pediatric practice is most justified and appropriate are identified.

scholarly journals 1054. Activity of a Anti-staphylococcal Lysin, LSVT-1701: In vitro Susceptibility of Staphylococcus aureus and Coagulase-Negative Staphylococci (CoNS) Global Clinical Isolates (2002 to 2019)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S618-S619
Author(s):  
David Huang ◽  
Helio S Sader ◽  
Paul R Rhomberg ◽  
Katyna Borroto-Esoda ◽  
Eric Gaukel
Keyword(s):  
The United States ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Asia Pacific ◽  
In Vitro Activity ◽  
Coagulase Negative Staphylococci ◽  
Medical Centers ◽  
Broth Microdilution Method ◽  
Research Grant

Abstract Background LSVT-1701, formerly SAL200, is a novel, recombinantly-produced, bacteriophage-encoded lysin that specifically targets staphylococci via cell wall enzymatic hydrolysis. We reported the in vitro activity of LSVT-1701 against clinical isolates of S. aureus and coagulase-negative staphylococci (CoNS) collected worldwide. Methods LSVT-1701 and comparators were tested against 415 S. aureus (n=315) and CoNS (n=100) clinical isolates expressing various resistance phenotypes. The isolates were collected in 2002-2019 from medical centers located in the United States (50 medical centers; 174 isolates; 41.9% overall), Europe (37 medical centers; 140 isolates; 33.7% overall), Asia-Pacific region (15 medical centers; 55 isolates; 13.3% overall), and Latin America (12 medical centers; 46 isolates; 11.1% overall). These isolates originated mostly from the year 2019 (n=323).The isolates were susceptibility tested by the CLSI broth microdilution method. MIC interpretations were based on CLSI and EUCAST criteria where available. Results LSVT-1701 was highly active against S. aureus and CoNS isolates with MIC90 values of 2 mg/L for all S. aureus, methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and CoNS (Table). The highest LSVT-1701 MIC values were 4 and 8 mg/L among S. aureus and CoNS, respectively. LSVT-1701 retained potent activity against S. aureus isolates showing resistance or decreased susceptibility to oxacillin, vancomycin, teicoplanin, telavancin, linezolid, daptomycin, ceftaroline, or lefamulin; MIC50 values ranged from 0.5 to 1 mg/L and MIC90 values ranged from 1 to 4 mg/L among S. aureus resistant subsets. Summary of LSVT-1701 activity against S. aureus, CoNS and resistant subsets Conclusion LSVT-1701 demonstrated potent in vitro activity against contemporary clinical isolates of S. aureus and CoNS collected from medical centers worldwide and against resistant S. aureus isolates with uncommon resistance phenotypes. The results of this study support further clinical development of LSVT-1701 to treat staphylococcal infections. Disclosures David Huang, MD, PhD, Lysovant (Consultant) Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support, Contract no. HHSO100201600002C)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Paul R Rhomberg, Cidara Therapeutics, Inc. (Research Grant or Support)Pfizer, Inc. (Research Grant or Support) Katyna Borroto-Esoda, PhD, Lysovant (Consultant) Eric Gaukel, BS, Lysovant (Employee)

scholarly journals In Vitro Susceptibilities of Gram-Negative Bacteria Isolated from Hospitalized Patients in Four European Countries, Canada, and the United States in 2000-2001 to Expanded-Spectrum Cephalosporins and Comparator Antimicrobials: Implications for Therapy

2003 ◽  
Vol 47 (10) ◽  
pp. 3089-3098 ◽  
Author(s):  
Richard P. Wenzel ◽  
Daniel F. Sahm ◽  
Clyde Thornsberry ◽  
Deborah C. Draghi ◽  
Mark E. Jones ◽  
...  
Keyword(s):  
United States ◽  
Antimicrobial Agents ◽  
Klebsiella Oxytoca ◽  
Enterobacter Aerogenes ◽  
The United States ◽  
Hospitalized Patients ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Hospital Acquired

ABSTRACT Access to current antimicrobial agent surveillance data is an important prerequisite for the optimal management of patients with hospital-acquired infections. The present study used data collected in 2000 to 2001 from 670 laboratories in Europe (France, Germany, Italy, and Spain), Canada, and the United States to report on the in vitro activities of ceftriaxone, cefotaxime, and comparative agents against >125,000 isolates of gram-negative bacteria from hospitalized patients. All but two isolates of Enterobacteriaceae (one isolate of Proteus mirabilis from France and one isolate of Morganella morganii from Canada) were susceptible to imipenem. The susceptibility of Escherichia coli to ceftriaxone or cefotaxime was ≥97% in each country, and for P. mirabilis, susceptibility was 99% in each country except Italy. In contrast, susceptibility of E. coli to ciprofloxacin varied from 80.5% (Spain) to 94.0% (France); levofloxacin susceptibility ranged from 75.2% (Spain) to 91.6% (United States). Among Klebsiella pneumoniae and Klebsiella oxytoca isolates, ceftriaxone and cefotaxime susceptibilities ranged from 86.6 to 98.7% and 83.5 to 99.7%, respectively, depending upon the country. Considerable geographic variation in the susceptibilities (generally 85 to 95% susceptible) of Serratia marcescens and M. morganii to ceftriaxone and cefotaxime were observed. For S. marcescens, susceptibility to piperacillin-tazobactam varied from 81.5% (France) to 94.1% (Italy) and susceptibility to ciprofloxacin ranged from 66.2% (Germany) to 90.7% (Spain). Enterobacter cloacae and Enterobacter aerogenes were less susceptible to ceftriaxone and cefotaxime than were the other species of Enterobacteriaceae studied. The present study demonstrated that established parenteral expanded-spectrum cephalosporin antimicrobial agents retain significant in vitro activity against many clinically important gram-negative pathogens.

scholarly journals Current Rational to Prescribe Tigecycline: Critical Analysis of the Evidence and Usage Algorithms by an Argentinean Experts Panel

2009 ◽  
Vol 1 ◽  
pp. CMT.S3312
Author(s):  
Daniel Curcio ◽  
Laura I. Barcelona ◽  
Wanda Cornistein ◽  
Carlos Bantar ◽  
Laura Barcan ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
New Class ◽  
Complicated Skin ◽  
The Us ◽  
Hospital Acquired Pneumonia ◽  
Acinetobacter Spp ◽  
Gram Negative Organisms ◽  
Abdominal Infections ◽  
Hospital Acquired

Tigecycline is the first of a new class of antibiotics named glycylcyclines and is active in vitro against a variety of gram-positive and gram-negative organisms, including nosocomial resistant pathogens such as vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase-producing Enterobacteriaceae, and multidrug-resistant- Acinetobacter spp. This medication has been approved by the US Food and Drug Administration (FDA) for the treatment of complicated intra-abdominal infections (cIAI), complicated skin and skin structure infections (cSSSI) and community-acquired bacterial pneumonia. Tigecycline's pharmacological and microbiological profile has also encouraged physicians’ to use the drug in other infections caused by resistant pathogens featuring limited therapeutics options (i.e. hospital-acquired pneumonia-HAP). In this study we publish the conclusions of an expert panel that identify and evaluate the evidence to support the use of Tigecycline in hospitalized patients with one of the following three infections: cSSSI, cIAI and HAP, including ventilator-associated pneumonia. Based on this data the panel developed an Algorithm Rational to Prescribe Tigecycline (ART) for each pathology.

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