scholarly journals In VitroSpectrum of Pexiganan Activity When Tested against Pathogens from Diabetic Foot Infections and with Selected Resistance Mechanisms

2015 ◽  
Vol 59 (3) ◽  
pp. 1751-1754 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Katie M. Simpson ◽  
David J. Farrell ◽  
Helio S. Sader ◽  
...  
Keyword(s):  
Diabetic Foot ◽  
Antimicrobial Agents ◽  
Resistance Mechanisms ◽  
Surveillance Program ◽  
Content Type ◽  
Diabetic Foot Infections ◽  
Antimicrobial Surveillance ◽  
Mueller Hinton ◽  
The Family ◽  
Infection Types

ABSTRACTPexiganan, a 22-amino-acid synthetic cationic peptide, is currently in phase 3 clinical trials as a topical antimicrobial agent for the treatment of mild infections associated with diabetic foot ulcers. Bacterial isolates from the 2013 SENTRY Antimicrobial Surveillance Program designated as pathogens from diabetic foot infections (DFI) and Gram-negative and -positive pathogens from various infection types that harbored selected resistance mechanisms/phenotypes were tested against pexiganan in reference cation-adjusted Mueller-Hinton broth. The MIC50and MIC90against all organisms tested from DFI were 16 and 32 μg/ml, respectively.Escherichia coli,Klebsiella pneumoniae,Citrobacter koseri,Enterobacter cloacae,Acinetobacterspecies, andPseudomonas aeruginosaMIC values ranged from 8 to 16 μg/ml. Pexiganan MIC values amongStaphylococcus aureus(methicillin-resistantS. aureus[MRSA] and methicillin-susceptibleS. aureus[MSSA]), beta-hemolytic streptococci, andEnterococcus faeciumranged from 8 to 32 μg/ml. Pexiganan activity was not adversely affected for members of the familyEnterobacteriaceaeorP. aeruginosathat produced β-lactamases or resistance mechanisms to other commonly used antimicrobial agents. Decreased susceptibility to vancomycin did not affect pexiganan activity againstS. aureusorE. faecium.Enterococcus faecalisappears to be intrinsically less susceptible to pexiganan (MIC, 32 to 256 μg/ml). The “all organism” MIC90of 32 μg/ml for pexiganan in this study was >250-fold below the pexiganan concentration in the cream/delivery vehicle being developed for topical use.

scholarly journals 1593. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against OXA-48 β-lactamase–Producing Enterobacterales Collected in International Medical Centers, Including the United States, in 2017–2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S793-S793
Author(s):  
Lynn-Yao Lin ◽  
Dmitri Debabov ◽  
William Chang
Keyword(s):  
Antimicrobial Agents ◽  
The United States ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Surveillance Program ◽  
Multiple Resistance ◽  
In Vitro Susceptibility ◽  
Medical Centers ◽  
Custom Made

Abstract Background OXA-48 is a carbapenemase with low-level hydrolytic activity toward cephalosporins. This study evaluated in vitro activities of ceftazidime-avibactam (CAZ-AVI), meropenem (MEM), meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T), and other antimicrobial agents against 113 OXA-48-producing Enterobacterales with multiple resistance mechanisms collected in a 2017–2018 global surveillance program. Methods Nonduplicate clinical isolates of 113 Enterobacterales were collected from medical centers in 25 countries in 2017–2018. In vitro susceptibility tests were performed by broth microdilution with a custom-made panel consisting of CAZ-AVI, ceftazidime (CAZ), MEM, MVB, C/T, colistin (COL), gentamicin (GEN), levofloxacin (LEV), and amikacin (AMK). Whole genome sequencing or quantitative PCR data were used to analyze resistance mechanisms, such as OXA-48, extended-spectrum β-lactamase (ESBL), original-spectrum β-lactamase (OSBL), and AmpC β-lactamase. Clinical and Laboratory Standards Institute breakpoints were applied for susceptibility interpretations. Results Of 113 OXA-48–producing clinical isolates, 20 carried OXA-48 alone. The remaining 93 isolates carried additional β-lactamases, including 63 with ESBL (CTX-M-15) + OSBL (SHV, TEM), 15 with AmpC (DHA, AAC, CMY) + ESBL (CTX-M-15), and 15 with OSBL (SHV, TEM). 99.1% (all but 1) of all isolates tested were susceptible to CAZ-AVI, whereas 71.7%, 17.7%, and 14.2% were susceptible to MVB, MEM, and C/T, respectively. Among isolates harboring multiple resistance mechanisms (OXA-48 + ESBL + OSBL; n=63), 98.4%, 69.8%, 11.1%, and 7.9% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively. Among isolates carrying OXA-48 + AmpC + ESBL + OSBL (n=15), 100%, 66.7%, 13.3%, and 13.3% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively (Table). Aminoglycosides (AMK and GEN) and other β-lactams (eg, CAZ) were 20%–90% active against these isolates. COL was the second most effective comparator, inhibiting 83.2% of these isolates. Table Conclusion CAZ-AVI was the most effective agent in this study compared with other antibiotics, including β-lactams, β-lactam–β-lactamase inhibitor combinations, aminoglycosides, and COL, against OXA-48-producing Enterobacterales carrying multiple β-lactamases. Disclosures Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee)

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

scholarly journals Summary of Linezolid Activity and Resistance Mechanisms Detected during the 2012 LEADER Surveillance Program for the United States

2013 ◽  
Vol 58 (2) ◽  
pp. 1243-1247 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Robert K. Flamm ◽  
Patricia A. Hogan ◽  
James E. Ross ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Susceptibility Testing ◽  
The United States ◽  
Resistance Mechanisms ◽  
Regulatory Approval ◽  
Surveillance Program ◽  
Gram Positive ◽  
Content Type

ABSTRACTThis study summarizes the linezolid susceptibility testing results for 7,429 Gram-positive pathogens from 60 U.S. sites collected during the 2012 sampling year for the LEADER Program. Linezolid showed potent activity when tested against 2,980Staphylococcus aureusisolates, inhibiting all but 3 at ≤2 μg/ml. Similarly, linezolid showed coverage against 99.5% of enterococci, as well as for all streptococci tested. These results confirm a long record of linezolid activity against U.S. Gram-positive isolates since regulatory approval in 2000.

scholarly journals Experimental Induction of Bacterial Resistance to the Antimicrobial Peptide Tachyplesin I and Investigation of the Resistance Mechanisms

2016 ◽  
Vol 60 (10) ◽  
pp. 6067-6075 ◽  
Author(s):  
Jun Hong ◽  
Jianye Hu ◽  
Fei Ke
Keyword(s):  
Antimicrobial Peptide ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Resistance Mechanisms ◽  
Cross Resistance ◽  
Antibacterial Drug ◽  
Cationic Antimicrobial Peptide ◽  
Content Type ◽  
Tachyplesin I

ABSTRACTTachyplesin I is a 17-amino-acid cationic antimicrobial peptide (AMP) with a typical cyclic antiparallel β-sheet structure that is a promising therapeutic for infections, tumors, and viruses. To date, no bacterial resistance to tachyplesin I has been reported. To explore the safety of tachyplesin I as an antibacterial drug for wide clinical application, we experimentally induced bacterial resistance to tachyplesin I by using two selection procedures and studied the preliminary resistance mechanisms.Aeromonas hydrophilaXS91-4-1,Pseudomonas aeruginosaCGMCC1.2620, andEscherichia coliATCC 25922 and F41 showed resistance to tachyplesin I under long-term selection pressure with continuously increasing concentrations of tachyplesin I. In addition,P. aeruginosaandE. coliexhibited resistance to tachyplesin I under UV mutagenesis selection conditions. Cell growth and colony morphology were slightly different between control strains and strains with induced resistance. Cross-resistance to tachyplesin I and antimicrobial agents (cefoperazone and amikacin) or other AMPs (pexiganan, tachyplesin III, and polyphemusin I) was observed in some resistant mutants. Previous studies showed that extracellular protease-mediated degradation of AMPs induced bacterial resistance to AMPs. Our results indicated that the resistance mechanism ofP. aeruginosawas not entirely dependent on extracellular proteolytic degradation of tachyplesin I; however, tachyplesin I could induce increased proteolytic activity inP. aeruginosa. Most importantly, our findings raise serious concerns about the long-term risks associated with the development and clinical use of tachyplesin I.

OP67 Bacteriology of diabetic foot infections and susceptibility to antimicrobial agents in Cameroon

2014 ◽  
Vol 103 ◽  
pp. S27 ◽  
Author(s):  
M. Dehayem ◽  
E. Ngassam ◽  
F. Mendane ◽  
V. Balla ◽  
J. Saji ◽  
...  
Keyword(s):  
Diabetic Foot ◽  
Antimicrobial Agents ◽  
Diabetic Foot Infections

scholarly journals Surveillance of Omadacycline Activity Tested against Clinical Isolates from the United States and Europe as Part of the 2016 SENTRY Antimicrobial Surveillance Program

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Michael A. Pfaller ◽  
Michael D. Huband ◽  
Dee Shortridge ◽  
Robert K. Flamm
Keyword(s):  
United States ◽  
Moraxella Catarrhalis ◽  
The United States ◽  
Surveillance Program ◽  
Bacterial Isolates ◽  
Content Type ◽  
Medical Centers ◽  
Antimicrobial Surveillance ◽  
Serious Infections ◽  
Viridans Group Streptococci

ABSTRACTOmadacycline was tested against 21,000 bacterial isolates collected prospectively from medical centers in Europe and the United States during 2016. Omadacycline was active againstStaphylococcus aureus(MIC50/MIC90, 0.12/0.25 mg/liter), including methicillin-resistantS. aureus(MRSA); streptococci (MIC50/MIC90, 0.06/0.12 mg/liter), includingStreptococcus pneumoniae, viridans group streptococci, and beta-hemolytic streptococci;Enterobacteriaceae, includingEscherichia coli(MIC50/MIC90, 0.5/2 mg/liter);Haemophilus influenzae(MIC50/MIC90, 1/1 mg/liter); andMoraxella catarrhalis(MIC50/MIC90, 0.25/0.25 mg/liter). Omadacycline merits further study in serious infections where resistant pathogens may be encountered.

scholarly journals The Microbiology of Bloodstream Infection: 20-Year Trends from the SENTRY Antimicrobial Surveillance Program

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Daniel J. Diekema ◽  
Po-Ren Hsueh ◽  
Rodrigo E. Mendes ◽  
Michael A. Pfaller ◽  
Kenneth V. Rolston ◽  
...  
Keyword(s):  
Bloodstream Infection ◽  
Acinetobacter Calcoaceticus ◽  
Multidrug Resistant ◽  
Geographic Region ◽  
Surveillance Program ◽  
Surveillance Period ◽  
Content Type ◽  
E Coli ◽  
Medical Centers ◽  
Antimicrobial Surveillance

ABSTRACT Bloodstream infection (BSI) organisms were consecutively collected from >200 medical centers in 45 nations between 1997 and 2016. Species identification and susceptibility testing followed Clinical and Laboratory Standards Institute broth microdilution methods at a central laboratory. Clinical data and isolates from 264,901 BSI episodes were collected. The most common pathogen overall was Staphylococcus aureus (20.7%), followed by Escherichia coli (20.5%), Klebsiella pneumoniae (7.7%), Pseudomonas aeruginosa (5.3%), and Enterococcus faecalis (5.2%). S. aureus was the most frequently isolated pathogen overall in the 1997-to-2004 period, but E. coli was the most common after 2005. Pathogen frequency varied by geographic region, hospital-onset or community-onset status, and patient age. The prevalence of S. aureus isolates resistant to oxacillin (ORSA) increased until 2005 to 2008 and then declined among hospital-onset and community-acquired BSI in all regions. The prevalence of vancomycin-resistant enterococci (VRE) was stable after 2012 (16.4% overall). Daptomycin resistance among S. aureus and enterococci (DRE) remained rare (<0.1%). In contrast, the prevalence of multidrug-resistant (MDR) Enterobacteriaceae increased from 6.2% in 1997 to 2000 to 15.8% in 2013 to 2016. MDR rates were highest among nonfermentative Gram-negative bacilli (GNB), and colistin was the only agent with predictable activity against Acinetobacter baumannii-Acinetobacter calcoaceticus complex (97% susceptible). In conclusion, S. aureus and E. coli were the predominant causes of BSI worldwide during this 20-year surveillance period. Important resistant phenotypes among Gram-positive pathogens (MRSA, VRE, or DRE) were stable or declining, whereas the prevalence of MDR-GNB increased continuously during the monitored period. MDR-GNB represent the greatest therapeutic challenge among common bacterial BSI pathogens.

scholarly journals PRESCRIPTION PATTERN AND USAGE OF ANTIMICROBIAL AGENTS FOR TREATING DIABETIC FOOT INFECTIONS AT TERTIARY CARE CENTRE

2020 ◽  
pp. 136-141
Author(s):  
DASARAJU RAJESH ◽  
M. V. ADVAITHA ◽  
RAJENDRA HOLLA
Keyword(s):  
Diabetic Foot ◽  
Antimicrobial Agents ◽  
Tertiary Care ◽  
Local Treatment ◽  
Tertiary Care Centre ◽  
Prescribing Pattern ◽  
Anaerobic Microorganisms ◽  
Diabetic Foot Infections ◽  
Gram Negative Organisms ◽  
Treatment Of Wounds

Objective: Due to the uncertainty about optimal antibiotic treatment, and probably substantial variation in practice, the present study was carried out to determine the bacterial profiles of infected diabetic foot ulcers (DFUs) and also to analyze the prescribing pattern of antibiotics used. Methods: A prospective observational study was carried out in the department of General surgery at a tertiary care teaching hospital, Mangalore. Demographic details and treatment data of 78 patients were collected in a specially designed Proforma, and the data were analyzed using Microsoft Excel. Results: According to Meggit-Wagner's classification, patients admitted with DFUs predominantly belonged to WAGNER 1 category (36%), followed by WAGNER 4 (26%) and WAGNER 2 (22%) categories. Out of 66 culture-positive specimens, 21 (31.8%) had monomicrobial flora, and 45 (68.2%) had polymicrobial flora. A total of 148 organisms were obtained from the specimens. The most common isolates were Staphylococcus aureus (22.3%) and Pseudomonas aeruginosa (17.5%). Ceftriaxone was the most commonly prescribed empirical antibiotic (29%), followed by linezolid (20%), piperacillin-tazobactam (20%), amoxicillin-clavulanic acid (13%), cefoperazone-sulbactam (11%). After the culture and sensitivity (C/S) results, antimicrobials were changed in 74.61% of patients in the preference of Linezolid (51%), Amikacin (27%), Levofloxacin (19%), Ciprofloxacin (17%), Piperacillin-tazobactam (13%), Cefixime (15%), Ceftriaxone (11%) among others. Clindamycin and metronidazole were used to cover anaerobic microorganisms. Conclusion: Most of the microorganisms isolated from DFUs were resistant to many types of antibiotics. Gram-positive organisms were largely sensitive to linezolid and vancomycin, while Gram-negative organisms to amikacin and imipenem. Local treatment of wounds is essential.

scholarly journals Utility of Methicillin-Resistant Staphylococcus aureus Nares Screening for Patients with a Diabetic Foot Infection

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Kari A. Mergenhagen ◽  
Michael Croix ◽  
Kaitlyn E. Starr ◽  
John A. Sellick ◽  
Alan J. Lesse
Keyword(s):  
Staphylococcus Aureus ◽  
Diabetic Foot ◽  
International Classification Of Diseases ◽  
Methicillin Resistant ◽  
Content Type ◽  
Diabetic Foot Infection ◽  
Entire Cohort ◽  
Diabetic Foot Infections ◽  
Medical Centers ◽  
Classification Of Diseases

ABSTRACT Treatment of suspected methicillin-resistant Staphylococcus aureus (MRSA) is a cornerstone of severe diabetic foot infections; however, antibiotics can be associated with toxicity. The objective of this study was to determine the negative predictive value (NPV) of MRSA nares screening in the determination of subsequent MRSA in patients with a diabetic foot infection. This was a retrospective cohort study across Veterans Affairs (VA) medical centers from 1 January 2007 to 1 January 2018. Data from patients with an International Classification of Diseases (ICD) code for a diabetic foot infection with MRSA nares screening, and subsequent cultures were evaluated for the presence of MRSA. NPVs were calculated for the entire cohort, as well as for a subgroup representing deep cultures. Additionally, the distribution of all pathogens isolated from diabetic foot infections was determined. A total of 8,163 episodes were included in the analysis for NPV. The NPV of MRSA nares screening for MRSA diabetic foot infection was 89.6%. For the deep cultures, the NPV was 89.2%. The NPV for cultures originating from the foot was 89.7%, and the NPV for those originating from the toe was 89.4%. There were 17,822 pathogens isolated from the diabetic foot cultures. MRSA was isolated in 7.5% of cultures, and methicillin-susceptible S. aureus was isolated in 24.8%. Enterococcus was identified in 14.7% of cultures, Proteus in 7.3%, and Pseudomonas in 6.8% of cultures. Given the high NPVs, the use of MRSA nares screening may be appropriate as a stewardship tool for deescalation and avoidance of empirical anti-MRSA therapy in patients who are not nasal carries of MRSA.

Sign in / Sign up

Export Citation Format

Share Document