scholarly journals Pharmacodynamics of Fosfomycin: Insights into Clinical Use for Antimicrobial Resistance

2015 ◽  
Vol 59 (9) ◽  
pp. 5602-5610 ◽  
Author(s):  
F. Docobo-Pérez ◽  
G. L. Drusano ◽  
A. Johnson ◽  
J. Goodwin ◽  
S. Whalley ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Infection Model ◽  
Drug Resistant ◽  
Time Curve ◽  
Bacterial Killing ◽  
Unbound Fraction ◽  
Content Type ◽  
E Coli ◽  
Resistant Mutants ◽  
Tract Infections

ABSTRACTThe aim of this study was to improve the understanding of the pharmacokinetic-pharmacodynamic relationships of fosfomycin against extended-spectrum beta-lactamase (ESBL)-producingEscherichia colistrains that have different fosfomycin MICs. Our methods included the use of a hollow fiber infection model with three clinical ESBL-producingE. colistrains. Human fosfomycin pharmacokinetic profiles were simulated over 4 days. Preliminary studies conducted to determine the dose ranges, including the dose ranges that suppressed the development of drug-resistant mutants, were conducted with regimens from 12 g/day to 36 g/day. The combination of fosfomycin at 4 g every 8 h (q8h) and meropenem at 1 g/q8h was selected for further assessment. The total bacterial population and the resistant subpopulations were determined. No efficacy was observed against the Ec42444 strain (fosfomycin MIC, 64 mg/liter) at doses of 12, 24, or 36 g/day. All dosages induced at least initial bacterial killing against Ec46 (fosfomycin MIC, 1 mg/liter). High-level drug-resistant mutants appeared in this strain in response to 12, 15, and 18 g/day. In the study arms that included 24 g/day, once or in a divided dose, a complete extinction of the bacterial inoculum was observed. The combination of meropenem with fosfomycin was synergistic for bacterial killing and also suppressed all fosfomycin-resistant clones of Ec2974 (fosfomycin MIC, 1 mg/liter). We conclude that fosfomycin susceptibility breakpoints (≤64 mg/liter according to CLSI [forE. coliurinary tract infections only]) should be revised for the treatment of serious systemic infections. Fosfomycin can be used to treat infections caused by organisms that demonstrate lower MICs and lower bacterial densities, although relatively high daily dosages (i.e., 24 g/day) are required to prevent the emergence of bacterial resistance. The ratio of the area under the concentration-time curve for the free, unbound fraction of fosfomycin versus the MIC (fAUC/MIC) appears to be the dynamically linked index of suppression of bacterial resistance. Fosfomycin with meropenem can act synergistically againstE. colistrains in preventing the emergence of fosfomycin resistance.

scholarly journals In Vivo Bioluminescent Monitoring of Therapeutic Efficacy and Pharmacodynamic Target Assessment of Antofloxacin against Escherichia coli in a Neutropenic Murine Thigh Infection Model

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Yu-Feng Zhou ◽  
Meng-Ting Tao ◽  
Yu-Zhang He ◽  
Jian Sun ◽  
Ya-Hong Liu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Subcutaneous Administration ◽  
Free Drug ◽  
Infection Model ◽  
Bioluminescent Imaging ◽  
Time Curve ◽  
Content Type ◽  
E Coli ◽  
Tract Infections

ABSTRACT Antimicrobial resistance among uropathogens has increased the rates of infection-related morbidity and mortality. Antofloxacin is a novel fluoroquinolone with broad-spectrum antibacterial activity against urinary Gram-negative bacilli, such as Escherichia coli. This study monitored the in vivo efficacy of antofloxacin using bioluminescent imaging and determined pharmacokinetic (PK)/pharmacodynamic (PD) targets against E. coli isolates in a neutropenic murine thigh infection model. The PK properties were determined after subcutaneous administration of antofloxacin at 2.5, 10, 40, and 160 mg/kg of body weight. Following thigh infection, the mice were treated with 2-fold-increasing doses of antofloxacin from 2.5 to 80 mg/kg administered every 12 h. Efficacy was assessed by quantitative determination of the bacterial burdens in thigh homogenates and was compared with the bioluminescent density. Antofloxacin demonstrated both static and killing endpoints in relation to the initial burden against all study strains. The PK/PD index area under the concentration-time curve (AUC)/MIC correlated well with efficacy (R 2 = 0.92), and the dose-response relationship was relatively steep, as observed with escalating doses of antofloxacin. The mean free drug AUC/MIC targets necessary to produce net bacterial stasis and 1-log10 and 2-log10 kill for each isolate were 38.7, 66.1, and 147.0 h, respectively. In vivo bioluminescent imaging showed a rapid decrease in the bioluminescent density at free drug AUC/MIC exposures that exceeded the stasis targets. The integration of these PD targets combined with the results of PK studies with humans will be useful in setting optimal dosing regimens for the treatment of urinary tract infections due to E. coli.

scholarly journals Sequential Evolution of Vancomycin-Intermediate Resistance Alters Virulence in Staphylococcus aureus: Pharmacokinetic/Pharmacodynamic Targets for Vancomycin Exposure

2015 ◽  
Vol 60 (3) ◽  
pp. 1584-1591 ◽  
Author(s):  
Justin R. Lenhard ◽  
Tanya Brown ◽  
Michael J. Rybak ◽  
Calvin J. Meaney ◽  
Nicholas B. Norgard ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Galleria Mellonella ◽  
Infection Model ◽  
Bacterial Reduction ◽  
Accessory Gene ◽  
Time Curve ◽  
Bacterial Killing ◽  
Unbound Fraction ◽  
Content Type ◽  
Intermediate Resistance

Staphylococcus aureuspossesses exceptional virulence and a remarkable ability to adapt in the face of antibiotic therapy. We examined thein vitroevolution ofS. aureusin response to escalating vancomycin exposure by evaluating bacterial killing and the progression of resistance. A hollow-fiber infection model was utilized to simulate human doses of vancomycin increasing from 0.5 to 4 g every 12 h (q12h) versus a high inoculum (108CFU/ml) of methicillin-resistantS. aureus(MRSA) USA300 and USA400. Host-pathogen interactions usingGalleria mellonellaand accessory gene regulator (agr) expression were studied in serially obtained isolates. In both USA300 and USA400 MRSA isolates, vancomycin exposure up to 2 g q12h resulted in persistence and regrowth, whereas 4 g administered q12h achieved sustained killing against both strains. As vancomycin exposure increased from 0.5 to 2 g q12h, the bacterial population shifted toward vancomycin-intermediate resistance, and collateral increases in the MICs of daptomycin and televancin were observed over 10 days. Guideline-recommended exposure of a ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC/MIC ratio) of 200 displayed a 0.344-log bacterial reduction in area, whereasfAUC/MICs of 371 and 554 were needed to achieve 1.00- and 2.00-log reductions in area, respectively. The stepwise increase in resistance paralleled a decrease inG. mellonellamortality (P= 0.021) and a gradual decline of RNAIII expression over 10 days. Currently recommended doses of vancomycin resulted in amplification of resistance and collateral damage to other antibiotics. Decreases inagrexpression and virulence during therapy may be an adaptive mechanism ofS. aureuspersistence.

scholarly journals Meropenem Combined with Ciprofloxacin Combats Hypermutable Pseudomonas aeruginosa from Respiratory Infections of Cystic Fibrosis Patients

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Vanessa E. Rees ◽  
Rajbharan Yadav ◽  
Kate E. Rogers ◽  
Jürgen B. Bulitta ◽  
Veronika Wirth ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Time Course ◽  
Respiratory Infections ◽  
Resistant Bacteria ◽  
Infection Model ◽  
Time Curve ◽  
Bacterial Killing ◽  
Content Type ◽  
Concentration Time

ABSTRACT Hypermutable Pseudomonas aeruginosa organisms are prevalent in chronic respiratory infections and have been associated with reduced lung function in cystic fibrosis (CF); these isolates can become resistant to all antibiotics in monotherapy. This study aimed to evaluate the time course of bacterial killing and resistance of meropenem and ciprofloxacin in combination against hypermutable and nonhypermutable P. aeruginosa. Static concentration time-kill experiments over 72 h assessed meropenem and ciprofloxacin in mono- and combination therapies against PAO1 (nonhypermutable), PAOΔmutS (hypermutable), and hypermutable isolates CW8, CW35, and CW44 obtained from CF patients with chronic respiratory infections. Meropenem (1 or 2 g every 8 h [q8h] as 3-h infusions and 3 g/day as a continuous infusion) and ciprofloxacin (400 mg q8h as 1-h infusions) in monotherapies and combinations were further evaluated in an 8-day hollow-fiber infection model study (HFIM) against CW44. Concentration-time profiles in lung epithelial lining fluid reflecting the pharmacokinetics in CF patients were simulated and counts of total and resistant bacteria determined. All data were analyzed by mechanism-based modeling (MBM). In the HFIM, all monotherapies resulted in rapid regrowth with resistance at 48 h. The maximum daily doses of 6 g meropenem (T>MIC of 80% to 88%) and 1.2 g ciprofloxacin (area under the concentration-time curve over 24 h in the steady state divided by the MIC [AUC/MIC], 176), both given intermittently, in monotherapy failed to suppress regrowth and resulted in substantial emergence of resistance (≥7.6 log10 CFU/ml resistant populations). The combination of these regimens achieved synergistic killing and suppressed resistance. MBM with subpopulation and mechanistic synergy yielded unbiased and precise curve fits. Thus, the combination of 6 g/day meropenem plus ciprofloxacin holds promise for future clinical evaluation against infections by susceptible hypermutable P. aeruginosa.

scholarly journals Pharmacokinetics and Pharmacodynamics of Fosfomycin and Its Activity against Extended-Spectrum-β-Lactamase-, Plasmid-Mediated AmpC-, and Carbapenemase-ProducingEscherichia coliin a Murine Urinary Tract Infection Model

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Ilya Nikolaevich Zykov ◽  
Ørjan Samuelsen ◽  
Lotte Jakobsen ◽  
Lars Småbrekke ◽  
Dan I. Andersson ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Clinical Strain ◽  
Infection Model ◽  
Time Curve ◽  
Content Type ◽  
Tract Infections

ABSTRACTFosfomycin has become an attractive treatment alternative for urinary tract infections (UTIs) due to increasing multidrug resistance (MDR) inEscherichia coli. In this study, we evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) indices of fosfomycin and itsin vivoactivity in an experimental murine model of ascending UTI. Subcutaneous administration of fosfomycin showed that the mean peak plasma concentrations of fosfomycin were 36, 280, and 750 mg/liter following administration of a single dose of 0.75, 7.5, and 30 mg/mouse, respectively, with an elimination half-life of 28 min, and urine peak concentrations of 1,100, 33,400, and 70,000 mg/liter expected to be sustained above 1 mg/liter (MIC of the test strain, NU14) for 5, 8, and 9.5 h, respectively. The optimal PK/PD indices for reducing urine colony counts (number of CFU per milliliter) were determined to be the area under the concentration-time curve/MIC from 0 to 72 h and the maximum concentration/MIC on the basis of the dose-dependent bloodstream PK and the results of an evaluation of six dosing regimens. With a dosing regimen of 15 mg/mouse twice (every 36 h), fosfomycin significantly reduced the number of CFU per milliliter of all susceptible strains in urine, including clinical MDR strains, except for one clinical strain (P= 0.062). Variable degrees of reduction were observed in the bladder and kidneys. No significant reductions in the number of CFU per milliliter were observed with the resistant strains. In conclusion, fosfomycin shows concentration-dependentin vivoactivity, and the results suggest that fosfomycin is an effective alternative to carbapenems in treating MDRE. coliin uncomplicated UTIs. The data on the effectiveness of fosfomycin against the MDR isolates along with the results of PK/PD modeling should facilitate the further development of improved recommendations for its clinical use.

scholarly journals New Dosing Strategies for an Old Antibiotic: Pharmacodynamics of Front-Loaded Regimens of Colistin at Simulated Pharmacokinetics in Patients with Kidney or Liver Disease

2013 ◽  
Vol 58 (3) ◽  
pp. 1381-1388 ◽  
Author(s):  
Gauri G. Rao ◽  
Neang S. Ly ◽  
Curtis E. Haas ◽  
Samira Garonzik ◽  
Alan Forrest ◽  
...  
Keyword(s):  
Renal Failure ◽  
Viable Count ◽  
Infection Model ◽  
Combination Regimen ◽  
Time Curve ◽  
Bacterial Killing ◽  
Content Type ◽  
Dosing Regimens ◽  
The Impact

ABSTRACTIncreasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized anin vitropharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (108CFU/ml) ofPseudomonas aeruginosa. The pharmacokinetics were simulated for patients with hepatic (half-life [t1/2] of 3.2 h) or renal (t1/2of 14.8 h) disease. Front-loaded regimens (n= 5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve (fAUC) compared to those with traditional dosing regimens (n= 14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures (fAUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (fAUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log10within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum ofP. aeruginosa. The current study, which utilizes anin vitropharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections.

scholarly journals Efficacy of OH-CATH30 and Its Analogs against Drug-Resistant BacteriaIn Vitroand in Mouse Models

2012 ◽  
Vol 56 (6) ◽  
pp. 3309-3317 ◽  
Author(s):  
Sheng-An Li ◽  
Wen-Hui Lee ◽  
Yun Zhang
Keyword(s):  
Mouse Models ◽  
Bacterial Infections ◽  
Resistant Bacteria ◽  
Infection Model ◽  
Drug Resistant ◽  
Content Type ◽  
E Coli ◽  
Drug Resistant Bacteria

ABSTRACTAntimicrobial peptides (AMPs) have been considered alternatives to conventional antibiotics for drug-resistant bacterial infections. However, their comparatively high toxicity toward eukaryotic cells and poor efficacyin vivohamper their clinical application. OH-CATH30, a novel cathelicidin peptide deduced from the king cobra, possesses potent antibacterial activityin vitro. The objective of this study is to evaluate the efficacy of OH-CATH30 and its analog OH-CM6 against drug-resistant bacteriain vitroandin vivo. The MICs of OH-CATH30 and OH-CM6 ranged from 1.56 to 12.5 μg/ml against drug-resistant clinical isolates of several pathogenic species, includingEscherichia coli,Pseudomonas aeruginosa, and methicillin-resistantStaphylococcus aureus. The MICs of OH-CATH30 and OH-CM6 were slightly altered in the presence of 25% human serum. OH-CATH30 and OH-CM6 killedE. coliquickly (within 60 min) by disrupting the bacterial cytoplasmic membrane. Importantly, the 50% lethal doses (LD50) of OH-CATH30 and OH-CM6 in mice following intraperitoneal (i.p.) injection were 120 mg/kg of body weight and 100 mg/kg, respectively, and no death was observed at any dose up to 160 mg/kg following subcutaneous (s.c.) injection. Moreover, 10 mg/kg OH-CATH30 or OH-CM6 significantly decreased the bacterial counts as well as the inflammatory response in a mouse thigh infection model and rescued infected mice in a bacteremia model induced by drug-resistantE. coli. Taken together, our findings demonstrate that the natural cathelicidin peptide OH-CATH30 and its analogs exhibit relatively low toxicity and potent efficacy in mouse models, indicating that they may have therapeutic potential against the systemic infections caused by drug-resistant bacteria.

scholarly journals Pharmacokinetics and Pharmacodynamics of Nemonoxacin against Streptococcus pneumoniae in anIn VitroInfection Model

2013 ◽  
Vol 57 (7) ◽  
pp. 2942-2947 ◽  
Author(s):  
Wang Liang ◽  
Yuan-cheng Chen ◽  
Yu-ran Cao ◽  
Xiao-fang Liu ◽  
Jun Huang ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Drug Efficacy ◽  
Maximum Effect ◽  
Infection Model ◽  
Time Curve ◽  
Effect Analysis ◽  
Unbound Fraction ◽  
Content Type ◽  
Target Values

ABSTRACTThe aim of this paper was to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of nemonoxacin, a novel nonfluorinated quinolone, againstStreptococcus pneumoniaein vitro. A modified infection model was used to simulate the pharmacokinetics of nemonoxacin following scaling of single oral doses and multiple oral dosing. FourS. pneumoniaestrains with different penicillin sensitivities were selected, and the drug efficacy was quantified by the change in log colony counts within 24 h. A sigmoid maximum-effect (Emax) model was used to analyze the relationship between PK/PD parameters and drug effect. Analysis indicated that the killing pattern of nemonoxacin shows a dualism which is mainly concentration dependent when the MIC is low and that the better PK/PD index should be the area under the concentration-time curve for the free, unbound fraction of the drug divided by the MIC (fAUC0–24/MIC), which means that giving the total daily amount of drug as one dose is appropriate under those conditions. When the MIC is high, the time (T) dependency is important and the valid PK/PD index should be the cumulative percentage of a 24-h period in which the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (f%T>MIC), which means that to split the maximum daily dose into several separate doses will benefit the eradication of the bacteria. To obtain a 3-log10-unit decrease, the target values offAUC0–24/MIC andf%T>MIC are 47.05 and 53.4%, respectively.

scholarly journals Pharmacokinetics and pharmacodynamics of enrofloxacin treatment of Escherichia coli in a murine thigh infection modeling

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Xuesong Liu ◽  
Qingwen Yang ◽  
Yuying Fan ◽  
Yuanyi Du ◽  
Lei Lei ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Compartmental Analysis ◽  
Clinical Applications ◽  
Infection Model ◽  
Antibacterial Drug ◽  
Log10 Reduction ◽  
Time Curve ◽  
E Coli ◽  
Concentration Time ◽  
Target Values

Abstract Background Enrofloxacin is an antibacterial drug with broad-spectrum activity that is widely indicated for veterinary use. We aim to develop the clinical applications of Enrofloxacin against colibacillosis by using the neutropenic mice thigh infection model. Results The minimum inhibitory concentration (MIC) distribution of 67 isolated E. coli strains to ENR was calculated using CLSI guidelines. Whereas, the MIC50 value calculation was considered as the population PD parameter for ENR against E. coli strains. The MIC values of 15 E. coli strains were found to be nearest to the MIC50 i.e., 0.25 μg/mL. Of all the tested strains, the PK-PD and E. coli disease model was established via selected E. coli strain i.e., Heilong 15. We analyzed the PK characteristics of ENR and its metabolite ciprofloxacin (CIP) following a single subcutaneous (s.c.) injection of ENR (1.25, 2.5, 5, 10 mg/kg). The concentration-time profiling of ENR within the plasma specimens was determined by considering the non-compartmental analysis (NCA). The basic PK parameters of ENR for the peak drug concentration (Cmax) and the area under the concentration-time curve (AUC) values were found to be in the range of 0.27–1.97 μg/mL and 0.62–3.14 μg.h/mL, respectively. Multiple s.c. injection over 24 h (1.25, 2.5, 5, 10 mg/kg at various time points i.e., 6, 8, 12, and 24 h respectively) were administered to assess the targeted PD values. The Akaike Information Criterion (AIC) was used to choose PD models, and the model with the lowest AIC was chosen. The inhibitory Emax model was employed to calculate the related PK-PD parameters. The results of our study indicated that there was a strong correlation between the AUC/MIC and various antibacterial activities (R2 = 0.9928). The target values of dividing AUC/MIC by 24 h for bacteriostatic action were 1-log10 reduction, 2-log10 reduction, and 3-log10 reduction 0.325, 0.4375, 0.63, and 0.95 accordingly. Conclusion The identified pharmacodynamics targets for various antibacterial effects will be crucial in enhancing ENR clinical applications and serving as a key step in reducing bacterial resistance.

scholarly journals In Vivo Pharmacokinetic/Pharmacodynamic Targets of Levonadifloxacin against Staphylococcus aureus in a Neutropenic Murine Lung Infection Model

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Sachin S. Bhagwat ◽  
Hariharan Periasamy ◽  
Swapna S. Takalkar ◽  
Rajesh Chavan ◽  
Pavan Tayde ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Lung Infection ◽  
Infection Model ◽  
Phase 3 ◽  
Time Curve ◽  
Unbound Fraction ◽  
Content Type ◽  
Murine Lung ◽  
Selection Of

ABSTRACT Levonadifloxacin is a novel benzoquinolizine subclass of fluoroquinolone, active against quinolone-resistant Staphylococcus aureus. A phase 3 trial for levonadifloxacin and its oral prodrug was recently completed. The present study identified area under the concentration-time curve for the free, unbound fraction of a drug divided by the MIC (fAUC/MIC) as an efficacy determinant for levonadifloxacin in a neutropenic murine lung infection model. Mean plasma fAUC/MIC requirement for static and 1 log10 kill effects against 9 S. aureus were 8.1 ± 6.0 and 25.8 ± 12.3, respectively. These targets were employed in the selection of phase 3 doses.

scholarly journals Implications of Foraging and Interspecies Interactions of Birds for Carriage of Escherichia coli Strains Resistant to Critically Important Antimicrobials

2020 ◽  
Vol 86 (20) ◽  
Author(s):  
Shewli Mukerji ◽  
Samantha Gunasekera ◽  
James Nicholas Dunlop ◽  
Marc Stegger ◽  
David Jordan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bird Species ◽  
Mobile Genetic Elements ◽  
Food Sources ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
E Coli ◽  
Genetic Elements ◽  
Tract Infections

ABSTRACT Globally, gulls have been associated with carriage of high levels of Escherichia coli strains resistant to critically important antimicrobials (CIAs), a major concern, as these antimicrobials are the sole alternative or one among only a few alternatives available to treat severe life-threatening infections in humans. Previous studies of Australian silver gulls demonstrated high levels of resistance to CIAs, particularly fluoroquinolone and extended-spectrum cephalosporins, among E. coli strains (carriage at 24% and 22%, respectively). This study aimed to identify and characterize strains from four distinct bird species inhabiting a common coastal environment, determine the frequency of carriage of CIA-resistant E. coli strains, and examine if these resistant clones and their resistance-encoding mobile genetic elements (MGEs) could be transmitted between species. CIA-resistant E. coli was detected in silver gulls (53%), little penguins (11%), and feral pigeons (10%), but not in bridled terns. In total, 37 different sequence types (STs) were identified, including clinically significant human-associated lineages, such as ST131, ST95, ST648, ST69, ST540, ST93, ST450, and ST10. Five main mobile genetic elements associated with blaCTX-M-positive E. coli strains isolated from three bird species were detected. Examination of clonal lineages and MGEs provided indirect evidence of transfer of resistance between bird species. The carriage of CIA-resistant E. coli by gulls and pigeons with proximity to humans, and in some instances food-producing animals, increases the likelihood of further bidirectional dissemination. IMPORTANCE It has been shown that 20% of Australian silver gulls carry drug-resistant Escherichia coli strains of anthropogenic origin associated with severe diseases, such as sepsis and urinary tract infections, in humans. To further characterize the dynamics of drug-resistant E. coli in wildlife populations, we investigated the carriage of critically important antimicrobial (CIA) drug-resistant E. coli in four bird species in a common environment. Our results indicated that gulls, pigeons, and penguins carried drug-resistant E. coli strains, and analysis of mobile genetic elements associated with resistance genes indicated interspecies resistance transfer. Terns, representing a bird species that forages on natural food sources at sea and distant from humans, did not test positive for drug-resistant E. coli. This study demonstrates carriage of CIA-resistant bacteria in multiple bird species living in areas commonly inhabited by humans and provides further evidence for a leapfrog effect of resistance in wildlife, facilitated by feeding habits.

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