Antibiotic Resistance in Pseudomonas aeruginosa Related to Quinolone Formulary Changes: An Interrupted Time Series Analysis

Pseudomonas aeruginosa is a nosocomial pathogen capable of exhibiting a variety of resistance mechanisms against multiple classes of antibiotics. Fluoroquinolones, commonly used to treat a variety of infections in both ambulatory and hospitalized patients, have been increasingly linked to the development of resistance, both to fluoroquinolones and to other classes of antibiotics including β-lactams, cephalosporins, and carbapenems. In turn, as many as 95% of multidrug-resistant pseudomonal isolates may be resistant to fluoroquinolones. Although research has examined the effect of fluoroquinolone use on P. aeruginosa resistance, to our knowledge, no work has been published describing possible differences among individual fluoroquinolones related to resistance to other antibiotic classes. The purpose of this analysis was to assess the possible effects of varying usage of levofloxacin, gatifloxacin, and moxifloxacin on P. aeruginosa susceptibility to piperacillin-tazobactam, cefepime, and tobramycin. Data from January 2000 through December 2008 were obtained from clinical microbiology and pharmacy databases of the Medical University of South Carolina Medical Center, which is a 689-bed academic medical center and level 1 trauma center with adult and pediatric beds. This study was approved by the institution's institutional review board.

Download Full-text

The impact of formulary restriction on the relative consumption of carbapenems in intensive care units at an academic medical center

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2019.170 ◽

2019 ◽

Vol 40 (9) ◽

pp. 1056-1058

Author(s):

Jacob W. Pierce ◽

Andrew Kirk ◽

Kimberly B. Lee ◽

John D. Markley ◽

Amy Pakyz ◽

...

Keyword(s):

Intensive Care ◽

Intensive Care Units ◽

Medical Center ◽

Academic Medical Center ◽

Interrupted Time Series ◽

Interrupted Time Series Analysis ◽

Surgical Intensive Care ◽

Academic Medical ◽

The Impact ◽

Formulary Restriction

AbstractAntipseudomonal carbapenems are an important target for antimicrobial stewardship programs. We evaluated the impact of formulary restriction and preauthorization on relative carbapenem use for medical and surgical intensive care units at a large, urban academic medical center using interrupted time-series analysis.

Download Full-text

Decreased Resistance of Pseudomonas aeruginosa with Restriction of Ciprofloxacin in a Large Teaching Hospital's Intensive Care and Intermediate Care Units

Infection Control and Hospital Epidemiology ◽

10.1086/664763 ◽

2012 ◽

Vol 33 (4) ◽

pp. 368-373 ◽

Cited By ~ 33

Author(s):

G. Jonathan Lewis ◽

Xiangming Fang ◽

Michael Gooch ◽

Paul P. Cook

Keyword(s):

Time Series ◽

Pseudomonas Aeruginosa ◽

Intensive Care ◽

Time Series Analysis ◽

Tertiary Care ◽

Interrupted Time Series ◽

Multidrug Resistant ◽

Intermediate Care ◽

Interrupted Time Series Analysis ◽

Gram Negative

Objective.To examine the effect of restricting ciprofloxacin on the resistance of nosocomial gram-negative bacilli, including Pseudomonas aeruginosa, to antipseudomonal carbapenems.Design.Interrupted time-series analysis.Setting.Tertiary care teaching hospital with 11 intensive care and intermediate care units with a total of 295 beds.Patients.All nosocomial isolates of P. aeruginosa.Intervention.Restriction of ciprofloxacin.Results.There was a significant decreasing trend observed in the percentage (P = .0351) and the rate (P = .0006) of isolates of P. aeruginosa that were resistant to antipseudomonal carbapenems following the restriction of ciprofloxacin. There was also a significant decreasing trend observed in the percentage (P = .0017) and the rate (P = .0001) of isolates of ciprofloxacin-resistant P. aeruginosa. The rate of cefepime-resistant P. aeruginosa isolates declined (P = .004 ) but the percentage of cefepime-resistant P. aeruginosa isolates did not change. There were no significant changes observed in the rate or the percentage of piperacillin-tazobactam-resistant P. aeruginosa isolates. There were no significant changes observed in the susceptibilities of nosocomial Enterobacteriaciae or Acinetobacter baumannii isolates that were resistant to carbapenems. Over the study period there was a significant increase in the use of carbapenems (P = .0134); the use of ciprofloxacin decreased significantly (P = .0027). There were no significant changes in the use of piperacillin-tazobactam or cefepime.Conclusion.Restriction of ciprofloxacin was associated with a decreased resistance of P. aeruginosa isolates to antipseudomonal carbapenems and ciprofloxacin in our hospital's intermediate care and intensive care units. There were no changes observed in the susceptibilities of nosocomial Enterobacteriaciae or A. baumannii to carbapenems, despite increased carbapenem use. Reducing ciprofloxacin use may be a means of controlling multidrug-resistant P. aeruginosa.

Download Full-text

Chasing the rate: An interrupted time series analysis of interventions targeting reported hospital onset Clostridioides difficile, 2013–2018

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.247 ◽

2020 ◽

Vol 41 (10) ◽

pp. 1142-1147

Author(s):

Michelle E. Doll ◽

Jinlei Zhao ◽

Le Kang ◽

Barry Rittmann ◽

Michael Alvarez ◽

...

Keyword(s):

Time Series ◽

Decision Support ◽

Infection Control ◽

Medical Center ◽

Academic Medical Center ◽

Interrupted Time Series ◽

Interrupted Time Series Analysis ◽

Test Volume ◽

Clostridioides Difficile ◽

The Impact

AbstractObjective:To assess the impact of major interventions targeting infection control and diagnostic stewardship in efforts to decrease Clostridioides difficile hospital onset rates over a 6-year period.Design:Interrupted time series.Setting:The study was conducted in an 865-bed academic medical center.Methods:Monthly hospital-onset C. difficile infection (HO-CDI) rates from January 2013 through January 2019 were analyzed around 5 major interventions: (1) a 2-step cleaning process in which an initial quaternary ammonium product was followed with 10% bleach for daily and terminal cleaning of rooms of patients who have tested positive for C. difficile (February 2014), (2) UV-C device for all terminal cleaning of rooms of C. difficile patients (August 2015), (3) “contact plus” isolation precautions (June 2016), (4) sporicidal peroxyacetic acid and hydrogen peroxide cleaning in all patient areas (June 2017), (5) electronic medical record (EMR) decision support tool to facilitate appropriate C. difficile test ordering (March 2018).Results:Environmental cleaning interventions and enhanced “contact plus” isolation did not impact HO-CDI rates. Diagnostic stewardship via EMR decision support decreased the HO-CDI rate by 6.7 per 10,000 patient days (P = .0079). When adjusting rates for test volume, the EMR decision support significance was reduced to a difference of 5.1 case reductions per 10,000 patient days (P = .0470).Conclusion:Multiple aggressively implemented infection control interventions targeting CDI demonstrated a disappointing impact on endemic CDI rates over 6 years. This study adds to existing data that outside of an outbreak situation, traditional infection control guidance for CDI prevention has little impact on endemic rates.

Download Full-text

Impact of Discontinuing Contact Precautions for Methicillin-ResistantStaphylococcus aureusand Vancomycin-ResistantEnterococcus: An Interrupted Time Series Analysis

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2018.57 ◽

2018 ◽

Vol 39 (6) ◽

pp. 676-682 ◽

Cited By ~ 20

Author(s):

Gonzalo Bearman ◽

Salma Abbas ◽

Nadia Masroor ◽

Kakotan Sanogo ◽

Ginger Vanhoozer ◽

...

Keyword(s):

Time Series ◽

Infection Prevention ◽

Urinary Catheter ◽

Medical Center ◽

Academic Medical Center ◽

Interrupted Time Series ◽

Infection Rates ◽

Interrupted Time Series Analysis ◽

Contact Precautions ◽

The Impact

OBJECTIVETo investigate the impact of discontinuing contact precautions among patients infected or colonized with methicillin-resistantStaphylococcus aureus(MRSA) or vancomycin-resistantEnterococcus(VRE) on rates of healthcare-associated infection (HAI). DESIGN. Single-center, quasi-experimental study conducted between 2011 and 2016.METHODSWe employed an interrupted time series design to evaluate the impact of 7 horizontal infection prevention interventions across intensive care units (ICUs) and hospital wards at an 865-bed urban, academic medical center. These interventions included (1) implementation of a urinary catheter bundle in January 2011, (2) chlorhexidine gluconate (CHG) perineal care outside ICUs in June 2011, (3) hospital-wide CHG bathing outside of ICUs in March 2012, (4) discontinuation of contact precautions in April 2013 for MRSA and VRE, (5) assessments and feedback with bare below the elbows (BBE) and contact precautions in August 2014, (6) implementation of an ultraviolet-C disinfection robot in March 2015, and (7) 72-hour automatic urinary catheter discontinuation orders in March 2016. Segmented regression modeling was performed to assess the changes in the infection rates attributable to the interventions.RESULTSThe rate of HAI declined throughout the study period. Infection rates for MRSA and VRE decreased by 1.31 (P=.76) and 6.25 (P=.21) per 100,000 patient days, respectively, and the infection rate decreased by 2.44 per 10,000 patient days (P=.23) for device-associated HAI following discontinuation of contact precautions.CONCLUSIONThe discontinuation of contact precautions for patients infected or colonized with MRSA or VRE, when combined with horizontal infection prevention measures was not associated with an increased incidence of MRSA and VRE device-associated infections. This approach may represent a safe and cost-effective strategy for managing these patients.Infect Control Hosp Epidemiol2018;39:676–682

Download Full-text

Development of Resistance in Wild-Type and Hypermutable Pseudomonas aeruginosa Strains Exposed to Clinical Pharmacokinetic Profiles of Meropenem and Ceftazidime Simulated In Vitro

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00160-07 ◽

2007 ◽

Vol 51 (10) ◽

pp. 3642-3649 ◽

Cited By ~ 19

Author(s):

Beate Henrichfreise ◽

Irith Wiegand ◽

Ingeborg Luhmer-Becker ◽

Bernd Wiedemann

Keyword(s):

Pseudomonas Aeruginosa ◽

Parent Strain ◽

Resistance Mechanisms ◽

In Vitro Models ◽

Wild Type ◽

Resistance Development ◽

Development Of Resistance ◽

Pharmacokinetic Profiles ◽

Mutant Prevention Concentration

ABSTRACT In this study we investigated the interplay of antibiotic pharmacokinetic profiles and the development of mutation-mediated resistance in wild-type and hypermutable Pseudomonas aeruginosa strains. We used in vitro models simulating profiles of the commonly used therapeutic drugs meropenem and ceftazidime, two agents with high levels of antipseudomonal activity said to have different potentials for stimulating resistance development. During ceftazidime treatment of the wild-type strain (PAO1), fully resistant mutants overproducing AmpC were selected rapidly and they completely replaced wild-type cells in the population. During treatment with meropenem, mutants of PAO1 were not selected as rapidly and showed only intermediate resistance due to the loss of OprD. These mutants also replaced the parent strain in the population. During the treatment of the mutator P. aeruginosa strain with meropenem, the slowly selected mutants did not accumulate several resistance mechanisms but only lost OprD and did not completely replace the parent strain in the population. Our results indicate that the commonly used dosing regimens for meropenem and ceftazidime cannot avoid the selection of mutants of wild-type and hypermutable P. aeruginosa strains. For the treatment outcome, including the prevention of resistance development, it would be beneficial for the antibiotic concentration to remain above the mutant prevention concentration for a longer period of time than it does in present regimens.

Download Full-text

A Critical Evaluation of Newer β-Lactam Antibiotics for Treatment of Pseudomonas aeruginosa Infections

Annals of Pharmacotherapy ◽

10.1177/1060028020974003 ◽

2020 ◽

pp. 106002802097400

Author(s):

Kathleen C. Blomquist ◽

David E. Nix

Keyword(s):

Pseudomonas Aeruginosa ◽

Clinical Data ◽

Therapeutic Potential ◽

Data Extraction ◽

Relevant Literature ◽

Acquired Resistance ◽

Critical Evaluation ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Study Selection

Objective: This article critically evaluates common Pseudomonas aeruginosa resistance mechanisms and the properties newer β-lactam antimicrobials possess to evade these mechanisms. Data Sources: An extensive PubMed, Google Scholar, and ClinicalTrials.gov search was conducted (January 1995 to July 2020) to identify relevant literature on epidemiology, resistance mechanisms, antipseudomonal agents, newer β-lactam agents, and clinical data available pertaining to P aeruginosa. Study Selection and Data Extraction: Relevant published articles and package inserts were reviewed for inclusion. Data Synthesis: Therapeutic options to treat P aeruginosa infections are limited because of its intrinsic and acquired resistance mechanisms. The goal was to identify advances with newer β-lactams and characterize improvements in therapeutic potential for P aeruginosa infections. Relevance to Patient Care and Clinical Practice: Multidrug-resistant (MDR) P aeruginosa isolates are increasingly encountered from a variety of infections. This review highlights potential activity gains of newer β-lactam antibacterial drugs and the current clinical data to support their use. Pharmacists will be asked to recommend or evaluate the use of these agents and need to be aware of information specific to P aeruginosa, which differs from experience derived from Enterobacterales infections. Conclusions: Newer agents, including ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, and cefiderocol, are useful for the treatment of MDR P aeruginosa infections. These agents offer improved efficacy and less toxicity compared with aminoglycosides and polymyxins and can be used for pathogens that are resistant to first-line antipseudomonal β-lactams. Selection of one agent over another should consider availability, turnaround of susceptibility testing, and product cost. Efficacy data specific for pseudomonal infections are limited, and there are no direct comparisons between the newer agents.

Download Full-text

Molecular mechanisms driving the in vivo development of OXA-10-mediated resistance to ceftolozane/tazobactam and ceftazidime/avibactam during treatment of XDR Pseudomonas aeruginosa infections

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa396 ◽

2020 ◽

Vol 76 (1) ◽

pp. 91-100

Author(s):

Jorge Arca-Suárez ◽

Cristina Lasarte-Monterrubio ◽

Bruno-Kotska Rodiño-Janeiro ◽

Gabriel Cabot ◽

Juan Carlos Vázquez-Ucha ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Molecular Mechanisms ◽

Genomic Analysis ◽

Resistance Mechanisms ◽

Comparative Genomic ◽

Development Of Resistance ◽

Structural Impact ◽

Genetic Context

Abstract Background The development of resistance to ceftolozane/tazobactam and ceftazidime/avibactam during treatment of Pseudomonas aeruginosa infections is concerning. Objectives Characterization of the mechanisms leading to the development of OXA-10-mediated resistance to ceftolozane/tazobactam and ceftazidime/avibactam during treatment of XDR P. aeruginosa infections. Methods Four paired ceftolozane/tazobactam- and ceftazidime/avibactam-susceptible/resistant isolates were evaluated. MICs were determined by broth microdilution. STs, resistance mechanisms and genetic context of β-lactamases were determined by genotypic methods, including WGS. The OXA-10 variants were cloned in PAO1 to assess their impact on resistance. Models for the OXA-10 derivatives were constructed to evaluate the structural impact of the amino acid changes. Results The same XDR ST253 P. aeruginosa clone was detected in all four cases evaluated. All initial isolates showed OprD deficiency, produced an OXA-10 enzyme and were susceptible to ceftazidime, ceftolozane/tazobactam, ceftazidime/avibactam and colistin. During treatment, the isolates developed resistance to all cephalosporins. Comparative genomic analysis revealed that the evolved resistant isolates had acquired mutations in the OXA-10 enzyme: OXA-14 (Gly157Asp), OXA-794 (Trp154Cys), OXA-795 (ΔPhe153-Trp154) and OXA-824 (Asn143Lys). PAO1 transformants producing the evolved OXA-10 derivatives showed enhanced ceftolozane/tazobactam and ceftazidime/avibactam resistance but decreased meropenem MICs in a PAO1 background. Imipenem/relebactam retained activity against all strains. Homology models revealed important changes in regions adjacent to the active site of the OXA-10 enzyme. The blaOXA-10 gene was plasmid borne and acquired due to transposition of Tn6746 in the pHUPM plasmid scaffold. Conclusions Modification of OXA-10 is a mechanism involved in the in vivo acquisition of resistance to cephalosporin/β-lactamase inhibitor combinations in P. aeruginosa.

Download Full-text

1764. The Gut: A Veiled Reservoir for Multidrug-resistant Organisms (MDROs) Below the Tip of the Iceberg

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy209.149 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S63-S63

Author(s):

Teppei Shimasaki ◽

Yoona Rhee ◽

Rachel D Yelin ◽

Michelle Ariston ◽

Stefanie Ollison ◽

...

Keyword(s):

Medical Center ◽

Care Center ◽

Tertiary Care ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Targeted Prevention ◽

Prevention Measures ◽

Carbapenem Resistant ◽

Multidrug Resistant Organisms ◽

Clinical Culture

Abstract Background Clinical culture results are sometimes used to estimate the burden of multidrug-resistant organisms (MDROs) in hospitals. The association between positive clinical culture results and prevalence of MDROs in the gut is incompletely understood. Methods Rectal swab or stool samples were collected daily from adult medical intensive care unit (MICU) patients and cultured for target MDROs using selective media between January 2017 and January 2018 at Rush University Medical Center, a 676-bed tertiary-care center in Chicago. Resistance mechanisms were confirmed by phenotypic methods and/or polymerase chain reaction. Clinical culture results during MICU stay were extracted from the hospital information system. Target MDROs included vancomycin-resistant Enterococci (VRE), carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB). Patients with either a study or clinical culture positive for a target MDRO were analyzed. Results We collected 5,086 study samples from 1,661 unique admissions (1,419 patients) and included here data from 413 unique admissions (397 patients) with completed microbiologic analysis. Median (IQR) patient age was 65 (51–75) years and length of MICU stay was 3 (3–4) days. A total of 156 (37.8%) patients had a target MDRO detected from a study sample at any point; 57 (36.5%) patients had >1 MDRO detected. Overall prevalence of these MDROs was found to be 22.5% VRE, 6.5% CRE, 19.8% ESBL, 4.4% CRPA, and 0.7% CRAB. New MDRO acquisition was observed in 58 (14.6%) patients (figure). Once a target MDRO was detected in a study sample, 82.2% of subsequent study samples were positive for that MDRO. Only 13 (5.8%) patients had a positive clinical culture for any target MDRO during their MICU stay (table). Conclusion Clinical cultures capture only the tip of the resistance iceberg and alone are insufficient to guide MDRO-targeted prevention strategies. Universal infection prevention measures are an alternative that may be preferred in settings where overall prevalence of MDROs is moderate or high and patients may be colonized with >1 MDRO. Disclosures All authors: No reported disclosures.

Download Full-text

Effect of changing urine testing orderables and clinician order sets on inpatient urine culture testing: Analysis from a large academic medical center

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2018.356 ◽

2019 ◽

Vol 40 (3) ◽

pp. 281-286 ◽

Cited By ~ 11

Author(s):

Satish Munigala ◽

Rebecca Rojek ◽

Helen Wood ◽

Melanie L. Yarbrough ◽

Ronald R. Jackups ◽

...

Keyword(s):

Urine Culture ◽

Medical Center ◽

Academic Medical Center ◽

Tertiary Care ◽

Temporal Trends ◽

Interrupted Time Series ◽

Vital Role ◽

Order Sets ◽

Urine Testing ◽

The Impact

AbstractObjective:To evaluate the impact of changes to urine testing orderables in computerized physician order entry (CPOE) system on urine culturing practices.Design:Retrospective before-and-after study.Setting:A 1,250-bed academic tertiary-care referral center.Patients:Hospitalized adults who had ≥1 urine culture performed during their stay.Intervention:The intervention (implemented in April 2017) consisted of notifications to providers, changes to order sets, and inclusion of the new urine culture reflex tests in commonly used order sets. We compared the urine culture rates before the intervention (January 2015 to April 2016) and after the intervention (May 2016 to August 2017), adjusting for temporal trends.Results:During the study period, 18,954 inpatients (median age, 62 years; 68.8% white and 52.3% female) had 24,569 urine cultures ordered. Overall, 6,662 urine cultures (27%) were positive. The urine culturing rate decreased significantly in the postintervention period for any specimen type (38.1 per 1,000 patient days preintervention vs 20.9 per 1,000 patient days postintervention; P < .001), clean catch (30.0 vs 18.7; P < .001) and catheterized urine (7.8 vs 1.9; P < .001). Using an interrupted time series model, urine culture rates decreased for all specimen types (P < .05).Conclusions:Our intervention of changes to order sets and inclusion of the new urine culture reflex tests resulted in a 45% reduction in the urine cultures ordered. CPOE system format plays a vital role in reducing the burden of unnecessary urine cultures and should be implemented in combination with other efforts.

Download Full-text

Problematic clinical isolates of Pseudomonas aeruginosa from the university hospitals in Sofia, Bulgaria: current status of antimicrobial resistance and prevailing resistance mechanisms

Journal of Medical Microbiology ◽

10.1099/jmm.0.46986-0 ◽

2007 ◽

Vol 56 (7) ◽

pp. 956-963 ◽

Cited By ~ 17

Author(s):

Tanya Strateva ◽

Vessela Ouzounova-Raykova ◽

Boyka Markova ◽

Albena Todorova ◽

Yulia Marteva-Proevska ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Agents ◽

Carbapenem Resistance ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Clinical Isolates ◽

Current Status ◽

University Hospitals ◽

Active Efflux ◽

Genes Encoding

A total of 203 clinical isolates of Pseudomonas aeruginosa was collected during 2001–2006 from five university hospitals in Sofia, Bulgaria, to assess the current levels of antimicrobial susceptibility and to evaluate resistance mechanisms to antipseudomonal antimicrobial agents. The antibiotic resistance rates against the following antimicrobials were: carbenicillin 93.1 %, azlocillin 91.6 %, piperacillin 86.2 %, piperacillin/tazobactam 56.8 %, ceftazidime 45.8 %, cefepime 48.9 %, cefpirome 58.2 %, aztreonam 49.8 %, imipenem 42.3 %, meropenem 45.5 %, amikacin 59.1 %, gentamicin 79.7 %, tobramycin 89.6 %, netilmicin 69.6 % and ciprofloxacin 80.3 %. A total of 101 of the studied P. aeruginosa isolates (49.8 %) were multidrug resistant. Structural genes encoding class A and class D β-lactamases showed the following frequencies: bla VEB-1 33.1 %, bla PSE-1 22.5 %, bla PER-1 0 %, bla OXA-groupI 41.3 % and bla OXA-groupII 8.8 %. IMP- and VIM-type carbapenemases were not detected. In conclusion, the studied clinical strains of P. aeruginosa were problematic nosocomial pathogens. VEB-1 extended-spectrum β-lactamases appear to have a significant presence among clinical P. aeruginosa isolates from Sofia. Carbapenem resistance was related to non-enzymic mechanisms such as a deficiency of OprD proteins and active efflux.

Download Full-text