A Combination Antibiogram Evaluation for Pseudomonas aeruginosa in Respiratory and Blood Sources from Intensive Care Unit (ICU) and Non-ICU Settings in U.S. Hospitals

ABSTRACT Pseudomonas aeruginosa is an important pathogen associated with significant morbidity and mortality. U.S. guidelines for the treatment of hospital-acquired and ventilator-associated pneumonia recommend the use of two antipseudomonal drugs for high-risk patients to ensure that ≥95% of patients receive active empirical therapy. We evaluated the utility of combination antibiograms in identifying optimal anti-P. aeruginosa drug regimens. We conducted a retrospective cross-sectional analysis of the antimicrobial susceptibility of all nonduplicate P. aeruginosa blood and respiratory isolates collected between 1 October 2016 and 30 September 2017 from 304 U.S. hospitals in the BD Insights Research Database. Combination antibiograms were used to determine in vitro rates of susceptibility to potential anti-P. aeruginosa combination regimens consisting of a backbone antibiotic (an extended-spectrum cephalosporin, carbapenem, or piperacillin-tazobactam) plus an aminoglycoside or fluoroquinolone. Single-agent susceptibility rates for the 11,701 nonduplicate P. aeruginosa isolates ranged from 72.7% for fluoroquinolones to 85.0% for piperacillin-tazobactam. Susceptibility rates were higher for blood isolates than for respiratory isolates (P < 0.05). Antibiotic combinations resulted in increased susceptibility rates but did not achieve the goal of 95% antibiotic coverage. Adding an aminoglycoside resulted in higher susceptibility rates than adding a fluoroquinolone; piperacillin-tazobactam plus an aminoglycoside resulted in the highest susceptibility rate (93.3%). Intensive care unit (ICU) isolates generally had lower susceptibility rates than non-ICU isolates. Commonly used antipseudomonal drugs, either alone or in combination, did not achieve 95% coverage against U.S. hospital P. aeruginosa isolates, suggesting that new drugs are needed to attain this goal. Local institutional use of combination antibiograms has the potential to optimize empirical therapy of infections caused by difficult-to-treat pathogens.

Download Full-text

Antimicrobial Resistance Profile of MDR & Non-MDR Meropenem-Resistant Pseudomonas aeruginosa Isolates of Patients in Intensive Care Unit of Tertiary Hospital

Indonesian Journal of Tropical and Infectious Disease ◽

10.20473/ijtid.v9i3.30000 ◽

2021 ◽

Vol 9 (3) ◽

pp. 152

Author(s):

Imaculata Sonia Vidaryo Lameng ◽

Ni Nyoman Sri Budayanti ◽

Luh Inta Prilandari ◽

I Ketut Agus Indra Adhiputra

Keyword(s):

Intensive Care Unit ◽

Pseudomonas Aeruginosa ◽

Intensive Care ◽

Antimicrobial Resistance ◽

Empirical Therapy ◽

Tertiary Hospital ◽

Clinical Microbiology Laboratory ◽

Cross Sectional ◽

Resistance Profile ◽

Control Programs

Pseudomonas aeruginosa is one of the gram-negative bacteria that causes infection in the Intensive Care Unit (ICU) which is easily resistant. Patients infected with carbapenem-resistant P. aeruginosa are predicted to have a poor prognosis. This study aims to know the resistance profile of meropenem-resistant P. aeruginosa in the ICU. The results of this study can be used as a measure on the success of antimicrobial resistance control, infection control programs and become a reference for empirical therapy in the ICU. This study used a cross-sectional retrospective descriptive research method and was carried out at the Clinical Microbiology Laboratory of Sanglah Hospital Denpasar for three years, from 2018 to 2020. The results showed 38 of the 93 isolates of P. aeruginosa in the ICU were resistant to meropenem and were derived from sputum and urine. The percentage of meropenem-resistant P. aeruginosa isolates was higher in the multi-drug-resistant group and mostly came from sputum specimens. In 2018, Non-MDR meropenem-resistant P. aeruginosa isolates was that 100% sensitive to all other antibiotics used to treat P. aeruginosa infections, including; ceftazidime, cefepime, ciprofloxacin, gentamicin, amikacin, and piperacillin-tazobactam. In 2019 no meropenem-resistant P. aeruginosa isolates were found. In 2020, its sensitivity to antibiotics ceftazidime and piperacillin-tazobactam was 20.0%, ciprofloxacin 60.0% and to antibiotics gentamicin and amikacin 100%. MDR meropenem-resistant P. aeruginosa isolates in 2018 were still sensitive to ceftazidime (15.4%) and amikacin (69.2%) antibiotics, while in 2019 they were only sensitive to amikacin (37.5%). In 2020, P. aeruginosa isolates were sensitive to the antibiotics ceftazidime and cefepime (11.1%), piperacillin-tazobactam (22.2%), and amikacin (88.9%). Amikacin may be the choice of treatment for MDR meropenem-resistant P. aeruginosa.

Download Full-text

Serratia marcescans Contamination of Antiseptic Soap Containing Triclosan: Implications for Nosocomial Infection

Infection Control ◽

10.1017/s0195941700060690 ◽

1984 ◽

Vol 5 (9) ◽

pp. 427-430 ◽

Cited By ~ 29

Author(s):

M. Anita Barry ◽

Donald E. Craven ◽

Theresa A. Goularte ◽

Deborah A. Lichtenberg

Keyword(s):

Intensive Care Unit ◽

Pseudomonas Aeruginosa ◽

Intensive Care ◽

Nosocomial Infection ◽

Surgical Intensive Care Unit ◽

Minimal Bactericidal Concentration ◽

Surgical Intensive Care ◽

Time Kill ◽

The Impact

Abstract During a recent investigation in our surgical intensive care unit, we found that several bottles of the antiseptic handwashing soap, OR Scrub®, were contaminated with Serratia marcescens. OR Scrub® contains 1% triclosan, lanolin, and detergents. The antimicrobial efficacy of OR Scrub® was examined in vitro using serial two-fold dilutions of soap inoculated with various concentrations of different nosocomial pathogens. The minimal bactericidal concentration (MBC) of OR Scrub® against Pseudomonas aeruginosa and several strains of S. marcescens was ≤1:2 By comparison, a non-antiseptic soap from the same manufacturer (Wash®) and 4% chlorhexidine (Hibiclens®) had MBCs for all strains tested of at least 1:64. Time-kill curves confirmed the findings of the initial experiments.This is the first report of extrinsic contamination of antiseptic soap containing triclosan. No infections could be attributed to the contaminated soap, but sporadic outbreaks of Serratia have occurred in the intensive care unit with no identifiable source. Although there have been few studies on the impact of antiseptic soap in reducing nosocomial infection, we question whether a soap with the limitations of OR Scrub® should be used in intensive care units or operating rooms.

Download Full-text

Carbapenem-Nonsusceptible Pseudomonas aeruginosa Isolates from Intensive Care Units in the United States: a Potential Role for New β-Lactam Combination Agents

Journal of Clinical Microbiology ◽

10.1128/jcm.00535-19 ◽

2019 ◽

Vol 57 (8) ◽

Cited By ~ 14

Author(s):

Tomefa E. Asempa ◽

David P. Nicolau ◽

Joseph L. Kuti

Keyword(s):

Pseudomonas Aeruginosa ◽

Intensive Care ◽

Respiratory Tract ◽

Potential Role ◽

The United States ◽

Content Type ◽

New Antibiotics ◽

Susceptibility Profiles ◽

Lactamase Inhibitor

ABSTRACT Pseudomonas aeruginosa, a frequent pathogen in the intensive care unit (ICU), has the propensity to develop antibiotic resistance. In particular, carbapenem-nonsusceptible (NS) P. aeruginosa poses tremendous challenges, and new antibiotics will be needed to treat this phenotype. Here we determine carbapenem nonsusceptibility rates for contemporary P. aeruginosa isolates from U.S. ICUs and in vitro activities of new β-lactam combination agents. Between July 2017 and June 2018, consecutive nonduplicate P. aeruginosa isolates from blood and respiratory tract sources were recovered from patients admitted to the ICUs of 36 geographically diverse U.S. hospitals. Antimicrobial susceptibility to the following antipseudomonal agents was tested: ceftazidime, imipenem, meropenem, ceftazidime-avibactam, and imipenem-relebactam (an investigational β-lactam/β-lactamase inhibitor). MICs and susceptibility rates were measured using Clinical and Laboratory Standards Institute reference broth microdilution methodology. Among the 538 consecutive ICU P. aeruginosa isolates collected, carbapenem nonsusceptibility was observed for 35% of the isolates and was more common among respiratory tract versus bloodstream specimens. Susceptibility rates, MIC50 values, and MIC90 values were as follows: ceftazidime-avibactam, 92.8%, 2 μg/ml, and 8 μg/ml; imipenem-relebactam, 91.5%, 0.25 μg/ml, and 2 μg/ml; ceftazidime, 77.1%, 4 μg/ml, and 64 μg/ml; meropenem, 72.7%, 1 μg/ml, and 16 μg/ml; imipenem, 67.1%, 2 μg/ml, and 16 μg/ml. Most (>75%) of the carbapenem-NS isolates were susceptible to ceftazidime-avibactam and imipenem-relebactam. In these U.S. hospital ICUs, carbapenem-NS P. aeruginosa isolates from respiratory sources were frequently observed. Novel β-lactam combination agents appear to retain active in vitro susceptibility profiles against these isolates and may play a role in the treatment of infections caused by carbapenem-NS P. aeruginosa strains.

Download Full-text

In Vitro Comparison of Ceftolozane-Tazobactam to Traditional Beta-Lactams and Ceftolozane-Tazobactam as an Alternative to Combination Antimicrobial Therapy for Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01350-17 ◽

2017 ◽

Vol 61 (12) ◽

Cited By ~ 16

Author(s):

Kellie J. Goodlet ◽

David P. Nicolau ◽

Michael D. Nailor

Keyword(s):

Pseudomonas Aeruginosa ◽

Single Agent ◽

Cross Resistance ◽

Combination Therapies ◽

Beta Lactams ◽

Content Type ◽

Risk Patients ◽

Hospital Acquired Pneumonia ◽

Hospital Acquired

ABSTRACT Guidelines for the treatment of sepsis, febrile neutropenia, and hospital-acquired pneumonia caused by Pseudomonas aeruginosa include empirical regimens incorporating two antibiotics from different classes with activity against P. aeruginosa for select at-risk patients to increase the likelihood that the organism will be susceptible to at least one agent. The activity against P. aeruginosa and the rates of cross-resistance of ceftolozane-tazobactam were compared to those of the β-lactam comparators cefepime, ceftazidime, piperacillin-tazobactam, and meropenem alone and cumulatively with ciprofloxacin or tobramycin. Nonurine P. aeruginosa isolates were collected from adult inpatients at 44 geographically diverse U.S. hospitals. MICs were determined using reference broth microdilution methods. Of the 1,257 isolates collected, 29% were from patients in intensive care units and 39% were from respiratory sites. The overall rate of susceptibility to ceftolozane-tazobactam was high at 97%, whereas it was 72 to 76% for cefepime, ceftazidime, piperacillin-tazobactam, and meropenem. The rate of nonsusceptibility to all four comparator β-lactams was 11%; of the isolates nonsusceptible to the four comparator β-lactams, 80% remained susceptible to ceftolozane-tazobactam. Among the isolates nonsusceptible to the tested β-lactam comparators, less than half were susceptible to ciprofloxacin. By comparison, approximately 80% of the β-lactam-nonsusceptible isolates were susceptible to tobramycin, for overall cumulative susceptibility rates of 94 to 95%, nearly 10% higher than that of the ciprofloxacin–β-lactam combinations and approaching that of ceftolozane-tazobactam as a single agent. The rates of susceptibility to ceftolozane-tazobactam were consistently high, with little observable cross-resistance. Ceftolozane-tazobactam monotherapy performed at or above the level of commonly utilized combination therapies on the basis of in vitro susceptibilities. Ceftolozane-tazobactam should be considered for use in patients at high risk for resistant P. aeruginosa infection and as an alternative to empirical combination therapy, especially for patients unable to tolerate aminoglycosides.

Download Full-text

Comparison of Septic Shock Due to Multidrug-ResistantAcinetobacter baumanniiorKlebsiella pneumoniaeCarbapenemase-ProducingK. pneumoniaein Intensive Care Unit Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02562-17 ◽

2018 ◽

Vol 62 (6) ◽

Cited By ~ 10

Author(s):

Alessandro Russo ◽

Simone Giuliano ◽

Giancarlo Ceccarelli ◽

Francesco Alessandri ◽

Alessandra Giordano ◽

...

Keyword(s):

Intensive Care Unit ◽

Septic Shock ◽

Intensive Care ◽

Clinical Features ◽

Mortality Rates ◽

Multidrug Resistant ◽

Simplified Acute Physiology Score ◽

Content Type ◽

Definitive Therapy

ABSTRACTA significant cause of mortality in the intensive care unit (ICU) is multidrug-resistant (MDR) Gram-negative bacteria, such as MDRAcinetobacter baumannii(MDR-AB) andKlebsiella pneumoniaecarbapenemase-producingK. pneumoniae(KPC-Kp). The aim of the present study was to compare the clinical features, therapy, and outcome of patients who developed septic shock due to either MDR-AB or KPC-Kp. We retrospectively analyzed patients admitted to the ICU of a teaching hospital from November 2010 to December 2015 who developed septic shock due to MDR-AB or KPC-Kp infection. Data from 220 patients were analyzed: 128 patients (58.2%) were diagnosed with septic shock due to KPC-Kp, and 92 patients (41.8%) were diagnosed with septic shock due to MDR-AB. The 30-day mortality rate was significantly higher for the MDR-AB group than the KPC-Kp group (84.8% versus 44.5%, respectively;P< 0.001). Steroid exposure and pneumonia were associated with MDR-AB infection, whereas hospitalization in the previous 90 days, primary bacteremia, and KPC-Kp colonization were associated with KPC-Kp infection. For patients with KPC-Kp infections, the use of ≥2in vitro-active antibiotics as empirical or definitive therapy was associated with higher 30-day survival, while isolation of colistin-resistant strains was linked to mortality. Patients with MDR-AB infections, age >60 years, and a simplified acute physiology score II (SAPS II) of >45 points were associated with increased mortality rates. We concluded that septic shock due to MDR-AB infection is associated with very high mortality rates compared to those with septic shock due to KPC-Kp. Analysis of the clinical features of these critically ill patients might help physicians in choosing appropriate empirical antimicrobial therapy.

Download Full-text

Potent LpxC Inhibitors with In Vitro Activity against Multidrug-Resistant Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00977-19 ◽

2019 ◽

Vol 63 (11) ◽

Cited By ~ 7

Author(s):

Kevin M. Krause ◽

Cat M. Haglund ◽

Christy Hebner ◽

Alisa W. Serio ◽

Grace Lee ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Lipid A ◽

Phase 1 ◽

Multidrug Resistant ◽

New Drugs ◽

Therapeutic Window ◽

Content Type ◽

Lipid A Biosynthesis ◽

Essential Enzyme

ABSTRACT New drugs with novel mechanisms of resistance are desperately needed to address both community and nosocomial infections due to Gram-negative bacteria. One such potential target is LpxC, an essential enzyme that catalyzes the first committed step of lipid A biosynthesis. Achaogen conducted an extensive research campaign to discover novel LpxC inhibitors with activity against Pseudomonas aeruginosa. We report here the in vitro antibacterial activity and pharmacodynamics of ACHN-975, the only molecule from these efforts and the first ever LpxC inhibitor to be evaluated in phase 1 clinical trials. In addition, we describe the profiles of three additional LpxC inhibitors that were identified as potential lead molecules. These efforts did not produce an additional development candidate with a sufficiently large therapeutic window and the program was subsequently terminated.

Download Full-text

Draft Genome Sequences of Four Multidrug-Resistant Pseudomonas aeruginosa Isolates from Hospital Wastewater in Singapore

Microbiology Resource Announcements ◽

10.1128/mra.01193-18 ◽

2018 ◽

Vol 7 (19) ◽

Cited By ~ 1

Author(s):

Charmaine Ng ◽

Xiaoqiong Gu ◽

Shin Giek Goh ◽

Hongjie Chen ◽

Laurence Haller ◽

...

Keyword(s):

Intensive Care Unit ◽

Pseudomonas Aeruginosa ◽

Intensive Care ◽

Draft Genome ◽

Multidrug Resistant ◽

Hospital Wastewater ◽

Beta Lactam ◽

Genome Sequences ◽

Content Type ◽

Beta Lactam Antibiotics

Four multidrug-resistant Pseudomonas aeruginosa isolates were cultured from intensive care unit wastewater. All isolates exhibited resistance to carbapenem and extended-spectrum beta-lactam antibiotics.

Download Full-text

Activity of a New Cephalosporin, CXA-101 (FR264205), against β-Lactam-Resistant Pseudomonas aeruginosa Mutants Selected In Vitro and after Antipseudomonal Treatment of Intensive Care Unit Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01104-09 ◽

2010 ◽

Vol 54 (3) ◽

pp. 1213-1217 ◽

Cited By ~ 66

Author(s):

Bartolome Moya ◽

Laura Zamorano ◽

Carlos Juan ◽

José L. Pérez ◽

Yigong Ge ◽

...

Keyword(s):

Intensive Care Unit ◽

Pseudomonas Aeruginosa ◽

Intensive Care ◽

Efflux Pump ◽

Multidrug Resistant ◽

Icu Patients ◽

Resistant Strains ◽

High Level ◽

Level Resistance

ABSTRACT CXA-101, previously designated FR264205, is a new antipseudomonal cephalosporin. We evaluated the activity of CXA-101 against a highly challenging collection of β-lactam-resistant Pseudomonas aeruginosa mutants selected in vitro and after antipseudomonal treatment of intensive care unit (ICU) patients. The in vitro mutants investigated included strains with multiple combinations of mutations leading to several degrees of AmpC overexpression (ampD, ampDh2, ampDh3, and dacB [PBP4]) and porin loss (oprD). CXA-101 remained active against even the AmpD-PBP4 double mutant (MIC = 2 μg/ml), which shows extremely high levels of AmpC expression. Indeed, this mutant showed high-level resistance to all tested β-lactams, except carbapenems, including piperacillin-tazobactam (PTZ), aztreonam (ATM), ceftazidime (CAZ), and cefepime (FEP), a cephalosporin considered to be relatively stable against hydrolysis by AmpC. Moreover, CXA-101 was the only β-lactam tested (including the carbapenems imipenem [IMP] and meropenem [MER]) that remained fully active against the OprD-AmpD and OprD-PBP4 double mutants (MIC = 0.5 μg/ml). Additionally, we tested a collection of 50 sequential isolates that were susceptible or resistant to penicillicins, cephalosporins, carbapenems, or fluoroquinolones that emerged during treatment of ICU patients. All of the mutants resistant to CAZ, FEP, PTZ, IMP, MER, or ciprofloxacin showed relatively low CXA-101 MICs (range, 0.12 to 4 μg/ml; mean, 1 to 2 μg/ml). CXA-101 MICs of pan-β-lactam-resistant strains ranged from 1 to 4 μg/ml (mean, 2.5 μg/ml). As described for the in vitro mutants, CXA-101 retained activity against the natural AmpD-PBP4 double mutants, even when these exhibited additional overexpression of the MexAB-OprM efflux pump. Therefore, clinical trials are needed to evaluate the usefulness of CXA-101 for the treatment of P. aeruginosa nosocomial infections, particularly those caused by multidrug-resistant isolates that emerge during antipseudomonal treatments.

Download Full-text