scholarly journals Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa)

Author(s):  
Pranita D Tamma ◽  
Samuel L Aitken ◽  
Robert A Bonomo ◽  
Amy J Mathers ◽  
David van Duin ◽  
...  

Abstract Background Antimicrobial-resistant infections are commonly encountered in US hospitals and result in significant morbidity and mortality. This guidance document provides recommendations for the treatment of infections caused by extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Methods A panel of 6 infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated common questions regarding the treatment of ESBL-E, CRE, and DTR-P. aeruginosa infections. Based on review of the published literature and clinical experience, the panel provide recommendations and associated rationale for each recommendation. Because of significant differences in the molecular epidemiology of resistance and the availability of specific anti-infective agents globally, this document focuses on treatment of antimicrobial-resistant infections in the United States. Results Approaches to empiric treatment selection, duration of therapy, and other management considerations are briefly discussed. The majority of guidance focuses on preferred and alternative treatment recommendations for antimicrobial-resistant infections, assuming that the causative organism has been identified and antibiotic susceptibility testing results are known. Treatment recommendations apply to both adults and children. Conclusions The field of antimicrobial resistance is dynamic and rapidly evolving, and the treatment of antimicrobial-resistant infections will continue to challenge clinicians. This guidance document is current as of 17 September 2020. Updates to this guidance document will occur periodically as new data emerge. Furthermore, the panel will expand recommendations to include other problematic gram-negative pathogens in future versions. The most current version of the guidance including the date of publication can be found at www.idsociety.org/practice-guideline/amr-guidance/.

Author(s):  
Pranita D Tamma ◽  
Samuel L Aitken ◽  
Robert A Bonomo ◽  
Amy J Mathers ◽  
David van Duin ◽  
...  

Abstract Background The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. A previous guidance document focused on infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Here, guidance is provided for treating AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia infections. Methods A panel of six infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of AmpC-E, CRAB, and S. maltophilia infections. Answers are presented as suggestions and corresponding rationales. In contrast to guidance in the previous document, published data on optimal treatment of AmpC-E, CRAB, and S. maltophilia infections are limited. As such, guidance in this document is provided as “suggested approaches” based on clinical experience, expert opinion, and a review of the available literature. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. Results Preferred and alternative treatment suggestions are provided, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, duration of therapy, and other management considerations are also discussed briefly. Suggestions apply for both adult and pediatric populations. Conclusions The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections. This document is current as of September 17, 2021 and will be updated annually. The most current versions of IDSA documents, including dates of publication, are available at www.idsociety.org/practice-guideline/amr-guidance-2.0/.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S88-S88
Author(s):  
Samuel Simon ◽  
Rosanna Li ◽  
Yu Shia Lin ◽  
Suri Mayer ◽  
Edward Chapnick ◽  
...  

Abstract Background Carbapenem-resistant gram-negative organisms are a continuously mounting threat, underscoring the need for effective antimicrobial stewardship interventions to improve the use of carbapenems. We sought to implement several multidisciplinary antimicrobial stewardship interventions beginning in January 2019 in an effort to reduce unnecessary meropenem use and the incidence of carbapenem-resistant gram-negatives. Methods Prospective audit and feedback was utilized daily in combination with weekly stewardship rounds between an Infectious Diseases pharmacist and physician in the Intensive Care Units. A second Infectious Diseases physician attended weekly interdisciplinary rounds on meropenem high-use units. Meropenem Days of Therapy (DOT) per 1,000 patient days and the incidence of meropenem resistant Pseudomonas aeruginosa and Klebsiella pneumoniae were compared by the chi-square test of proportions. Results Between 2018 and 2019 the institution’s meropenem DOT per 1,000 patient days decreased 33%, from 57 to 38 days per 1,000 patient days (difference, 19 days per 1,000 patient days; p< 0.001). In the hospital antibiogram, the meropenem susceptibility of Pseudomonas aeruginosa over the same time period increased from 71% to 77% of isolates (difference, 6%; p = 0.009). A non-significant decrease in the susceptibility of meropenem to Klebsiella pneumoniae was also observed from 92 to 90% (difference, 2%: p = 0.1658). Conclusion These data support the need for antimicrobial stewardship efforts targeting broad-spectrum antimicrobials such as meropenem. In the setting of a sustained decrease in meropenem use over 12 months, we observed a significant improvement in the percent susceptibility rate of Pseudomonas aeruginosa to meropenem for the first time in five years. Disclosures All Authors: No reported disclosures


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S371-S372
Author(s):  
Dee Shortridge ◽  
Leonard R Duncan ◽  
Michael A Pfaller ◽  
Robert K Flamm

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 nosocomial pneumonia. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance to gram-negative (GN) isolates worldwide. In this study, the activities of C-T and comparators vs. GN isolates from each of the 9 US Census divisions were compared. Methods A total of 18,856 Enterobacteriaceae (ENT) and 4,735 Pseudomonas aeruginosa (PSA) isolates were collected from 32 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), ceftazidime (CAZ), colistin (COL), meropenem (MER), and piperacillin-tazobactam (TZP). The following resistant phenotypes were analyzed for ENT: carbapenem resistant (CRE); extended-spectrum β-lactamase phenotype screen-positive (ESBL); and ESBL, nonCRE. or PSA, MER-nonsusceptible (NS), TZP-NS, and CAZ-NS isolates were analyzed. CLSI (2017) interpretive criteria were used. Results For all ENT, 94.2% were S to C-T, 91.5% were S to TZP, 98.0% were S to MER, and 98.8% were S to AMK; 1,697 (9.0%) were ESBL, nonCRE and 356 (1.9%) were CRE. For all PSA isolates, 97.4% were S to C-T, 99.3% were S to COL, 96.9% were S to AMK, and 81.2% were S to MER. The % C-T S for each division (DIV) are shown in the table. The % C-T S for ENT ranged from 98.1% (DIV 4) to 87.4% (DIV 2) and % C-T S for ESBL, nonCRE ranged from 93.8% in DIV 4 to 79.8% in DIV 7. For PSA, the % C-T S ranged from 99.6% in DIV 4 to 94.9% in DIV 9. Activity of C-T against PSA NS to MER, CAZ or TZP varied by division and was >80% for all except DIV 9. Conclusion Against PSA, only COL was more active than C-T. C-T demonstrated potent activity against PSA NS to other β-lactams. For ENT, overall activity was good. For both PSA and ENT, C-T varied by DIV. 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


2019 ◽  
Vol 6 (7) ◽  
Author(s):  
Ayesha Khan ◽  
Truc T Tran ◽  
Rafael Rios ◽  
Blake Hanson ◽  
William C Shropshire ◽  
...  

Abstract Background Treatment of serious infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa remains a challenge, despite the introduction of novel therapeutics. In this study, we report 2 extensively drug-resistant clinical isolates of sequence type (ST) 309 P aeruginosa resistant to all β-lactams, including the novel combinations ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam. Methods Isolates were sequenced using both short-read (Illumina) and long-read technology to identify resistance determinants, polymorphisms (compared with P aeruginosa PAO1), and reconstruct a phylogenetic tree. A pair of β-lactamases, Guiana extended spectrum β-lactamase (GES)-19 and GES-26, were cloned and expressed in a laboratory strain of Escherichia coli to examine their relative impact on resistance. Using cell lysates from E coli expressing the GES genes individually and in tandem, we determined relative rates of hydrolysis for nitrocefin and ceftazidime. Results Two ST309 P aeruginosa clinical isolates were found to harbor the extended spectrum β-lactamases GES-19 and GES-26 clustered in tandem on a chromosomal class 1 integron. The presence of both enzymes in E coli was associated with significantly elevated minimum inhibitory concentrations to aztreonam, cefepime, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam, compared with those expressed individually. The combination of ceftazidime/avibactam plus aztreonam was active in vitro and used to achieve cure in one patient. Phylogenetic analysis revealed ST309 P aeruginosa are closely related to MDR strains from Mexico also carrying tandem GES. Conclusions The presence of tandem GES-19 and GES-26 is associated with resistance to all β-lactams, including ceftolozane/tazobactam. Phylogenetic analysis suggests that ST309 P aeruginosa may be an emerging threat in the United States.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S237-S237
Author(s):  
Allison C Brown ◽  
Sarah Malik ◽  
Jennifer Huang ◽  
Amelia Bhatnagar ◽  
Rocio Balbuena ◽  
...  

Abstract Background Infections with metallo-β-lactamase (MBL)-producing organisms are emerging in the United States. Treatment options for these infections are limited. We describe MBL genes among carbapenemase positive carbapenem-resistant Enterobacteriaceae (CP-CRE) and Pseudomonas aeruginosa (CP-CRPA) isolates tested during the first two years of the Antibiotic Resistance Laboratory Network (AR Lab Network). Methods State and local public health laboratories tested CRE and CRPA isolates for organism identification, antimicrobial susceptibility, and PCR-based detection of blaKPC, blaNDM, blaOXA-48-like, blaVIM, and blaIMP carbapenemase genes. All testing results were sent to CDC at least monthly. Results Since January 2017, the AR Lab Network tested 21,733 CRE and 14,141 CRPA. CP-CRE were detected in 37% of CRE; 2% of CRPA were CP-CRPA. Among CP-CRE, 9% (686/8016) were MBL-producers (NDM, VIM, or IMP). Among MBL-producers, a blaNDM gene was detected most often (81%; 551/686). blaNDM were most common among Klebsiella spp. (47%; 261/551), blaIMP were most common among Providencia spp. (53%; 40/75), blaVIM was most common among Enterobacter spp. (19%; 25/62). Twelve percent (96) of MBL CP-CRE contained more than one carbapenemase gene. Among CP-CRPA, 73% (218/300) were MBL producers and blaVIM was the most common gene (62%; 186). Three (1%) MBL CP-CRPA contained more than one carbapenemase. Conclusion Increased testing of CRE and CRPA isolates through the AR Lab Network has facilitated early and rapid detection of hard-to-treat infections caused by MBL-producing organisms across the United States. The widespread distribution of MBL genes highlights the continued need for containment strategies that help prevent transmission between patients and among healthcare facilities. To support therapeutic decisions for severe infections caused by MBL-producing organisms, the AR Lab Network is now offering rapid susceptibility testing against aztreonam/avibactam, using digital dispenser technology. This testing program aims to close the gap between the availability of new drugs or drug combinations and the availability of commercial AST methods, thereby improving patient safety and antimicrobial stewardship. Disclosures All authors: No reported disclosures.


2011 ◽  
Vol 55 (6) ◽  
pp. 2710-2713 ◽  
Author(s):  
Guo-Bao Tian ◽  
Jennifer M. Adams-Haduch ◽  
Tatiana Bogdanovich ◽  
Hong-Ning Wang ◽  
Yohei Doi

ABSTRACTA novel extended-spectrum β-lactamase (ESBL) was identified in aPseudomonas aeruginosaclinical isolate obtained from a patient admitted to a hospital in Pennsylvania in 2008. The patient had a prolonged hospitalization in a hospital in Dubai, United Arab Emirates, before being transferred to the United States. The novel ESBL, designated PME-1 (Pseudomonas aeruginosaESBL 1), is a molecular class A, Bush-Jacoby-Medeiros group 2be enzyme and shared 50, 43, and 41% amino acid identity with the L2 β-lactamase ofStenotrophomonas maltophilia, CTX-M-9, and KPC-2, respectively. PME-1 conferred clinically relevant resistance to ceftazidime, cefotaxime, cefepime, and aztreonam inP. aeruginosaPAO1 but not to carbapenems. Purified PME-1 showed good hydrolytic activity against ceftazidime, cefotaxime, and aztreonam, while activity against carbapenems and cefepime could not be measured. PME-1 was inhibited well by β-lactamase inhibitors, including clavulanic acid, sulbactam, and tazobactam. TheblaPME-1gene was carried by an approximately 9-kb plasmid and flanked by tandem ISCR24elements.


2018 ◽  
Vol 66 (7) ◽  
pp. 987-994 ◽  
Author(s):  
L Clifford McDonald ◽  
Dale N Gerding ◽  
Stuart Johnson ◽  
Johan S Bakken ◽  
Karen C Carroll ◽  
...  

Abstract A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.


Burns ◽  
2014 ◽  
Vol 40 (8) ◽  
pp. 1556-1561 ◽  
Author(s):  
Davood Kalantar Neyestanaki ◽  
Akbar Mirsalehian ◽  
Fereshteh Rezagholizadeh ◽  
Fereshteh Jabalameli ◽  
Morovat Taherikalani ◽  
...  

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S243-S243
Author(s):  
Sukhjit Takhar ◽  
Anusha Krishnadasan ◽  
Gregory J Moran ◽  
William Mower ◽  
Kavitha Pathmarajah ◽  
...  

Abstract Background Gram-negative infections due to extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, and carbapenem-resistant Enterobacteriaceae (CRE) and non-fermenting (CR-NF) strains, are increasingly encountered. Study objectives were to determine prevalence and associated risk factors and outcomes for these strains among emergency department patients hospitalized for urinary tract infection (UTI) at 11 US hospitals. Methods This was a prospective observational study of patients ≥18 years hospitalized for UTI. Clinical data were collected at the index visit. Urine was obtained for culture and susceptibility testing. Electronic medical record and telephone follow-up were conducted after 30 days for site laboratory results, treatment, and clinical outcomes. Positive culture was defined as 1 uropathogen with growth at ≥104 cfu/mL, or 2 with 1 or both at ≥105 cfu/mL, or ≥3 with 1 or 2 at ≥105 cfu/mL. Isolates with ceftriaxone (CRO) or meropenem MIC >1 μg/mL will undergo reference laboratory (IHMA, Inc., Schaumburg, IL) susceptibility testing, including against newer antibiotics and cefiderocol. Results We enrolled 774 participants between 2018 and 2019; 289 (37.3%) excluded due to urine culture not done, no growth, or contamination. Of 485 culture-positive participants (median age 56 years, 62.0% female), 432 (89.1%) grew 1 uropathogen, 48 (9.9%) 2, and 5 (1.0%) ≥3. Prevalences of CRO-resistant Enterobacteriaceae, CRE, and CR-NF were 19.9%, 2.1%, and 10.7%, respectively. At sites, 95.7% of CRO-resistant Enterobacteriaceae isolates were ESBL. Among participants with any or no antibiotic resistance risk factors, i.e., antibiotics, hospitalization, long-term care, or travel within 90 days, prevalence of CRO-resistant Enterobacteriaceae was 68/228 (29.8%) and 10/155 (6.5%), respectively. Among those with CRO-resistant vs. susceptible Enterobacteriaceae infections, ICU admission and death occurred in 9.9% vs. 6.6% and 3.7% vs. 1.0%, with median time home over 30 days, 24 vs. 27 days, respectively. Conclusion Among US hospitalized patients with UTI, infections due to CRE remain uncommon; however, ESBL and CR-NF now account for a substantial proportion of cases and are associated with resistance risk factors and worse outcomes. Disclosures All authors: No reported disclosures.


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