ARGONAUT-III and -V: susceptibility of carbapenem-resistant Klebsiella pneumoniae and multidrug-resistant Pseudomonas aeruginosa to the bicyclic boronate ß-lactamase inhibitor taniborbactam combined with cefepime.

Taniborbactam, a bicyclic boronate ß-lactamase inhibitor with activity against Klebsiella pneumoniae carbapenemase (KPC), Verona integron-encoded metallo-ß-lactamase (VIM), New Delhi metallo-ß-lactamase (NDM), extended-spectrum beta-lactamases (ESBLs), OXA-48, and AmpC ß-lactamases, is under clinical development in combination with cefepime. Susceptibility of 200 previously characterized carbapenem-resistant K. pneumoniae and 197 multidrug-resistant (MDR) Pseudomonas aeruginosa to cefepime-taniborbactam and comparators was determined by broth microdilution. For K. pneumoniae (192 KPC; 7 OXA-48-related), MIC90 values of ß-lactam components for cefepime-taniborbactam, ceftazidime-avibactam, and meropenem-vaborbactam were 2, 2, and 1 mg/L, respectively. For cefepime-taniborbactam, 100% and 99.5% of isolates of K. pneumoniae were inhibited at ≤16 mg/L and ≤8 mg/L, respectively, while 98.0% and 95.5% of isolates were susceptible to ceftazidime-avibactam and meropenem-vaborbactam, respectively. For P. aeruginosa, MIC90 values of ß-lactam components of cefepime-taniborbactam, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam were 16, >8, >8, and >4 mg/L, respectively. Of 89 carbapenem-susceptible isolates, 100% were susceptible to ceftolozane-tazobactam, ceftazidime-avibactam, and cefepime-taniborbactam at ≤8 mg/L. Of 73 carbapenem-intermediate/resistant P. aeruginosa isolates without carbapenemases, 87.7% were susceptible to ceftolozane-tazobactam, 79.5% to ceftazidime-avibactam, and 95.9% and 83.6% to cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively. Cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively, was active against 73.3% and 46.7% of 15 VIM- and 60.0% and 35.0% of 20 KPC-producing P. aeruginosa isolates. Of all 108 carbapenem-intermediate/resistant P. aeruginosa isolates, cefepime-taniborbactam was active against 86.1% and 69.4% at ≤16 mg/L and ≤8 mg/L, respectively, compared to 59.3% for ceftolozane-tazobactam and 63.0% for ceftazidime-avibactam. Cefepime-taniborbactam had in vitro activity comparable to ceftazidime-avibactam and greater than meropenem-vaborbactam against carbapenem-resistant K. pneumoniae and carbapenem-intermediate/resistant MDR P. aeruginosa.

Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections.

BACKGROUND: The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant (AMR) infections. This guidance document focuses on infections caused by extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E), AmpC ß- lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa with difficult-to-treat resistance (DTR P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. This updated document replaces previous versions of the guidance document. METHODS: A panel of six infectious diseases specialists with expertise in managing antimicrobial- resistant infections formulated questions about the treatment of infections caused by ESBL-E, AmpC-E, CRE, DTR P. aeruginosa, CRAB, and S. maltophilia. Because of differences in the epidemiology of AMR and availability of specific anti-infectives internationally, this document focuses on the treatment of AMR infections in the United States. RESULTS: Preferred and alternative suggested treatment approaches are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, transitioning to oral therapy, duration of therapy, and other management considerations are discussed briefly. Suggested approaches apply for both adult and pediatric populations, although suggested antibiotic dosages are provided only for adults. CONCLUSIONS: The field of AMR is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of AMR infections. This document is current as of December 31, 2023 and will be updated periodically. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance/.

Impact of Veterans Affairs Geriatric Research, Education, and Clinical Centers: Incubators of innovation in geriatrics.

Since their inception in 1975, the Department of Veterans Affairs Geriatric Research, Education, and Clinical Centers (GRECCs) have served as incubators of innovation in geriatrics. Their contributions to the VA mission were last reviewed in 2012. Herein, we describe the continuing impact of GRECCs in research, clinical, and educational areas, focusing on the period between 2018 and 2022. GRECC research spans the continuum from bench to bedside, with a growing research portfolio notable for highly influential publications. GRECC education connects healthcare professions trainees and practicing clinicians, as well as Veterans and their caregivers, to engaging learning experiences. Clinical advancements, including age-friendly care, span the continuum of care and leverage technology to link disparate geographical sites. GRECCs are uniquely positioned to serve older adults given their alignment with the largest integrated health system in the United States and their integration with academic health centers. As such, the GRECCs honor Veterans as they age by building VA capacity to care for the increasing number of aging Veterans seeking care from VA. GRECC advancements also benefit non-VA healthcare systems, their academic affiliates, and non-Veteran older adults. GRECCs make invaluable contributions to advancing geriatric and gerontological science, training healthcare professionals, and developing innovative models of geriatric care.

The interaction of the azetidine thiazole side chain with the active site loop (ASL) 3 drives the evolution of IMP metallo-ß-lactamase against tebipenem.

Imipenemase (IMP) metallo-ß-lactamases (MBLs) hydrolyze almost all available ß-lactams including carbapenems and are not inhibited by any commercially available ß-lactamase inhibitor. Tebipenem (TP) pivoxil is the first orally available carbapenem and possesses a unique bicyclic azetidine thiazole moiety located at the R2 position. TP has potent in vitro activity against Enterobacterales producing extended-spectrum and/or AmpC ß-lactamases. Thus far, the activity of TP against IMP-producing strains is understudied. To address this knowledge gap, we explored the structure activity relationships of IMP MBLs by investigating whether IMP-6, IMP-10, IMP-25, and IMP-78 [MBLs with expanded hydrolytic activity against meropenem (MEM)] would demonstrate enhanced activity against TP. Most of the Escherichia coli DH10B strains expressing IMP-1 variants displayed a ≥twofold MIC difference between TP and MEM, while those expressing VIM or NDM variants demonstrated comparable MICs. Catalytic efficiency (kcat/KM) values for the TP hydrolysis by IMP-1, IMP-6, IMP-10, IMP-25, and IMP-78 were significantly lower than those obtained for MEM. Molecular dynamic simulations reveal that V67F and S262G substitutions (found in IMP-78) reposition active site loop 3, ASL-3, to better accommodate the bicyclic azetidine thiazole side chain, allowing microbiological/catalytic activity to approach that of comparison MBLs used in this study. These findings suggest that modifying the R2 side chain of carbapenems can significantly impact hydrolytic stability. Furthermore, changes in conformational dynamics due to single amino acid substitutions should be used to inform drug design of novel carbapenems.

Crystal structure of the class A extended-spectrum ß-lactamase CTX-M-96 in complex with relebactam at 1.03 Angstrom resolution.

The use of ß-lactam/ß-lactamase inhibitors constitutes an important strategy to counteract ß-lactamases in multidrug-resistant (MDR) Gram-negative bacteria. Recent reports have described ceftazidime-/avibactam-resistant isolates producing CTX-M variants with different amino acid substitutions (e.g., P167S, L169Q, and S130G). Relebactam (REL) combined with imipenem has proved very effective against Enterobacterales producing ESBLs, serine-carbapenemases, and AmpCs. Herein, we evaluated the inhibitory efficacy of REL against CTX-M-96, a CTX-M-15-type variant. The CTX-M-96 structure was obtained in complex with REL at 1.03 Å resolution (PDB 8EHH). REL was covalently bound to the S70-Oγ atom upon cleavage of the C7-N6 bond. Compared with apo CTX-M-96, binding of REL forces a slight displacement of the deacylating water inwards the active site (0.81 Å), making the E166 and N170 side chains shift to create a proper hydrogen bonding network. Binding of REL also disturbs the hydrophobic patch formed by Y105, P107, and Y129, likely due to the piperidine ring of REL that creates clashes with these residues. Also, a remarkable change in the positioning of the N104 sidechain is also affected by the piperidine ring. Therefore, differences in the kinetic behavior of REL against class A ß-lactamases seem to rely, at least in part, on differences in the residues being involved in the association and stabilization of the inhibitor before hydrolysis. Our data provide the biochemical and structural basis for REL effectiveness against CTX-M-producing Gram-negative pathogens and essential details for further DBO design. Imipenem/REL remains an important choice for dealing with isolates co-producing CTX-M with other ß-lactamases.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Diverticulitis in Adults and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute diverticulitis. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Risk Assessment in Adults and Children.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides a recommendation for risk stratification according to severity of illness score. The panel's recommendation is based upon evidence derived from systematic literature reviews and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Utility of Intra-abdominal Fluid Cultures in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for obtaining cultures of intra-abdominal fluid in patients with known or suspected intra-abdominal infection. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Intra-abdominal Abscess in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute intra-abdominal abscess. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Appendicitis in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute appendicitis. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Cholecystitis and Acute Cholangitis in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute cholecystitis or acute cholangitis. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Utility of Blood Cultures in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for obtaining blood cultures in patients with known or suspected intra-abdominal infection. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Risk Assessment, Diagnostic Imaging, and Microbiological Evaluation in Adults, Children, and Pregnant People.

As the first part of an update to the clinical practice guideline on the diagnosis and management of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America, the panel presents twenty-one updated recommendations. These recommendations span risk assessment, diagnostic imaging, and microbiological evaluation. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

Comparison of available methods to evaluate cefiderocol susceptibility in Acinetobacter spp.

Recently, considerable uncertainty has arisen concerning the appropriate susceptibility testing for cefiderocol in gram-negative bacilli, particularly in the context of its application to Acinetobacter spp. The optimal method for assessing the susceptibility levels of Acinetobacter spp. to cefiderocol remains a subject of debate due to substantial disparities observed in the values obtained through various testing procedures. This study employed four minimum inhibitory concentration (MIC) methodologies and the disk diffusion to assess the susceptibility of twenty-seven carbapenem resistant (CR)-Acinetobacter strains to cefiderocol. The results from our study reveal significant variations in the minimum inhibitory concentration (MIC) values obtained with the different methods and in the level of agreement in interpretation categories between the different MIC methods and the disk diffusion test. Among the MIC methods, there was relatively more consistency in reporting the interpretation categories. For European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, the categorical agreement (CA) for MIC methods ranged between 66.7 and 81.5%. On the other hand, the essential agreement (EA) values were as low as 18.5-29.6%. The CA between MIC methods and disk diffusion was 81.5%. These results emphasize the need for a reliable, accurate, and clinically validated methodology to effectively assess the susceptibility of Acinetobacter spp. to cefiderocol. The wide variability observed in our study highlights the importance of standardizing the susceptibility testing process for cefiderocol to ensure consistent and reliable results for clinical decision-making.

Carbapenem-resistant Acinetobacter baumannii (CRAB): metabolic adaptation and transcriptional response to human urine (HU).

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major human pathogen and a research priority for developing new antimicrobial agents. CRAB is a causative agent of a variety of infections in different body sites. One of the manifestations is catheter-associated urinary tract infection, which exposes the bacteria to the host's urine, creating a particular environment. Exposure of two CRAB clinical isolates, AB5075 and AMA40, to human urine (HU) resulted in the differential expression levels of 264 and 455 genes, respectively, of which 112 were common to both strains. Genes within this group play roles in metabolic pathways such as phenylacetic acid (PAA) catabolism, the Hut system, the tricarboxylic acid (TCA) cycle, and other processes like quorum sensing and biofilm formation. These results indicate that the presence of HU induces numerous adaptive changes in gene expression of the infecting bacteria. These modifications presumably help bacteria establish and thrive in the hostile conditions in the urinary tract. These analyses advance our understanding of CRAB's metabolic adaptations to human fluids, as well as expanding knowledge on bacterial responses to distinct human fluids containing different concentrations of human serum albumin (HSA).

Lacticaseibacillus rhamnosus CRL 2244 secreted metabolites display killing and antibiotic synergistic activity against multi-drug resistant pathogens.

A growing increase in the number of serious infections caused by multidrug resistant bacteria (MDR) is challenging our society. Despite efforts to discover novel therapeutic options, few antibiotics targeting MDR have been approved by the Food and Drug Administration (FDA). Lactic acid bacteria have emerged as a promising therapeutic alternative due to their demonstrated ability to combat MDR pathogens in vitro. Our previous co-culture studies showed Lacticaseibacillus rhamnosus CRL 2244 as having a potent killing effect against carbapenem-resistant Acinetobacter baumannii (CRAB) strains. Here we report that cell-free conditioned media (CFCM) samples obtained from Lcb. rhamnosus CRL 2244 cultures incubated at different times display antimicrobial activity against 43 different pathogens, including CRAB, methicillin-resistant Staphylococcus aureus (MRSA) and carbapenemase Klebsiella pneumoniae (KPC)-positive strains. Furthermore, transwell and ultrafiltration analyses together with physical and chemical/biochemical tests showed that Lcb. rhamnosus CRL 2244 secretes a <3 kDa metabolite(s) whose antimicrobial activity is not significantly impaired by mild changes in pH, temperature and various enzymatic treatments. Furthermore, sensitivity and time-kill assays showed that the bactericidal activity of the Lcb. rhamnosus CRL 2244 metabolite(s) enhances the activity of some current FDA approved antibiotics. We hypothesize that this observation could be due to the effects of Lcb. rhamnosus CRL 2244 metabolite(s) on cell morphology and the enhanced transcriptional expression of genes coding for the phenylacetate (PAA) and histidine catabolic Hut pathways, metal acquisition and biofilm formation, all of which are associated with bacterial virulence. Interestingly, the extracellular presence of Lcb. rhamnosus CRL 2244 induced the transcription of the gene coding for the CidA/LgrA protein, which is involved in programmed cell death in some bacteria. Overall, the findings presented in this report underscore the promising potential of the compound(s) released by Lcb. rhamnosus CRL2244 as an alternative and/or complementary option to treat infections caused by A. baumannii as well as other MDR bacterial pathogens.

Determinants of COVID-19 Vaccine Hesitancy: A Cross-Sectional Study in Three Communities in the United States and Lebanon.

The COVID-19 pandemic underscores the significance of vaccine hesitancy in shaping vaccination outcomes. Understanding the factors underpinning COVID-19 vaccination hesitancy is crucial for tailoring effective vaccination strategies. This cross-sectional study, conducted in three communities across the United States and Lebanon, employed surveys to assess respondents' knowledge, attitudes, and perceptions regarding COVID-19 infection and vaccination. Among the 7196 participants, comprising 6775 from the US and 422 from Lebanon, vaccine hesitancy rates were comparable at 12.2% and 12.8%, respectively. Notably, a substantial proportion of respondents harbored misconceptions, such as attributing the potential to alter DNA (86.4%) or track individuals (92.8%) to COVID-19 vaccines and believing in the virus's artificial origins (81%). US participants had more misconceptions about the COVID-19 vaccine, such as altering DNA or causing infertility. Lebanese participants were more likely to question the origins of the virus and the speed of vaccine development. Additionally, US respondents were less worried about infection, while Lebanese respondents were more indecisive but less likely to outright reject the vaccine. Primary determinants of hesitancy included perceptions that the vaccine poses a greater risk than the infection itself (aOR = 8.7 and 9.4, respectively) and negative recommendations from healthcare providers (aOR = 6.5 and 5.4, respectively). Conversely, positive endorsements from healthcare providers were associated with reduced hesitancy (aOR = 0.02 and 0.4, respectively). Targeting healthcare providers to dispel misinformation and elucidate COVID-19 vaccine risks holds promise for enhancing vaccination uptake.

Synergistic effects of sulopenem in combination with cefuroxime or durlobactam against Mycobacterium abscessus.

Mycobacterium abscessus (Mab) affects patients with immunosuppression or underlying structural lung diseases such as cystic fibrosis (CF). Additionally, Mab poses clinical challenges due to its resistance to multiple antibiotics. Herein, we investigated the synergistic effect of dual ß-lactams [sulopenem and cefuroxime (CXM)] or the combination of sulopenem and CXM with ß-lactamase inhibitors [BLIs-avibactam (AVI) or durlobactam (DUR)]. The sulopenem-CXM combination yielded low minimum inhibitory concentration (MIC) values for 54 clinical Mab isolates and ATCC19977 (MIC50 and MIC90 ≤0.25 µg/mL). Similar synergistic effects were observed in time-kill studies conducted at concentrations achievable in clinical settings. Sulopenem-CXM outperformed monotherapy, yielding ~1.5 Log10 CFU/mL reduction during 10 days. Addition of BLIs enhanced this antibacterial effect, resulting in an additional reduction of CFUs (~3 Log10 for sulopenem-CXM and AVI and ~4 Log10 for sulopenem-DUR). Exploration of the potential mechanisms of the synergy focused on their interactions with L,D-transpeptidases (Ldts; LdtMab1-LdtMab4), penicillin-binding-protein B (PBP B), and D,D-carboxypeptidase (DDC). Acyl complexes, identified via mass spectrometry analysis, demonstrated the binding of sulopenem with LdtMab2-LdtMab4, DDC, and PBP B and CXM with LdtMab2 and PBP B. Molecular docking and mass spectrometry data suggest the formation of a covalent adduct between sulopenem and LdtMab2 after the nucleophilic attack of the cysteine residue at the ß-lactam carbonyl carbon, leading to the cleavage of the ß-lactam ring and the establishment of a thioester bond linking the LdtMab2 with sulopenem. In conclusion, we demonstrated the biochemical basis of the synergy of sulopenem-CXM with or without BLIs. These findings potentially broaden the selection of oral therapeutic agents to combat Mab. IMPORTANCE: Treating infections from Mycobacterium abscessus (Mab), particularly those resistant to common antibiotics like macrolides, is notoriously difficult, akin to a never-ending struggle for healthcare providers. The rate of treatment failure is even higher than that seen with multidrug-resistant tuberculosis. The role of combination ß-lactams in inhibiting L,D-transpeptidation, the major peptidoglycan crosslink reaction in Mab, is an area of intense investigation, and clinicians have utilized this approach in the treatment of macrolide-resistant Mab, with reports showing clinical success. In our study, we found that cefuroxime and sulopenem, when used together, display a significant synergistic effect. If this promising result seen in lab settings, translates well into real-world clinical effectiveness, it could revolutionize current treatment methods. This combination could either replace the need for more complex intravenous medications or serve as a "step down" to an oral medication regimen. Such a shift would be much easier for patients to manage, enhancing their comfort and likelihood of sticking to the treatment plan, which could lead to better outcomes in tackling these tough infections. Our research delved into how these drugs inhibit cell wall synthesis, examined time-kill data and binding studies, and provided a scientific basis for the observed synergy in cell-based assays.

Dual ß-lactam for treatment of pulmonary Mycobacterium abscessus in a child.

Treatment of Mycobacterium abscessus infection presents significant challenges, exacerbated by the emergence of macrolide-resistant strains that necessitate the use of multiple antimicrobials in combination and carry the potential for significant toxic effects. Select dual beta-lactam combinations, with or without beta-lactamase inhibitors, have been shown to be highly active in vitro. Herein, we describe a 6-year-old child with underlying mild bilateral lower lobe cylindrical bronchiectatic lung disease who developed pulmonary Mycobacterium abscessus infection and was treated with a multi-drug regimen including two ß-lactam antibiotics, achieving both early clinical and microbiological cure. This case highlights the potential benefit of dual ß-lactam therapy for the treatment of drug-resistant Mycobacterium abscessus infection.

First report of KPC variants conferring ceftazidime-avibactam resistance in Colombia: introducing KPC-197.

Resistance to ceftazidime-avibactam (CZA) due to Klebsiella pneumoniae carbapenemase (KPC) variants is increasing worldwide. We characterized two CZA-resistant clinical Klebsiella pneumoniae strains by antimicrobial susceptibility test, conjugation assays, and WGS. Isolates belonged to ST258 and ST45, and produced a KPC-31 and a novel variant KPC-197, respectively. The novel KPC variant presents a deletion of two amino acids on the Ω-loop (del_168-169_EL) and an insertion of two amino acids in position 274 (Ins_274_DS). Continued surveillance of KPC variants conferring CZA resistance in Colombia is warranted. IMPORTANCE: Latin America and the Caribbean is an endemic region for carbapenemases. Increasingly high rates of Klebsiella pneumoniae carbapenemase (KPC) have established ceftazidime-avibactam (CZA) as an essential antimicrobial for the treatment of infections due to MDR Gram-negative pathogens. Although other countries in the region have reported the emergence of CZA-resistant KPC variants, this is the first description of such enzymes in Colombia. This finding warrants active surveillance, as dissemination of these variants could have devastating public health consequences.