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 β-lactamase-producing Enterobacterales (ESBL-E), AmpC β- 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..

Question 3.4: What Are the Preferred Antibiotics for the Treatment of Infections Outside of the Urinary Tract Caused by CRE if KPC Production is Present?

Suggested approach: Meropenem-vaborbactam, ceftazidimeavibactam, and imipenem-cilastatin-relebactam are preferred treatment options for KPC-producing Enterobacterales infections. Cefiderocol is an alternative options.

Although all 3 are preferred agents for the treatment of KPC-producing infections, the panel slightly favors meropenem-vaborbactam, followed by ceftazidime-avibactam, and then imipenem-cilastatin-relebactam, based on available data regarding clinical outcomes

Question 3.7: What Is the Likelihood of the Emergence of Resistance of CRE Isolates to the Newer β-Lactam Agents When Used to Treat CRE Infections?

Suggested approach: The emergence of resistance is a concern with all β-lactam agents used to treat CRE infections. Available data suggest the frequency may be highest for ceftazidime-avibactam.

Estimates of the emergence of resistance after clinical exposure to ceftazidime-avibactam and meropenem-vaborbactam are approximately 10%–20% and <5% respectively. if a patient was recently treated with ceftazidime-avibactam and presents with a sepsis-like condition, it is suggested to consider a different novel ß-lactam agent at least until culture and AST data are available.

Authors characterized the molecular determinants of meropenem–vaborbactam (MEV) non-susceptibility among non-metallo-β-lactamase-producing KPC-Klebsiella pneumoniae (KPC-KP). Whole-genome sequencing was performed to identify mutations associated with MEV non-susceptibility. Isolates with elevated MEV MICs were found to have mutations encoding truncated or altered OmpK36 porins and increased blaKPC copy numbers. KPC-KP isolates with decreased susceptibility to MEV were detected among a collection of isolates predating the availability of MEV

Meropenem-vaborbactam (MEV) is approved for the treatment of complicated intra-abdominal infections, hospital-acquired or ventilator-associated pneumonia and Gram-negative infections not responding to other treatments. There is limited data regarding its safety and efficacy in pwCF. The aim of this study was to describe the authors experience in pwCF attending a large UK CF centre.

This study aimed to elucidate the resistance mechanisms and assess the combined synergistic and bactericidal activities of aztreonam in combination with ceftazidime/avibactam (CZA), meropenem/vaborbactam (MEV), and imipenem/relebactam (IMR) against Enterobacterales strains producing dual carbapenemases. In vitro synergistic and bactericidal activities of the combination of aztreonam with CZA, MEV and IMR against these strains were determined using checkerboard assay and time-kill curve assay. A total of 12 Enterobacterales strains producing dual-carbapenemases were collected, including nine K. pneumoniae, two P. rettgeri, and one E. hormaechei. The most common dual-carbapenemase gene pattern observed was bla _{(KPC-2+NDM-5)} (n=4), followed by bla _KPC-2+IMP-26 (n=3), bla _{(KPC-2+NDM-1)} (n=2), bla _{(KPC-2+IMP-4)} (n=1), bla _{(NDM-1+IMP-4)} (n=1) and bla _{(KPC-2+KPC-2)} (n=1). The results of the checkerboard synergy analysis consistently revealed good synergistic effects of the combination of ATM with CZA, MEV and IMR.

The Authors determined whether the addition of vaborbactam, a second-generation β-lactamase inhibitor belonging to the boronate family, improves the activity of β-lactams against M. abscessus. The activity of β-lactams, alone or in combination with vaborbactam, was evaluated against M. abscessus CIP104536 by determining MICs, time-killing and intramacrophage activity. Kinetic parameters for the inhibition of BlaMab by vaborbactam were determined by spectrophotometry. The combination of vaborbactam (8 mg/L) with β-lactams decreased more than 8 times the MIC of amoxicillin (from >1024 to 128 mg/L) and 2 times the MICs of meropenem (from 16 to 8 mg/L) and imipenem (from 4 to 2 mg/L). In vitro and intracellularly, M. abscessus was not killed by the meropenem/vaborbactam combination, in spite of significant in vitro inhibition of BlaMab by vaborbactam. Inhibition of BlaMab by vaborbactam decreases the MIC of β-lactams, including that of meropenem. As meropenem/vaborbactam is clinically available, this combination offers an alternative therapeutic option that should be evaluated for the treatment of pulmonary infections due to M. abscessus

This metanalysis summarizes the available data on the efficacy and safety regarding the combination of meropenem-vaborbactam (MEV) versus the best available therapy (BAT). A total of four published studies were involved: one retrospective cohort study and three phase 3 trials, including 432 patients treated with MEV and 426 patients treated with BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, colistin, and tigecycline; or ceftazidime-avibactam; or piperacillin-tazobactam).  No significant difference in the clinical response rate was observed between MEBand the comparators at the test of cure (RR = 1.29, 95%CI [0.92, 1.80], p = 0.14) and end of treatment (RR = 1.66, 95%CI [0.58, 4.76], p = 0.34) visits. MEV was associated with a similar microbiological response as the comparators at TOC (RR = 1.63, 95%CI [0.85, 3.11], p = 0.14) and EOT assessment (RR = 1.16, 95%CI [0.88, 1.54], p = 0.14). In the pooled analysis of the four studies, 28-day all-cause mortality was lower for MEV than the control groups (RR = 0.47, 95%CI [0.24, 0.92], p = 0.03). MEV was associated with a similar risk of adverse events (AEs) as comparators (RR = 0.79, 95%CI [0.53, 1.17], p = 0.23). Additionally, MEV was associated with fewer renal-related AEs than the comparators (RR = 0.32, 95%CI [0.15, 0.66], p = 0.002). MEV was associated with a similar risk of treatment discontinuation due to AEs (RR = 0.76, 95%CI [0.38, 1.49], p = 0.42) or drug-related AEs (RR = 0.56, 95%CI [0.28, 1.10], p = 0.09) as the comparators. MEV presents a promising therapeutic option for treating CRE infections, demonstrating similar clinical and microbiological responses as other comparators, with potential advantages in mortality outcomes and renal-related AEs.

The aim of this study was to develop a test for rapid identification of susceptibility/resistance to ceftazidime/avibactam (CZA), Meropenem/vaborbactam (MEV), imipenem/relebactam (IPR), and cefiderocol (FDC) for Enterobacterales in a single test for rapid clinical decision making. MultiRapid ATB NP test is based on the detection of glucose metabolism occurring after bacterial growth in the presence of defined concentrations of CZA, MEV, IPR, and FDC, followed by visual detection of colour change of the pH indicator red phenol (red to yellow) generated by the acidification of the medium upon bacterial growth. The MultiRapid ATB NP test displayed 97.0% (confidence interval [CI] 92.6-98.8) sensitivity, 97.7% (CI 94.3-99.1) specificity, and 97.4% (CI 95.0-98.7) accuracy. The results were obtained after 3 h of incubation at 35 °C ± 2 °C, representing at least a 15-h gain-of-time compared with currently used antimicrobial susceptibility testing methods. The MultiRapid ATB NP test provided accurate results for the concomitant detection of susceptibility/resistance to CZA, MEV, IPR, and FDC in Enterobacterales, independent of the resistance mechanism.

Variable outcomes have been reported with cefiderocol (CFDC) in infections due to carbapenem-resistant Acinetobacter baumannii (CRAB). Nonetheless, it may be the only option for metallo-beta-lactamase-producing strains. Authors describe an outbreak of NDM-CRAB infections treated with CFDC. Thirty-eight patients were colonized and/or infected. Thirteen patients developed a systemic infection. A clinical cure was achieved in 10 (83%) patients, one VAP and 9 BSIs, at day 7. In vitro, the activity of CFDC does not appear to match in vivo effectiveness using currently available commercial tests. Despite high clinical cures, overall mortality remains high in severely ill patients. CFDC may be considered in this specific setting, though the implementation of susceptibility tests and infection control measures is mandatory.

Aztreonam (ATM) in combination with avibactam (AVI) has shown potential for treating MBL-producing carbapenem-resistant Enterobacterales (CREs) and Stenotrophomonas maltophilia. However, data on ATM in combination with other β-lactamase inhibitors (BLIs) are limited. We performed a multicenter study to evaluate the in vitro activities of ATM in combination with AVI, vaborbactam (VAB), relebactam (REL), tazobactam (TAZ) as well as with their commercially available formulations against CREs and S. maltophilia using broth microdilution. AVI restored ATM activity for MBL-producing CREs (ATM: 9.8% vs ATM-AVI: 78.0%) and S. maltophilia (ATM: 0% vs ATM-AVI: 93.3%). REL also moderately restored activity of ATM in MBL-producing CREs (ATM: 9.8% vs ATM-REL: 42.7%) and S. maltophilia (ATM: 0% vs ATM-REL: 68.9%). VAB and TAZ demonstrated very limited effect on the activity of ATM against CR-GNB evaluated. The combination of ATM with ceftazidime-AVI (CAZ-AVI) demonstrated maximum activity against CREs. Although ATM-CAZ-AVI is the most potent regimen available for CREs and S. maltophilia, ATM-IMI-REL might be a reasonable alternative.

This study evaluated the Vitek® RevealTM (VR) system for rapid antimicrobial susceptibility testing (AST) with 72 cases of monomicrobial BCs (55 Enterobacterales, 12 P. aeruginosa and 5 A. baumannii), including isolates producing carbapenemases and/or extended-spectrum β-lactamases. VR returned AST results with a mean TAT of 5.4 hours. Compared to a conventional workflow based on broth microdilution, VR exhibited essential agreement (EA) and category agreement (CA) >90% in most cases, except with meropenem for Enterobacterales (CA, 85.5%), piperacillin/tazobactam for P. aeruginosa (EA, 83.3%), and trimethoprim/sulfamethoxazole for A. baumannii (CA and EA, 80%). Bias exhibited an underestimation trend with ceftazidime/avibactam (-78.9%) and ceftazidime (-50%) for Enterobacterales and P. aeruginosa, respectively. Overall, VR appears an interesting tool to decrease TAT of the BC workflow, although further evaluation with some antibiotic-pathogen combinations would be warranted.

More and more ceftazidime-avibactam resistant KPC-producing K. pneumoniae have been reported with its widespread use, and the detection rate of KPC variants, has increased dramatically. However, the evolutionary mechanism and fitness effects during KPC mutation remained unknown. This article reports complex in vivo evolutionary trajectories of two novel KPC variants, KPC-155 (L169P/GT242A) and KPC-185 (D179Y/GT242A), from K.pneumoniae in the same patient. The novel variants were shown to confer ceftazidime-avibactam resistance but restore carbapenem susceptibility based on the results of plasmid transformation assays, cloning experiments, and enzyme kinetic measurements. The dynamic changes in blaKPC configuration highlight the need for consistent monitoring including antimicrobial susceptibility testing and determination of blaKPC subtypes-during clinical treatment, especially when ceftazidime-avibactam is administered.

Carbapenem-resistant Enterobacteriaceae infections are a considerable challenge for clinicians. In recent years, novel antibiotic options have resulted in a tremendous advance in medical therapy; however, current treatment options are primarily effective for resistance derived from serine-based carbapenemases. The Ambler class B metallo-β-lactamases (MBLs) remain a critical challenge with decidedly fewer effective options. One intriguing option for these MBL pathogens is the combination of ceftazidime-avibactam with aztreonam. While clinical experience with this regimen is limited, in vitro studies are promising, and limited case reports describe success with this regimen; however, significant challenges preclude widespread adoption of this novel treatment regimen. A systemic literature review was performed to offer recommendations based on current evidence for a practical strategy on how to best integrate the use of aztreonam with avibactam combination therapy.

This research focused on evaluating the clinical results of patients suffering from pneumonia caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), who received treatment with either ceftazidime-avibactam (CAZ-AVI) alone or in combination with other antibiotics. In total, 195 CRKP-related pneumonia patients treated in two Chinese tertiary hospitals were retrospectively analyzed. Among them 103 (52.8 %) received CAZ-AVI combination therapy, and 92 (47.2 %) patients received CAZ-AVI monotherapy. The combination therapy group exhibited superior clinical and microbiological cure rates compared to the monotherapy group, with a 14-day clinical cure rate of 60.1 % vs. 45.7 % (P = 0.042) and a 14-day microbiological cure rate of 72.8 % vs. 58.6 % (P = 0.038), respectively. Combination therapy reduced mortality rates at 14 days (7.8 % vs. 17.4 %, P = 0.041), but not at 30 days (14.6 % vs. 25.0 %, P = 0.066).  This finding indicates that patients with pneumonia due to CRKP benefit from combination treatment of CAZ-AVI rather than monotherapy; administering carbapenem in combination with CAZ-AVI in the early stages could provide considerable survival benefits.

To monitor the resistance rate and gain a deeper understanding of the resistance mechanisms, a 2-year surveillance was conducted focusing on the Klebsiella pneumoniae associated with the clinical usage of ceftazidime-avibactam (CZA) in a teaching hospital. A total of 4,641 K. pneumoniae isolates were screened to identify the CZA resistance through antimicrobial susceptibility testing. In total, four CZA-resistant K. pneumoniae (CZA-R-Kp) strains were separated from four patients, in which three of them received CZA treatment during the hospitalization, accounting for a 4% (3/75) resistance development rate of K. pneumoniae under CZA stress. All CZA-R-Kp isolates were found to possess variants of blaKPC-2. The identified mutations included blaKPC-33, blaKPC-86, and a novel variant designated as blaKPC-129, all of which were located in the Ω loop of the KPC enzyme. These mutations were found to impact the amino acid sequence and spatial structure of the enzyme’s active centre, consequently affecting KPC carbapenemase activity. This study underscores the importance of active surveillance to monitor the emergence of resistance to CZA, highlighting the need for ongoing research to develop effective strategies for combating antimicrobial resistance. Understanding the mechanisms behind resistance is crucial in maintaining the efficacy of CZA, a vital tool in the battle against multidrug-resistant infections.

Bloodstream infections (BSIs) due to multidrug-resistant Gram-negative bacteria (MDR-GNB) pose a significant global health threat amid rising antimicrobial resistance (AMR). This study aimed to investigate the efficacy of ceftazidime-avibactam (CZA) as a therapeutic option for these infections, addressing the urgent need for novel treatments. In a department of Microbiology in India, 147 multidrug-resistant (MDR) organisms were identified from a total of 376 positive blood cultures, and 100 were randomly selected for final analysis. Klebsiella pneumoniae (K. pneumoniae) was the predominant (78%) organism among the subsets, with varying susceptibility patterns observed across species. The overall CZA susceptibility was 45%, with significant discrepancies between disk diffusion and gold standard testing. This study underscores the pressing need for reliable testing methods and novel treatment strategies in combating MDR infections. Further research with larger sample sizes is imperative to validate our findings and guide clinicians effectively in addressing this critical health challenge.

Cefiderocol (CFDC) antibacterial activity against normally susceptible species is not affected by most β-lactamases, including metallo-β-lactamases. Due to the siderophore-mediated entry into the cell, its activity is less affected by porin loss or active efflux resistance than many other β-lactam antibiotics. The aim of this study was to assess in vitro susceptibility to the CFD of carbapenemase-producing gram-negative bacilli from clinical samples of hospitalized patients. Authors analysed 102 clinical strains of carbapenemase-producing Enterobacterales and non-fermentives from hospital centers in Łódź, Poland. Antimicrobial susceptibility to CFD was tested by the minimum inhibitory concentration test strips and disc diffusion methods. The obtained results turned out to be ambiguous, and the area of technical uncertainty made their interpretation very difficult. The cost of therapy with this antibiotic, and difficulties in interpreting the drug susceptibility are the limitations to the use of CFDC. Intensive work should be carried out to finally standardize an easily accessible and reliable method for the determination of susceptibility to CFDC.

Carbapenemase gene acquisition can limit their spectrum of activity, and reports of resistance toward these new molecules are increasing. In this multi-center study, we evaluated the prevalence of resistance to ceftazidime-avibactam (CZA) and comparators among P. aeruginosa clinical isolates from bloodstream infections, hospital-acquired or ventilator-associated pneumonia, and urinary tract infections, circulating in Southern Italy. A total of 120 P. aeruginosa isolates were collected. CZA was among the most active β-lactams, retaining susceptibility in the 81.7% of cases, preceded by cefiderocol (95.8%) and followed by ceftolozane-tazobactam (79.2%), meropenem-vaborbactam (76.1%), imipenem-relebactam (75%), and aztreonam (69.6%). CZA represents a highly active antipseudomonal β-lactam compound (after cefiderocol), and that metallo-β-lactamases (VIM-type) and extended-spectrum β-lactamases (GES and PER-type) production is the major factor underlying CZA resistance in isolates from Southern Italian hospitals.

Abdominal aortic graft infection (AGI) is a rare but life-threatening disease. The diagnosis is based on clinical manifestations, laboratory tests, and imaging studies. Surgical removal of the infected graft is the cornerstone of AGI. However, in some conditions, especially for patients with a short life expectancy and high surgical risk, conservative treatment with life-long or longtime antimicrobial therapy is the only reasonable option. The antibiotic therapy represents a key issue when dealing with AGI, due to the polymicrobial nature of the infection and especially the formation of biofilm on the prosthetic graft, so that antibiotics targeting the biofilm should be chosen to eradicate the infection, particularly when the graft is not explanted. Here we describe a case of a woman with an abdominal aortic graft infection who was managed with long-term conservative antimicrobial therapy and at the end treated with Delafloxacin, due to the adverse effects and partial failure of other antibiotics, and the documented potency and efficacy of this new fluoroquinolone against biofilms. The patient is well more than 1 year following presentation with no signs of ongoing graft infection.

This study compared the in vitro activity of delafloxacin with other fluoroquinolones against bacterial pathogens recovered from inpatients with osteomyelitis n total, 100 bacterial isolates (58 % Gram-negative and 42 % Gram-positive) recovered from inpatients between January and April 2021, were reidentified at species level by MALDI-TOF MS. Results showed that delafloxacin exhibited greater in vitro potency (at least 64-times) than the other tested fluoroquinolones (levofloxacin and ciprofloxacin) when evaluating Staphylococcus aureus (MIC50 ≤0.008 mg/L) and coagulase-negative Staphylococcus (MIC50 0.06 mg/L). Furthermore, delafloxacin (MIC50 0.25 mg/L) was at least 4 times more potent than other tested fluoroquinolones (MIC50 1 mg/L) against P. aeruginosa. Delafloxacin also exhibited a strong activity (71.4 %‒85.7 %.) against biofilm producing bacterial pathogens tested in this study. Interestingly, 82.14 % of the staphylococci tested in this study harbored mecA gene. In addition, the gyrA and parC genes in fluoroquinolone-resistant Gram-negative isolates displayed different mutations (substitutions and deletions). Delafloxacin was the most active fluoroquinolone against staphylococci (including MRSA) and P. aeruginosa when compared to other fluoroquinolones such as ciprofloxacin and levofloxacin.

The study aimed to estimate epidemiological cut-off (ECOFF) values and to identify mutations in the gyrA gene, specific to FQ resistance, without increasing the MICs of delafloxacin, in 231 clinical strains of H. pilori, collected in the bacteriology laboratory of Poitiers University Hospital over a 2 year period. From them,  101 clinical strains with an levofloxacin-resistant phenotype (MIC > 1 mg/L) were selected from 2018 to 2022 for delafloxacin MIC determination and QRDR (gyrA) sequencing. The estimated ECOFF of delafloxacin was ≤0.125 mg/L. No H. pylori isolate showed a levofloxacin-sensitive phenotype with a delafloxacin MIC of >0.125 mg/L. Among the levofloxacin-resistant H. pylori isolates, 53.5% had delafloxacin MICs of ≤0.125 mg/L. The N87I mutation was associated with dual levofloxacin/delafloxacin resistance (P < 0.001) in contrast to the N87K and D91N mutations (P > 0.05). Mutations D91G and D91Y were not associated with a delafloxacin resistance phenotype (P > 0.05). Delafloxacin seems to be a therapeutic alternative for levofloxacin-resistant strains with greater in vitro activity.

Susceptibility of delafloxacin on 199 osteoarticular levofloxacin-resistant staphylococci strains was reported in 49% and 1% using SSTI S. aureus breakpoint (0.25 mg/L) and general S. aureus breakpoint (0.016 mg/L) respectively. Fifty percents levofloxacin-resistant staphylococci showed resistance to delafloxacin using CA-SFM/EUCAST recommendations.

A qualitative survey was conducted in March 2022 including sixteen infectiologists, one internist, five hospital pharmacists, and one pharmacologist, to identify the current practices with long half-life lipoglycopeptides (LGPs) and potential use/position of oritavancin. Despite their indication being limited to skin and soft tissue infections (SSTIs), long half-life lipoglycopeptides are mainly used off-label to treat bone and joint infections (BJIs) and infective endocarditis. Due to its shorter half-life, oritavancin might have an advantage over dalbavancin for a treatment duration of less than 2 weeks, as it could be used both in prolonged treatments of complicated patients in BJIs or administered as a single-dose treatment for Gram-positive cocci infections usually treated with a 5 to 10 day antibiotic course. Oritavancin strengthens the therapeutic arsenal in numerous infections from BJIs to urinary tract infections and could help to manage specific clinical situations, on top of providing potential benefits for the hospital’s budget.

Oritavancin(ORI) and dalbavancin (DBV) are long-acting lipoglycopeptide antibiotics approved for the treatment of skin and skin structure infections. Recently, they have been used for outpatient antimicrobial therapy for complicated infections. Aim of this single-centre, retrospective cohort study was to compare outcomes of patients treated with multiple doses of ORI or DBV for complicated infections, evaluating adult patients who received two or more doses of lipoglycopeptides for complicated infections from Feb. 2019 through to Dec. 2022. Patients receiving ORI were compared to DBV after propensity score-matching with the primary endpoint that was clinical success at 90 days. 131 matched pairs (N = 262) were included in the analysis. Most patients were receiving lipoglycopeptide therapy for osteomyelitis. There was no significant difference in efficacy between multi-dose ORI and DBV for the treatment of complicated infections. Both agents were generally well tolerated; however, dalbavancin may be better tolerated when long-term treatment is warranted.

The authors reported a case of a man in his eighties with a late shoulder prosthetic joint infection (PJI) caused by methicillin resistant Staphyloccus epidermidis with contraindications for surgical replacement and few oral therapeutic options for a long term suppressive antibiotic therapy. The prosthesis was retained, and the patient received ten outpatient sequential doses of 1200 mg of oritavancin during 28 weeks, based on therapeutic drug monitoring as a guide for correct timing of administration of each dose. During oritavancin administration, the patient achieved clinical cure, with disappearance of the pain and regaining pre-infection joint mobility, with no side effects reported and no further surgery or hospitalization needed. The treatment is ongoing as a long-lasting suppressive antimicrobial therapy. Oritavancin could represent an excellent solution for treating PJI caused by methicillin resistant organism, especially in patients who need a long-term suppressive therapy.

Dalbavancin (DBV), has linear dose-related PK allowing a prolonged interval between doses. This retrospective analysis study in patients with cardiovascular infection (infective endocarditis, bacteremia, implantable electronic device infection), treated with DBV at Hospital Clínico S. Carlos (Madrid) for 7 years (2016–2022). Patients were divided in two study groups: 1) Infective endocarditis (IE); 2) Bacteremia. Total 25 patients were treated with DBV for cardiovascular infection and IE was the most common indication (68%), followed by bacteremia (32%) with male predominance in both groups (64% vs 62%) and median age of 67,7 and 57,5 years, respectively. 100% of blood cultures were positive to Gram-positive microorganisms (Staphylococcus spp., Streptococcus spp. or Enterococcus spp.) in both study groups. Previously to DBV, all patients received other antibiotic therapy, both in the group of IE as in bacteremia. The main reason for the administration of DBV was to continue IV antimicrobial therapy outside the hospital in both the IE group (n = 15) and the bacteremia group (n = 8). DBV was used as consolidation therapy in a once- or twice-weekly regimen. Microbiological and clinical successes were reached in 84% of cases (n = 21), 76,4% in IE group and 100% in bacteremia group.

A systematic review  was conducted to describe the clinical efficacy and the safety of dalbavancin in infective endocarditis treatment. Nine observational study were included. Five out of nine studies documented a clinical failure rate of less than 10%. Dalbavancin showed a favourable safety profile.  Dalbavancin appears to be a promising option for the consolidation therapy of infective endocarditis.

Dalbavancin is a long-acting lipoglycopeptide that shows promise for off-label use in adults given its unique pharmacokinetics and in vitro potency against common Gram-positive isolates; however, evidence to support its use in children is limited. This publication reports the use  of dalbavancin in three pediatric cases in patients aged 17 months of age, 3 years of age, and 11 years of age. All infections were caused by S. aureus (66.7% methicillin-resistant S. aureus) representing varied disease, including an osteoarticular infection and catheter-related bloodstream infection. Following the utilization of Dalbavancin, high clinical success and low rates of adverse effects were observed with high patients’ and parents’ satisfaction.

This study explores resistance development and mechanisms in MRSA isolates, especially after the first dalbavancin-resistant MRSA strain in our hospital in 2016. This study investigated 55 MRSA bloodstream isolates (02/2015-02/2021) from the University Hospital of the Medical University of Vienna, Austria.  S.aureus BSI strain 19-362 had two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene  Isolate 16-33 had a 534 bp deletion in the DHH domain of GdpP and a SNV in pbp2 (p.G146R). Transmission electronic microscopy revealed significantly thicker cell walls in 16-33 (p < 0.05) compared to 19-362 and dalbavancin-susceptible strains. Two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene were newly identified as possible causes of dalbavancin resistance.