Emergence of a KPC-90 Variant that Confers Resistance to Ceftazidime-Avibactam in an ST463 Carbapenem-Resistant Pseudomonas aeruginosa Strain

For the first time, we reported a KPC variant, KPC-90, in a clinical ST463 CRPA strain with CZA resistance. CZA resistance was mediated by a 2 amino acid insertion outside the KPC omega-loop region in CRPA.

Effects of sleeve gastrectomy versus omega-loop gastric bypass. What is best for weight loss, perioperative adverse events, and comorbidities?

Aim of the study: This study investigated whether Sleeve Gastrectomy (SG) or Omega-Loop-Gastric-Bypass (OAGB) has the best benefit in weight loss, perioperative risk, and remission of comorbidities. Methods: 29,407 patients after SG and OAGB were included in the German Bariatric Surgery Registry (GBSR). Outcome criteria were perioperative morbidity, perioperative complications, and remission of comorbidities after one year of follow-up. Results: 15,169 patients had completed 1-year follow-up (770 patients after OAGB and 14,399 after SG). The %EWL was higher for OAGB than for SG (70.4 ± 18.5 for OAGB and 62.4 ± 22.6 for SG; p<0.001). BMI reduction was also a significant difference in favor of OAGB (17.5 ± 5.6 kg/m2 for OAGB vs. 15.5 ± 5.9 for SG; p<0.001). There was no significant difference between the two groups in perioperative complications (p<5%). Significant differences in favor of OAGB were found in remission of hypertension (p<0.001), IDDM (p<0.001), NIDDM (p<0.001), reflux (p<0.001), and sleep apnea (p<0.001). Conclusion: Our analysis showed that OAGB surgery was associated with more significant BMI reduction and weight loss one year after surgery. In addition, OAGB surgery was significantly more effective in improving obesity-related comorbidities. Our results support the performance of OAGB over SG in patients with obesity and comorbidities. However, the contraindications and general condition of the patient should be considered in the context of this.

1285. Identification of KPC Omega Loop Variant R163S Conferring Ceftazidime-Avibactam Resistance

Background We report on a 56 year-old male with prolonged COVID-19 pneumonia who initially improved with dexamethasone and intubation but quickly decompensated. Clinical and radiologic features were consistent with VAP. Tracheal aspirate cultures grew carbapenem-resistant Enterobacter cloacae; meropenem (MEM) MIC was &gt;8 ug/ml (resistant) while ceftazidime-avibactam (CZA) MIC was 2/4 ug/ml (susceptible). Lateral flow antigen assay detected a KPC enzyme. The patient was treated with CZA with steady improvement in respiratory function over the next two weeks. He then experienced an episode of tachycardia, prompting repeat culture. At this point the patient had been extubated: sputum culture grew KPC+ E. cloacae that now showed CZA-resistance (MIC &gt;8/4 ug/ml) and paradoxical decrease in MEM MIC (4 ug/ml); meropenem-vaborbactam (&lt; 2/8 ug/ml) was susceptible. Methods The pre- & post-CZA therapy E. cloacae isolates underwent whole genome sequencing using the Illumina 150bp paired end protocol; sequences were quality trimmed and compared. Results A point mutation in the plasmid blaKPC3 gene was identified in the post-CZA therapy isolate, an R163S mutation in the omega loop of the enzyme. ompC and ompF porin genes were analyzed to rule-out decreased influx as a mechanism for CZA-resistance: the pre- and post-CZA isolates had identical porin sequences. Conclusion This case highlights emerging mutations within KPC carbapenemases that lead to resistance to ‘last-line’ antimicrobials like CZA. The presumptive mechanism is increased KPC active site promiscuity due to increased omega loop flexibility, allowing increased ceftazidime binding and hydrolysis, and decreased avibactam binding and beta lactamase inhibition. Paradoxically, MEM susceptibility improves after such omega loop mutations, likely due to decreased active site binding affinity, a ‘seesaw’ effect between MEM and CZA. While authors have reported MEM MICs falling into the ‘susceptible’ category after an omega loop variant, these bacteria invariably develop secondary mutations leading to MEM treatment failure. Fortunately, given our patient’s improved respiratory status, the post-CZA E. cloacae isolate was felt to reflect colonization and the patient was discharged home without antimicrobial therapy. Disclosures Romney Humphries, PhD D(ABMM), Accelerate Diagnostics (Individual(s) Involved: Self): Consultant, Shareholder; IHMA (Individual(s) Involved: Self): Consultant; Melinta (Individual(s) Involved: Self): Consultant; Momentum (Individual(s) Involved: Self): Grant/Research Support; Pattern (Individual(s) Involved: Self): Consultant; QPex (Individual(s) Involved: Self): Consultant; ThermoFisher (Individual(s) Involved: Self): Consultant; Torus (Individual(s) Involved: Self): Consultant

Emergence of a KPC Variant Conferring Resistance to Ceftazidime-Avibactam in a Widespread ST11 Carbapenem-Resistant Klebsiella pneumoniae Clone in China

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection poses a great threat to public health worldwide, and KPC-2-producing strains are the main factors responsible for resistance to carbapenems in China. Ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor combination with good activity against KPC-2 carbapenemase and is becoming the most important option for treating KPC-producing CRKP infection. Here, we report the emergence of a novel KPC-2 variant, designated KPC-74, produced by K. pneumoniae strain KP55, that conferred CZA resistance in a patient after CZA exposure. The novel blaKPC–74 variant showed a deletion of 6 nucleotides at positions 712–717 compared with blaKPC–2, and this deletion resulted in the consequent deletion of glycine and valine at positions 239 and 240. Antimicrobial susceptibility testing showed that KP55 presents multidrug resistance, including resistance to CZA and ertapenem, but is susceptible to imipenem, meropenem, and colistin. The blaKPC–74 gene was located on a plasmid, as determined by S1-nuclease pulsed-field gel electrophoresis followed by southern blotting, and confirmed to be 133,766 bp in length by whole-genome sequencing on both the Illumina and MinION platforms. The CZA resistance phenotype of the novel KPC variant was confirmed by both transformation of the blaKPC–74-harboring plasmid and a blaKPC–74 gene cloning assay, showing a 64-fold higher CZA minimum inhibitory concentration (MIC) than the recipient strains. The G239_V240del observed in KPC-74 was outside the omega-loop region but was still close to the active site Ser70 and omega-loop in the protein tertiary structure. The enzyme kinetic parameters and IC50 values further indicated that the hydrolytic activity of the KPC-74 enzyme against ceftazidime was potentiated twofold and that the affinity between KPC-74 and avibactam was alleviated 17-fold compared with that of the KPC-2 allele. This CZA resistance mediated by KPC-74 could be selected after CZA therapy and evolved to be more diverse and heterogeneous. Surveillance of CZA resistance is urgently needed in clinical settings.

Dentin Opaquer: A Pediatric Aesthetic Enhancement Technique

Introduction: Early childhood caries in young children can be initial dental caries and caries involving most of the tooth structure resulting in pulpal involvement causing loss of tooth structure. There is a need for tooth restoration for functional and aesthetic reasons. Dentine opaquer can be used to fulfill both the criteria. Aim: The aim was to determine the efficacy of dentine opaquer to mask the underlying color of caries treated with restorative material and omega metal post after pulpectomy. Methods: A report of 2 cases performed in the Department of Pediatric and Preventive Dentistry in, Krishnadevaraya College of Dental Sciences and Hospital Bangalore. Two different treatments using dentine opaquer as the restorative material and as core buildup over glass ionomer cement were performed. Results: Both the cases showed favorable outcomes and better masking efficiency of dentine opaquer as restorative material and core build up material over glass ionomer cement. Conclusions: Dentine opaquer is a composite with a compatible shade and better retention on the tooth surface, as core build up material and along with omega loop demonstrated adequate retention, was easy to administer as a chair side technique and resulted in least resistant masticatory forces.

Aktuelle Aspekte der Verfahrenswahl bei Adipositas-Chirurgie

ZusammenfassungDie Adipositas- bzw. metabolische Chirurgie stellt derzeit evidenzbasiert die einzige Therapiemodalität dar, die bei Patienten mit drittgradiger Adipositas zu einem nachhaltigen und auch klinisch relevanten Gewichtsverlust, zu einer Verbesserung der Lebensqualität und Funktionalität sowie zu einer Minderung vorliegender Adipositas-assoziierter Begleiterkrankungen und damit zu einer Verlängerung der Lebenserwartung führt.Die Operationen werden vorzugsweise in zertifizierten Zentren mit niedriger perioperativer Morbidität und Letalität in Schlüsselloch-Technik durchgeführt. Die weltweit am häufigsten durchgeführten adipositaschirurgischen Verfahren sind die Sleevegastrektomie (SG), der Roux-en-Y-Magenbypass (RYGB) und der Omega-Loop-Bypass (oder Mini-Gastric-Bypass) (MGB). Daneben existieren weitere intestinale Bypassverfahren.Die Entscheidung für das jeweilige Operationsverfahren ist im interdisziplinären Konsens von einem Team, bestehend aus Chirurgen, Internisten, Psychiatern/Psychologen und Ökotrophologen, individuell für jeden Patienten in Abhängigkeit der Komorbiditäten und patientenbezogener Daten zu treffen. Im Nachfolgenden werden die verschiedenen Operationsverfahren im Hinblick auf ihre jeweiligen Vor- und Nachteilen miteinander verglichen und auf die für das jeweilige Verfahren am besten geeignete Patientengruppe eingegangen.