Ceftazidime/Avibactam-Resistant Klebsiella pneumoniae subsp. pneumoniae Isolates in a Tertiary Italian Hospital: Identification of a New Mutation of the Carbapenemase Type 3 (KPC-3) Gene Conferring Ceftazidime/Avibactam Resistance

Fontana, Carla; Favaro, Marco; Campogiani, Laura; Malagnino, Vincenzo; Minelli, Silvia; Bossa, Maria Cristina; Altieri, Anna; Andreoni, Massimo; Sarmati, Loredana

doi:10.3390/microorganisms9112356

Cited by 12 publications

(9 citation statements)

References 34 publications

(54 reference statements)

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“…In favor of our result, an Italian study attributed the emergence of CZA resistance to bla KPC expression in 57.1% of the analyzed K. pneumoniae isolates. 37 In addition, Liao and others reported the development of CZA resistance in a CRKP clinical isolate secondary to bla KPC-78 ; a new bla KPC-2 variant induced by point mutation following CZA therapy. 38 …”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms Mediating Ceftazidime/Avibactam Resistance Amongst Carbapenem-Resistant Klebsiella pneumoniae Isolates from Cancer Patients

El-Kady¹,

Elbaiomy²,

Elnagar³

2022

IDR

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Background A growing body of evidence suggests that ceftazidime/avibactam (CZA) is a potential therapeutic option for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections; however, resistant strains are increasingly emerged worldwide. Herein, we deemed to investigate the susceptibility profile of CRKP isolates from cancer patients to CZA and to identify the underlying resistance mechanisms. Methods Clinical samples were obtained from adult patients admitted to the Oncology Center of Mansoura University, Mansoura, Egypt. The antibiotic susceptibility pattern of K. pneumonia e isolates to different antibiotics was tested by the modified Kirby Bauer’s disc diffusion method. Minimum inhibitory concentrations of CZA were assessed using broth microdilution method. Screening for carbapenemase-producing strains was achieved by the modified Hodge test. Multiplex polymerase chain reactions (PCRs) were conducted for uncovering of carbapenemase-encoding genes ( bla KPC , bla VIM , bla IMP , bla NDM-1 , and bla OXA-48 ), and outer membrane porin genes ( ompK35 and ompK36 ). Results A total of 12 CZA-resistant isolates were identified out of 47 CRKP isolates (25.5%). The MIC 50 and MIC 90 of CZA against CRKP were 1 and 64 µg/mL, respectively. Risk factors for CZA resistance included chronic kidney disease, mechanical ventilation, longer length of hospital stay, and ICU admission. The multivariate logistic regression demonstrated that longer length of hospital stay ( P =0.03) was the only independent predictor for acquisition of CZA-resistant isolates. The leading mechanism for CZA resistance was sustained by bla KPC (50%), meanwhile 16.7% and 8.3% of the CZA-resistant isolates harbored bla OXA-48 and bla OXA-48 / bla NDM-1 , respectively. The MBL-encoding genes bla NDM-1 and bla IMP were detected in 16.7% and 8.3% of the isolates, respectively. Absence of both ompK35 and ompK36 was observed in 58.3% of the CZA-resistant isolates. Conclusion CZA has displayed superior in vitro activity against CRKP isolates in comparison to other antibiotics; however, thorough molecular characterization of resistant strains is highly recommended in future studies to detect and monitor the emergence of further tackling strains.

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Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms Mediating Ceftazidime/Avibactam Resistance Amongst Carbapenem-Resistant Klebsiella pneumoniae Isolates from Cancer Patients

El-Kady¹,

Elbaiomy²,

Elnagar³

2022

IDR

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“…In the present study, only 15.6% of CAZ-AVI-R strains were not detected as KPC-producing by immunocromatographic assays (5 out of 33). Genetic characterization of the strains was performed in four isolates, and the data have been recently published [29]. The strains were all KPC-3, with D179Y substitutions in the Ω-loop; meropenem susceptibility was restored in all the isolates previously resistant to carbapenemes, and none of the strains were detected as KPC by immunocromatographic assay [29].…”

Section: [S] + 4 [I]mentioning

confidence: 99%

“…Genetic characterization of the strains was performed in four isolates, and the data have been recently published [29]. The strains were all KPC-3, with D179Y substitutions in the Ω-loop; meropenem susceptibility was restored in all the isolates previously resistant to carbapenemes, and none of the strains were detected as KPC by immunocromatographic assay [29]. The identification of risk factors for the development of CAZ-AVI resistance could help select target populations in which to use specific molecular assays, genotypic testing, and phenotypic resistance profiles, changing CAZ-AVI-R K. pneumoniae infections management and outcome and allowing better antibiotic tailoring.…”

Section: [S] + 4 [I]mentioning

confidence: 99%

Resistance to Ceftazidime/Avibactam in Klebsiella pneumoniae KPC-Producing Isolates: A Real-Life Observational Study

et al. 2023

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Background: Ceftazidime/avibactam (CAZ-AVI) resistance amongst Enterobacterales is worryingly increasing worldwide. Objectives: The aim of this study was to collect and describe real-life data on CAZ-AVI-resistant Klebsiella pneumoniae (KP) isolates in our University Hospital, with the ultimate goal of evaluating possible risk factors related to the acquisition of resistance. Methods: This is a retrospective observational study, including unique Klebsiella pneumoniae (KP) isolates resistant to CAZ-AVI (CAZ-AVI-R) and producing only KPC, collected from July 2019 to August 2021 at Policlinico Tor Vergata, Rome, Italy. The pathogen’s list was obtained from the microbiology laboratory; clinical charts of the corresponding patients were reviewed to collect demographic and clinical data. Subjects treated as outpatients or hospitalized for <48 h were excluded. Patients were then divided into two groups: S group, if they had a prior isolate of CAZ-AVI-susceptible KP-KPC, and R group, if the first documented isolate of KP-KPC was resistant to CAZ-AVI. Results: Forty-six unique isolates corresponding to 46 patients were included in the study. The majority of patients (60.9%) were hospitalized in an intensive care unit, 32.6% in internal medicine wards and 6.5% in surgical wards. A total of 15 (32.6%) isolates were collected from rectal swabs, representing a colonization. Amongst clinically relevant infections, pneumonia and urinary tract infections were the most commonly found (5/46, 10.9% each). Half of the patients received CAZ-AVI prior to isolation of the KP-KPC CAZ-AVI-R (23/46). This percentage was significantly higher in patients in the S group compared to patients in the R group (69.3% S group vs. 25% R group, p = 0.003). No differences between the two groups were documented in the use of renal replacement therapy or in the infection site. The clinically relevant CAZ-AVI-R KP infections (22/46, 47.8%) were all treated with a combination therapy, 65% including colistin and 55% including CAZ-AVI, with an overall clinical success of 38.1%. Conclusions: Prior use of CAZ-AVI was associated with the emergence of drug resistance.

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“…CAZ-AVI also has activity against ceftazidime-resistant and certain carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa , but not strains producing metallo-beta-lactamases (MBLs) (Ambler class B) [ 5 ]. The proportion of isolates resistant to CAZ-AVI is relatively low, but emerges worldwide [ 6 , 7 , 8 , 9 , 10 ]. Bacterial resistance mechanisms, that could potentially affect CAZ-AVI, include mutant or acquired PBPs, decreased outer membrane permeability or active efflux to either compound, as well as b-lactamase enzymes being refractory to inhibition by avibactam and able to hydrolyze ceftazidime [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Off-Label Use of Ceftazidime/Avibactam for the Treatment of Pan-Drug-Resistant Klebsiella pneumoniae in a Neonate: Case Report and Literature Review

et al. 2023

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Background: Klebsiella pneumoniae is among the most common Gram-negative bacteria isolated to neonatal intensive care units (NICU) and one of the leading causes of morbidity and mortality. The ceftazidime/avibactam (CAZ-AVI) combination is approved for infections caused by aerobic Gram-negative organisms. It is licensed for use in infants over 3 months old. There are no safety and efficacy data regarding the administration of CAZ-AVI to infants younger than 3 months, except for a few case reports. Case presentation: This report describes a severely intoxicated 24-day-old, full-term, male neonate transferred to NICU level III from a secondary maternity hospital due to the deterioration of his general condition. On day four of admission, blood culture revealed the pan-drug-resistant (PDR) K. pneumoniae ss. pneumoniae, susceptible only to CAZ-AVI, which thus represented the only treatment option. Off-label CAZ-AVI was administered intravenously as a salvage therapy. Conclusions: In healthcare settings, treating resistant K. pneumoniae presents serious challenges, especially in NICU patients. The off-label treatment with CAZ-AVI for 17 days was safe and effective in this one-month-old patient. A year later, the patient was healthy with normal cognitive development.

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Ceftazidime/Avibactam-Resistant Klebsiella pneumoniae subsp. pneumoniae Isolates in a Tertiary Italian Hospital: Identification of a New Mutation of the Carbapenemase Type 3 (KPC-3) Gene Conferring Ceftazidime/Avibactam Resistance

Cited by 12 publications

References 34 publications

Molecular Mechanisms Mediating Ceftazidime/Avibactam Resistance Amongst Carbapenem-Resistant Klebsiella pneumoniae Isolates from Cancer Patients

Molecular Mechanisms Mediating Ceftazidime/Avibactam Resistance Amongst Carbapenem-Resistant Klebsiella pneumoniae Isolates from Cancer Patients

Resistance to Ceftazidime/Avibactam in Klebsiella pneumoniae KPC-Producing Isolates: A Real-Life Observational Study

Off-Label Use of Ceftazidime/Avibactam for the Treatment of Pan-Drug-Resistant Klebsiella pneumoniae in a Neonate: Case Report and Literature Review

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