Successful rescue treatment of sepsis due to a pandrug-resistant, NDM-producing Klebsiella pneumoniae using aztreonam powder for nebulizer solution as intravenous therapy in combination with ceftazidime/avibactam

Sieswerda, Elske; Brand, Marre van den; Berg, Roland B van den; Sträter, Joris; Schouls, Leo M.; Dijk, Karin van; Budding, Andries E.

doi:10.1093/jac/dkz495

Cited by 25 publications

(11 citation statements)

References 7 publications

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“…The relative majority (7 out of 18) were conducted in the US [ 50 , 51 , 52 , 56 , 57 , 62 , 65 ]. The remaining were performed in the following countries: France (3), Italy (3), Australia (1), Greece (1), Mexico (1), Netherlands (1), Saudi Arabia (1), Spain (1) [ 4 , 47 , 53 , 54 , 55 , 58 , 59 , 60 , 61 , 63 , 64 ]. All of them were case reports/case series, barring two different cohorts (one retrospective, another prospective) of patients from Italy and Greece affected by NDM-producing isolates [ 4 , 47 ].…”

Section: Resultsmentioning

confidence: 99%

“…With regard to clinical efficacy, clinical resolution within 30 days was achieved in almost four-fifths of patients (80%, 75/94). Early recurrence was described in four cases [ 56 , 58 , 64 ]: notably, in three patients [ 58 , 64 ], the same treatment was re-administered, obtaining resolution of infection except in a single subject expired owing to chronic lung transplant rejection [ 58 ]. In the case series by Shah and colleagues, two late recurrences (within 90 days of follow-up) were described as well [ 56 ], and another late recurrence (at 4-month of follow-up) was described in the other case series [ 61 ].…”

Section: Resultsmentioning

confidence: 99%

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The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases

et al. 2021

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Infections caused by metallo-β-lactamase (MBL)-producing Enterobacterales and Pseudomonas are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither standard therapy nor consensus for the management of these infections exist. Aztreonam, an old β-lactam antibiotic, is not hydrolyzed by MBLs. However, since many MBL-producing strains co-produce enzymes that could hydrolyze aztreonam (e.g., AmpC, ESBL), a robust β-lactamase inhibitor such as avibactam could be given as a partner drug. We performed a systematic review including 35 in vitro and 18 in vivo studies on the combination aztreonam + avibactam for infections sustained by MBL-producing Gram-negatives. In vitro data on 2209 Gram-negatives were available, showing the high antimicrobial activity of aztreonam (MIC ≤ 4 mg/L when combined with avibactam) in 80% of MBL-producing Enterobacterales, 85% of Stenotrophomonas and 6% of MBL-producing Pseudomonas. Clinical data were available for 94 patients: 83% of them had bloodstream infections. Clinical resolution within 30 days was reported in 80% of infected patients. Analyzing only patients with bloodstream infections (64 patients), death occurred in 19% of patients treated with aztreonam + ceftazidime/avibactam. The combination aztreonam + avibactam appears to be a promising option against MBL-producing bacteria (especially Enterobacterales, much less for Pseudomonas) while waiting for new antimicrobials.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases

et al. 2021

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“…The observation that PBP3 insertions and CMY-42 production in E. coli could adversely impact ATM-AVI activity against MBLs-producing Enterobacteriaceae (MPE) reveals a clinically significant spectrum gap in this MBL-targeted therapy. Such vulnerability of ATM-AVI could also compromise the combined effectiveness of CAZ-AVI and ATM (both targeting PBP3), being viewed as a “rescue therapy” for serious MBL-producer infections ( 43 , 44 ).…”

Section: Discussionmentioning

confidence: 99%

Differences in the Distribution of Species, Carbapenemases, Sequence Types, Antimicrobial Heteroresistance and Mortality Rates Between Pediatric and Adult Carbapenemase-Producing Enterobacterales in Bloodstream Infections

Liu

et al. 2022

Front. Med.

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The dissemination of carbapenemase-producing Enterobacterales (CPE) is worrisome given their scarce treatment options. CPE bloodstream infections (BSIs) had a high mortality rate in adults, and there was little data on pediatric CPE-BSIs around the world. We comprehensively explored the differences in the clinical and microbiological characteristics between pediatric and adult CPE-BSIs. Forty-eight pediatric and 78 adult CPE-BSIs cases were collected. All-cause 30 day-mortality in children with CPE-BSIs (14.6%, 7/48) was significantly lower than that in adult patients (42.3%, 33/78, p = 0.001). The subgroup in adults empirically treated with tigecycline as an active drug displayed a significantly higher 30-days crude mortality (63.3%, 19/30) than the subgroup treated without tigecycline (29.2%, 14/48, p = 0.003). K. pneumoniae was the most prevalent species in both the pediatric (45.8%, 22/48) and adult populations (64.1%, 50/78), with discrepant carbapenemase genes in each population: 95.4% (21/22) of the pediatric K. pneumoniae isolates carried blaNDM, while 82.0% (41/50) of the adult strains harbored blaKPC. The ratio of E. coli in children (37.5%) was significantly higher than that in adults (12.8%, p = 0.002). In both populations, the majority of E. coli expressed blaNDM, particularly blaNDM−5. With statistical significance, blaNDM was much more common in children (95.8%, 46/48) than in adults (34.6%, 27/78). The rate of multiple-heteroresistance phenotypes in children was as high as 87.5%, which was much lower in adults (57.1%). Agar dilution checkboard experiment against one pediatric carbapenemase-producing E. coli isolates showed that the combination of amikacin and fosfomycin yielded an additive effect. Overall, K. pneumoniae was the most common CPE-BSIs pathogen in both populations, with NDM-producing K. pneumoniae and KPC-producing ST11 K. pneumoniae being the most prevalent species in children and adults, respectively. E. coli was more prevalent in children than in adults, yet blaNDM−5 was the most common carbapenem-resistant mechanism in E. coli in both populations. The wide range of multiple-heteroresistance combination traits found in different pathogen species from different host populations should provide a good foundation for future combination therapy design. Further investigations from more CPE isolates of various species are needed to evaluate the possible in vitro partial synergy of the amikacin and fosfomycin combination.

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“…If third-generation cephalosporin-resistant Enterobacteriaceae is isolated (production of ESBLs or cephamycinases), treatment can be done with carbapenems or ceftazidime-avibactam. In the case of carbapenemresistant Enterobacteriaceae (generally by the production of carbapenemases), treatment can be performed with ceftazidime-avibactam [108] or, in the case of metallo-βlactamases, with the association of ceftazidime-avibactam with aztreonam [109][110][111] or with cefiderocol (if available) or with colistin as last option. If P. aeruginosa is isolated, the treatment is selected according to its susceptibility pattern, giving preference to the most active β-lactam in vitro (lower MIC) and with the lower risk of selection for resistant mutants.…”

Section: Recommendations For the Selection Of Antibiotic Treatmentmentioning

confidence: 99%

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2021

Rev Esp Quimioter

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Successful rescue treatment of sepsis due to a pandrug-resistant, NDM-producing Klebsiella pneumoniae using aztreonam powder for nebulizer solution as intravenous therapy in combination with ceftazidime/avibactam

Cited by 25 publications

References 7 publications

The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases

The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases

Differences in the Distribution of Species, Carbapenemases, Sequence Types, Antimicrobial Heteroresistance and Mortality Rates Between Pediatric and Adult Carbapenemase-Producing Enterobacterales in Bloodstream Infections

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