Aztreonam, Ceftazidime/Avibactam, and Colistin Combination for the Management of Carbapenemase-Producing Klebsiella Pneumoniae Bacteremia: A Case Report

Abstract

Purpose: A case of a patient with sepsis from a urinary source due to carbapenemase-producing Klebsiella pneumoniae treated with a novel combination of aztreonam, ceftazidime/avibactam, and colistin is described. Summary: An 80-year-old South Asian male presented to the hospital with sepsis from a urinary source. Blood and urine cultures were positive for a carbapenemase-producing K pneumoniae sensitive only to colistin and tigecycline. Novel beta-lactamase inhibitor combinations ceftazidime/avibactam and meropenem/vaborbactam were resistant. Patient was initially on ceftazidime/avibactam and colistin combination followed by tigecycline and colistin with lack of improvement. Metallo-beta-lactamase (MBL)-producing K pneumoniae was suspected based on the sensitivity pattern and history of medical treatment in India. Patient was then initiated on novel combination of ceftazidime/avibactam, aztreonam, and colistin. Patient’s white blood cell (WBC) count and fever curve normalized. Unfortunately, the patient failed to recover completely likely because of his multiple comorbidities and declining functional status, resulting in the family’s decision to pursue hospice. Conclusion: The combination of ceftazidime/avibactam and aztreonam should be considered as a viable treatment option for patients with infections caused by MBL-producing Enterobacteriaceae.

Therapeutic Options for Metallo-β-Lactamase-Producing Enterobacterales

“…The current available clinical data are limited to observational studies including various case reports and one prospective study to support its efficacy. 29,49,[57][58][59][60][61] In the lone prospective observational study, Falcone et al compared outcomes for 102 patients with bloodstream infections caused by MBL-producing Enterobacterales receiving either CAZ-AVI plus ATM or another active antibiotic. The most common causative organism was K. pneumoniae (91.2%) and only NDM (80.4%) and VIM (19.6%) were detected among all patients enrolled in the study.…”

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

“…Of the remaining 90 studies, 37 were excluded due to the reasons listed in Figure 2 , wherein the entire process of article selection is illustrated. Overall, 35 in vitro studies [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ] and 18 in vivo studies [ 4 , 47 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , …”

“…A total of 18 studies were retrieved addressing the clinical use of ATM plus CZA against MBL-producers, whose general features are detailed in Table 3 . 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 ].…”

“…The combination of CZA and ATM was administered as targeted therapy in nearly all cases (99%, 93/94), namely after demonstration of the synergistic activity of the association of the drugs, inactive when considered singularly. The only exception was a case of BSI by a presumptive MBL-producing strain: carbapenemase was not detected but suspicion was raised in light of medical history (previous treatments in India) and of the susceptibility profile of the K. pneumoniae isolate, but synergism was not demonstrated between CZA and ATM [ 56 ]. Outcomes’ definitions were quite heterogeneous.…”

“…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 ].…”