PubMed · 3311617
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W R Outman. 1987. Aztreonam.. https://pubmed.ncbi.nlm.nih.gov/3311617/
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Metallo-β-lactamase-producing Enterobacterales are distributed worldwide, but some Latin American countries show a higher prevalence. Aztreonam-avibactam (ATM-AVI) may be an option for treating these infections. To evaluate in vitro susceptibility to aztreonam (ATM) alone and ATM-AVI in carbapenem-non-susceptible Enterobacterales isolates, based on the type of carbapenemase production, we prospectively collected carbapenem-non-susceptible Enterobacterales isolates from Peruvian hospitals during 2023-2024. Identification and susceptibility testing were performed by commercial panels and disk diffusion. Carbapenemases were detected by immunochromatography. ATM and ATM-AVI MICs were determined using broth microdilution panels with avibactam fixed at 4 µg/mL. The non-susceptible isolates to ATM-AVI and those with double production of carbapenemases underwent whole-genome sequencing. A total of 438 Enterobacterales isolates were analyzed; carbapenemase production was detected in 422 (96.3%) and NDM was the most frequent (61.9%). Coproduction of NDM + KPC in K. pneumoniae and NDM + OXA-48-like in Escherichia coli was observed. Overall, 99.3% were susceptible to ATM-AVI; MIC50 and MIC90 were 0.12 and 2 µg/mL, respectively. Overall, K. pneumoniae isolates had lower MIC50 and MIC90 values to ATM-AVI (0.12 and 0.5 µg/mL) compared to E. coli (0.5 and 4 µg/mL). Three E. coli isolates were resistant to ATM-AVI (MIC ≥ 8 µg/mL), they belonged to ST410, ST167, and ST10 and harbored a YRIN insertion in PBP3 along with CYM-type, PER-type, and CTX-M-type beta-lactamase genes. ATM-AVI demonstrated potent activity against carbapenem-non-susceptible Enterobacterales, including those producing NDM, which is the carbapenemase most frequently detected in Peruvian hospitals.IMPORTANCEEnterobacterales isolates cause common illnesses in humans. Carbapenems are the antibiotics used to treat several of these infections, and increasingly, isolates resistant to these antibiotics are found. The most important mechanism of resistance to carbapenem among Enterobacterales is the production of enzymes called carbapenemases. Our results allowed us to recognize that NDM is the most frequent type of carbapenemase detected. Most of the antimicrobials available do not cover the Enterobacterales carrying NDM carbapenemase. In this scenario, we found that the new combination of drugs, aztreonam-avibactam, has high in vitro efficacy against most of the carbapenem-resistant isolates and against those isolates carrying NDM carbapenemase.
OBJECTIVE: To evaluate whether resistance to third-generation cephalosporins and/or aztreonam was associated with a higher mortality rate among patients with nosocomial Klebsiella pneumoniae infections. DESIGN: Retrospective cohort study.Setting. Tertiary care university hospital. METHODS: A total of 143 patients with nosocomial infections due to K. pneumoniae were evaluated. Death within 21 days after diagnosis of infection was the outcome. Demographic data, invasive procedures, presence and severity of underlying conditions, infection diagnosis, anatomic site of isolation, and treatment of infection, as well as resistance to third-generation cephalosporins and/or aztreonam, were evaluated for association with the outcome. RESULTS: The mortality associated with nosocomial K. pneumoniae infections was 22% in our study. Drug resistance was found in isolates from 48% of case patients. Multivariate analysis demonstrated that the severity of the patient's underlying condition (odds ratio, 12.50; P<.01) and isolation of the microorganism from the blood or from another usually sterile site (odds ratio, 2.94; P=.03) were associated with death. On the other hand, the presence of resistance to cephalosporins and/or aztreonam did not affect mortality, and the use of inadequate treatment was not significantly associated with increased mortality. When only the severe cases of infection were analyzed, the results were unchanged. CONCLUSIONS: Resistance to cephalosporins and/or aztreonam did not affect mortality, and the use of inadequate treatment was not significantly associated with increased mortality. The reasons for this are not clear. It is possible that the severity of the underlying disease and the patient's condition have a larger role than the K. pneumoniae infection in determining the outcome, and initially inadequate treatment may not have an impact sufficient to cause irreversible damage, allowing treatment to be changed to an effective drug.
Multidrug resistance (MDR) has been reported in both prokaryotes and eukaryotes, underscoring the challenge of design and screening of more efficacious new drugs. For instance, the efflux pump of Pseudomonas aeruginosa (gram-negative bacteria) can extrude a variety of structurally and functionally diverse substrates, which leads to MDR. In this study, we present a new platform that studies modes of action of antibiotics in living bacterial cells (P. aeruginosa), in real-time, at nanometer scale and single-cell resolution using nanoparticle optics and single living cell imaging. The color index of silver (Ag) nanoparticles (violet, blue, green, and red) is used as the sized index (30 +/- 10, 50 +/- 10, 70 +/- 10, and 90 +/- 10 nm) for real-time measurement of sized transformation of the cell wall and membrane permeability at the nanometer scale. We have demonstrated that the number of Ag nanoparticles accumulated in cells increases as the aztreonam (AZT) concentration increases and as incubation time increases, showing that AZT induces the sized transformation of membrane permeability and the disruption of the cell wall. The results demonstrate that nanoparticle optics assay can be used as a new powerful tool for real-time characterization of modes of action of antimicrobial agents in living cells at the nanometer scale. Furthermore, studies of mutants of WT bacteria (nalB-1 and DeltaABM), suggest that an efflux pump (MexA-MexB-OprM) effectively extrudes substrates (nanoparticles) out of the cells, indicating that the MDR mechanism involves the induction of changes in membrane permeability and the intrinsic pump machinery.