The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasing in recent years. Chinese Infectious Disease Surveillance of Pediatrics (ISPED) showed that in 2022, its resistance rate to meropenem was 18.5%. However, there is limited data available on the treatment of CRKP infection in neonates. In this study, we present a case involving a premature infant infected with OXA-48-producing Klebsiella pneumoniae. The combined susceptibility test revealed a significant synergistic effect between ceftazidime-avibactam(CAZ-AVI), and aztreonam(ATM). The infection was successfully treated with a combination of CAZ-AVI, ATM, and fosfomycin. This case represents the first reported instance of sepsis in a premature infant caused by OXA-48-producing Klebsiella pneumoniae in China. The objective of our study is to evaluate the effectiveness and safety of combination therapy in treating CRKP infections in premature infants. We hope that the findings of this study will provide valuable insights for clinicians in their treatment approach.

UNASSIGNED: Carbapenem-resistant Enterobacterales (CRE) due to Metallo-β-lactamase (MBL) production are treated with either polymyxins or the novel combination of ceftazidime-avibactam and aztreonam (AA). This study aims to evaluate the 30-day mortality of AA in patients with BSI caused by MBL-CRE infections.
UNASSIGNED: In this systematic review and meta-analysis, all articles up to June 2023 were screened using search terms like \'CRE\', \'MBL\', \'AA\' and \'polymyxins\'. The risk ratio for AA vs polymyxins was pooled using a random-effect model, and the results were represented by a point estimate with a 95% confidence interval.
UNASSIGNED: After removing the duplicates, the titles and abstracts of 455 articles were screened, followed by a full-text screening of 50 articles. A total of 24 articles were included for systematic review, and four comparative studies were included in the meta-analysis. All four studies had a moderate or serious risk of bias. The pooled risk ratio for 30-day mortality for AA vs. polymyxins was 0.51 (95%CI: 0.34-0.76), p < 0.001. There was no significant heterogeneity.
UNASSIGNED: The meta-analysis from studies with a high risk of bias shows that AA is associated with lesser 30-day mortality when compared to polymyxins in patients with MBL-producing CRE BSI. Registration with PROSPERO- CRD42023433608.

Objective: To describe the impact of pharmacy driven penicillin allergy assessments on de-labeling penicillin allergies and antibiotic streamlining opportunities for hospitalized patients. Design: Multi-center, retrospective case-series study. Setting: A health system of 4 non-teaching hospitals. Participants: Patients aged 18 years and older with a physician order for a pharmacist penicillin allergy assessment. Exclusion criteria consisted of patients with anaphylaxis or a type II penicillin allergy, anaphylaxis of any cause within 4 weeks, refusal of penicillin allergy skin test (PAST), antihistamine use within 24 hours, penicillin intolerance, immunosuppression or immunosuppressive medications, or skin conditions that could interfere with PAST. Interventions: The primary endpoint evaluated the number of de-labeled penicillin allergies after pharmacists provided penicillin allergy assessments. Secondary endpoints evaluated the percent of patients with antibiotics deescalated to beta-lactam antibiotics and classification of notable interventions made by pharmacists. Measurements and Main Results: There were 35 patients who met inclusion criteria. Twenty-four patients underwent both penicillin allergy skin testing and oral (PO) amoxicillin challenge. Five patients had allergies de-labeled only after a pharmacist interview. Four patients received only the PO amoxicillin challenge and 2 patients received only PAST. Penicillin allergies were de-labeled from the electronic health record (EHR) in 31 (89%) patients despite all testing negative for a penicillin allergy from PAST or a PO amoxicillin challenge. Four patients had the allergy re-added to the chart on subsequent admissions. No patients experienced a reaction from PAST, PO amoxicillin challenge, or subsequent beta-lactam antibiotics. Twenty-eight (80%) patients had their antibiotic therapy changed as a result of the allergy assessment. Seventeen patients were de-escalated onto beta-lactam antibiotics and aztreonam was stopped in 6 patients. Conclusion: Results from this study suggests that pharmacists expanding their scope of practice with PAST is a safe and effective allergy de-labeling tool. Pharmacist-driven penicillin allergy assessments could provide antibiotic cost savings and avoid aztreonam use. The study supports the need to emphasize education for patients and caretakers regarding allergy testing results to avoid relabeling in future hospital visits.

OBJECTIVE: The aim of this study was to describe our experience of a combination treatment including meropenem/vaborbactam (M/V) plus aztreonam (ATM) for bloodstream infections (BSIs) due to ceftazidime/avibactam-resistant Klebsiella pneumoniae (CAZ/AVI-R-Kp), for which gene typing was not available at the time the blood culture (BC) results were obtained.
METHODS: Between 20 July and 22 August 2021, in our hospital laboratory, the molecular test for carbapenemase gene typing was not available. All Gram-negative bloodstream infections were recorded, and characteristics of patients were analysed. Among them, three patients had positive BCs for CAZ/AVI-R-Kp, and the empirical therapy was switched to M/V plus ATM pending phenotypic testing of sensitivity to M/V. Therapy was subsequently targeted on the basis of the results of this test.
RESULTS: KPC and NDM represent the most prevalent carbapenemases in our polyclinic. Three patients with CAZ/AVI-R-Kp sepsis were treated with M/V plus ATM not knowing the carbapenemase gene. Two had an NDM-Kp infection for which, upon obtaining the result of sensitivity to M/V, combination therapy was maintained. The third had KPC-Kp infection for which ATM was discontinued, after the acquisition of an antibiogram reporting full sensitivity to M/V (MIC = 0.25 mg/L). One patient with NDM-Kp infection died due to complications of the underlying disease for which he was hospitalised.
CONCLUSIONS: Meropenem/vaborbactam plus ATM and subsequent de-escalation could represent a possible therapeutic strategy in severe CAZ/AVI-R-Kp infections when carbapenemase gene typing is not rapidly available.

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.

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat in both solid organ and stem cell transplant recipients. Invasive CPE infections in transplant recipients are associated with a high mortality, often due to limited therapeutic options and antibacterial toxicities. One of the most therapeutically challenging group of CPE are the metallo-β-lactamase (MBL)-producing Gram-negative bacteria, which are now found worldwide, and often need treatment with older, highly toxic antimicrobial regimens. Newer β-lactamase inhibitors such as avibactam have well-established activity against certain carbapenemases such as Klebsiella pneumoniae carbapenemases (KPC), but have no activity against MBL-producing organisms. Conversely, aztreonam has activity against MBL-producing organisms but is often inactivated by other co-existing β-lactamases. Here, we report four cases of invasive MBL-CPE infections in transplant recipients caused by IMP-4-producing Enterobacter cloacae who were successfully treated with a new, mechanism-driven antimicrobial combination of ceftazidime/avibactam with aztreonam. This novel antimicrobial combination offers a useful treatment option for high-risk patients with CPE infection, with reduced drug interactions and toxicity.

Ceftriaxone is the only consistently active antimicrobial agent recommended for the treatment of Neisseria gonorrhoeae. Although some new antimicrobials are in development, the necessity to expand treatment options in the near term may require using older drugs that have not been widely used to treat gonorrhoea.
We conducted a literature review of clinical trials and case series, published from 1983 to 2017, reporting treatment efficacy results following administration of 1 g aztreonam intramuscularly or IV for uncomplicated gonococcal infections. We summed trial data, stratified by anatomical site of infection, and calculated summary efficacy estimates and 95% CI for each site of infection.
The 10 identified clinical trials enrolled 678, 38 and 16 individuals with urogenital, rectal and pharyngeal gonorrhoea, respectively. Aztreonam had an efficacy of 98.6% (95% CI: 97.5%-99.4%) for urogenital, 94.7% (95% CI: 82.3%-99.4%) for rectal and 81.3% (95% CI: 54.4%-96.0%) for pharyngeal gonococcal infections.
Although most clinical trials included in this meta-analysis were conducted >30 years ago, aztreonam appears to have excellent efficacy for urogenital gonorrhoea; its efficacy at extragenital sites remains uncertain.

To provide an update on efficacy and safety of antibiotic treatments for stable non-cystic fibrosis (CF) bronchiectasis (BE). Systematic review based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was done. Twenty-six studies (1.898 patients) fulfilled the inclusion criteria. Studies of inhaled tobramycin have revealed conflicting results regarding quality of life (QoL), exacerbations and admissions, but may result in sputum cultures negative for Pseudomonas aeruginosa, whereas studies investigating the effect of inhaled gentamycin have shown positive effects on sputum bacterial density, decrease in sputum cultures positive for P. aeruginosa, QoL and exacerbation rate, but no improvement in forced expiratory volume in first second (FEV1). Oral azithromycin can reduce exacerbations, together with minor improvements in QoL and FEV1. Furthermore, oral erythromycin reduces exacerbations, but has no effect on lung function, symptoms or QoL. Inhaled ciprofloxacin may reduce P. aeruginosa in sputum cultures, but without changes in lung function, exacerbations or QoL. Although with limited evidence, inhaled colistin may have effects on P. aeruginosa density, exacerbations and QoL, whereas studies on aztreonam revealed no significant clinical improvements in the outcomes of interest, including exacerbation rate. Adverse events, including bronchospasm, have been reported in association with tobramycin and aztreonam. Several antibiotic treatment regimens have been shown to improve QoL and exacerbation rate, whereas findings regarding sputum production, lung function and admissions have been conflicting. Evidence-based treatment algorithms for antibiotic treatment of stable non-CF BE will have to await large-scale, long-term controlled studies.

The monobactam aztreonam is currently being re-examined as a therapeutic agent in light of the global spread of carbapenem resistance in aerobic Gram-negative bacilli and aztreonam\'s stability to Ambler class B metallo-β-lactamases. Of particular interest are the pharmacokinetic and pharmacodynamic properties of aztreonam alone and in combination with β-lactamase inhibitors. The choice of inhibitor may vary depending on the spectrum of β-lactamases produced by Enterobacteriaceae. The monobactam ring is also being used to produce new developmental monobactams. Thus, a greater understanding of aztreonam pharmacokinetics and dynamics is of great relevance in drug development. This review summarizes the pharmacokinetic profile of aztreonam in man and its pharmacodynamics in human and pre-clinical studies when studied alone and with β-lactamase inhibitors.

BACKGROUND: Chronic airway infection in cystic fibrosis (CF) is linked with progressive loss of pulmonary function and is the primary cause of mortality. Treatment regimens have generally focused on the use of chronic antibiotic therapy to target Pseudomonas aeruginosa (PA), a major pathogen associated with a decline in FEV1%. Specifically, inhaled antibiotic therapy provides high antibiotic sputum concentrations and decreases bacterial burden.
METHODS: This article describes the pharmacology, pharmacodynamics/pharmacokinetics, clinical efficacy, microbiology and safety of aztreonam lysine (AZLI, Cayston), an inhaled antibiotic indicated for use in CF patients with PA. Articles were identified using MEDLINE (1966 - June 13, 2013) and EMBASE (1947 - June 13, 2013). Abstracts from the annual meeting (2011 - 2012) of the North American Cystic Fibrosis Conference were searched to identify additional publications.
CONCLUSIONS: AZLI is an additional product that can be used in the management of CF and will likely play a major role in the suppression of PA. Clinical trials have demonstrated improvements in pulmonary function and patient reported symptoms. AZLI may therefore be used as an alternative to traditional inhaled antibiotics in patients with moderate-to-severe CF and PA colonization. Further investigation is warranted into use of AZLI in mild lung disease and for PA eradication.