Ceftazidime-avibactam (CAZ-AVI) is a novel synthetic β-lactamase inhibitor combination. Although the combination has been available clinically for only a few years, cases of resistance to CAZ-AVI have already been reported. In the present review, we summarized the distribution of CAZ-AVI-resistant strains and the possible resistance mechanisms. There are no significant differences in CAZ-AVI resistance rates across different regions. CAZ-AVI maintains good activity against Gram-negative bacteria, especially Enterobacteriaceae. Pseudomonas aeruginosa is less susceptible to CAZ-AVI compared with Enterobacteriaceae, with a resistance rate ranging from 2.9% to 18%. The resistance to CAZ-AVI exceeds 50% in Acinetobacter baumannii. Higher resistance rate to CAZ-AVI is associated with carbapenem resistance. Moreover, β-lactamase related amino acid substitutions are the main mechanism leading to CAZ-AVI resistance. Membrane protein amino acid substitutions and efflux pumps also play important roles in CAZ-AVI resistance. In order to maintain its efficacy, CAZ-AVI should not be used for pathogens that are naturally resistant to it. For CAZ-AVI-resistant strains, other effective antibacterial agents or CAZ-AVI in combination with other antibacterial agents should be considered.

Single antimicrobial therapy has been unable to resist the global spread of bacterial resistance. Literatures of availablein vitroandin vivostudies were reviewed and the results showed that low frequency ultrasound (LFU) has a promising synergistic bactericidal effect with antibiotics against both planktonic and biofilm bacteria. It also can facilitate the release of antibiotics from medical implants. As a noninvasive and targeted therapy, LFU has great potential in treating bacterial infections. However, more in-depth and detailed studies are still needed before LFU is officially applied as a combination therapy in the field of anti-infective treatment.

Treatment of multidrug-resistant (MDR) Gram-negative bacteria (GNB) infections has led to a global public health challenging due to the bacterial resistance and limited choices of antibiotics. Cefiderocol (CFDC), a novel siderophore cephalosporin possessed unique drug delivery systems and stability to β-lactamases, has the potential to become first-line therapy for most aggressive MDR Gram-negative pathogens infection. However, there have been reports of drug resistance in the course of using CFDC. This study provides an overview of the in-vitro and in-vivo activity of CFDC and potential resistance mechanism was also summarized. In general, CFDC shows excellent activity against a broad range of MDR GNB pathogens including Enterobacteriaceae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. The expressions of metallo-β-lactamases such as inosine 5'-monophosphate (IMP), Verona integron-mediated metallo-β-lactamase (VIM), and New Delhi metallo-β-lactamase (NDM) are associated with a higher resistance rate of CFDC. Carbapenem-resistant phenotype has little effect on the resistance rate, although the acquisition of a particular carbapenemase may affect the susceptibility of the pathogens to CFDC. For potential resistance mechanism, mutations in β-lactamases and TonB-dependent receptors, which assist CFDC entering bacteria, would increase a minimum inhibitory concentration (MIC)90 value of CFDC against MDR pathogens. Since the development of CFDC, resistance during its utilization has been reported thus, prudent clinical applications are still necessary to preserve the activity of CFDC.

Background: Use of tigecycline in treating MDR Acinetobacter baumannii (MDRAB) remains controversial.Objectives: To comprehensively assess the safety and efficacy of tigecycline in pneumonia caused by Acinetobacter baumannii.Methods: PubMed, Embase, Web of Science and Cochrane library databases were searched up to 12 March 2019. Studies were included if they compared tigecycline-based regimens with other antibiotic regimens for treating AB pulmonary infections and we pooled the clinical outcomes, microbiological response, adverse events or mortality.Results: One prospective study and nine retrospective studies were included in this meta-analysis. The results showed similar clinical cure rates (OR = 1.04, 95% CI = 0.60–1.81; P = 0.89) and mortality rates (OR = 1.11, 95% CI = 0.65–1.89; P = 0.71) comparing tigecycline groups with the control groups. However, a significantly lower microbiological eradication rate was found in the tigecycline groups (OR = 0.43, 95% CI = 0.27–0.66; P = 0.0001). Incidence of nephrotoxicity in tigecycline-based regimens was significantly lower than in colistin-based regimens (OR = 0.34, 95% CI = 0.16–0.74, I2 = 35%, P = 0.006). There were no randomized controlled trials (RCTs) included; incomplete safety data and regional bias caused by the majority of the studies originating in China are the main limitations of this meta-analysis.Conclusions: Tigecycline can be used for treating MDRAB pulmonary infections owing to efficacy similar to that of other antibiotics. Moreover, tigecycline did not show a higher risk of mortality. Considering the lower microbiological eradication rate for tigecycline, which is likely to induce antimicrobial resistance, well-designed RCTs for high-dose tigecycline in treating pneumonia caused by AB are still needed.