Antimicrobial resistance

Since the 1990s, antimicrobial resistance (AMR) has escalated dramatically among Acinetobacter baumannii-calcoaceticus complex [ABC]). Global spread of multidrug-resistant (MDR)-ABC strains reflects dissemination of a few clones between hospitals, geographic regions, and continents; excessive antibiotic use amplifies this spread. Many isolates are resistant to all antimicrobials except colistimethate sodium and tetracyclines (minocycline or tigecycline); some infections are untreatable with existing antimicrobial agents. AMR poses a serious threat to effectively treat or prevent ABC infections. Strategies to curtail environmental colonization with MDR-ABC require aggressive infection-control efforts and cohorting of infected patients. Thoughtful antibiotic strategies are essential to limit the spread of MDR-ABC. Optimal therapy will likely require combination antimicrobial therapy with existing antibiotics as well as development of novel antibiotic classes 1).


Pyrinezolid (PZ), a novel oxazolidinone compound, can effectively inhibit most Gram-positive bacteria, including methicillin resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Though PZ is a promising antimicrobial candidate, the druggability of PZ is limited by its poor water solubility. Therefore, the amphipathic mPEG-PLLA copolymer was used to prepare the pyrinezolid micelles (PZ-M). Herein, we described the preparation, pharmacokinetic properties, tissue distribution, efficacy and toxicity of PZ-M. In vivo studies show that PZ-M possess prolonged blood circulation time and increased oral bioavailability compared with free PZ. Meanwhile, PZ-M increase lung PZ exposure and reduce liver and kidney exposure, which indicates that PZ-M may enhance the efficacy in vivo in MRSA-related pneumonia patients and decrease potential renal and hepatic toxicities 2).


Klebsiella pneumoniae has been reported to develop increased antimicrobial resistance. Ceftazidime-avibactam (CZA) is a novel antibiotic with activity against serine-lactamase. Chen et al. investigated the sensitivity of carbapenem-resistant K. pneumoniae (CRKP) to CZA and the mechanisms of drug resistance in our hospital.

Methods and results: Patient characteristics were obtained from medical records. Klebsiella pneumoniae and its antibiotic susceptibility were determined using the Vitek-2 Compact instrument. The antimicrobial resistance genes KPC, NDM, OXA-48, VIM, IMP, CIM, SPM, TMB, SMB, SIM, AIM, and DIM were detected using Real-Time PCR. Multilocus sequence typing was used for genetic RELATEDNESS analysis. In total, 121 CRKP strains were isolated from patients in the intensive care unit (51.2%), senior ward (12.4%), and neurosurgery department (10%). With an average age of 72.5 years, most patients were in care for respiratory (34.7%), brain (20.7%), digestive tract (13.2%), and cardiovascular (8.3%) diseases. Specimens were predominantly obtained from sputum (39.67%), urine (29.75%) and blood (6.61%).

Conclusion: Of 23 CZA-resistant CRKP strains (19.01%), ST11 being the most common at 56.52%, eleven NDM-1-positive (47.83%) and four NDM-5-positive (17.39%) strains were detected.

Significance and impact of study: Our study indicates that CZA resistance occurs in ~19.01% CRKP strains and that blaNDM-1 and blaNDM-5 might be critical for resistance 3).

1)
Lynch JP 3rd, Clark NM, Zhanel GG. Infections Due to Acinetobacter baumannii-calcoaceticus Complex: Escalation of Antimicrobial Resistance and Evolving Treatment Options. Semin Respir Crit Care Med. 2022 Feb;43(1):97-124. doi: 10.1055/s-0041-1741019. Epub 2022 Feb 16. PMID: 35172361.
2)
Long H, Li X, Sang Z, Mei L, Yang T, Li Z, Zhou L, Zheng Y, He G, Guo G, Wang Z, Deng Y, Luo Y. Improving the pharmacokinetics and tissue distribution of pyrinezolid by self-assembled polymeric micelles. Colloids Surf B Biointerfaces. 2017 May 8;156:149-156. doi: 10.1016/j.colsurfb.2017.05.014. [Epub ahead of print] PubMed PMID: 28527358.
3)
Chen D, Liying X, Hong D, Zhao Y, Hu X, Shi S, Chen F. Epidemiology of resistance of carbapenemase-producing Klebsiella pneumoniae to ceftazidime-avibactam in a Chinese hospital. J Appl Microbiol. 2021 May 30. doi: 10.1111/jam.15166. Epub ahead of print. PMID: 34053144.