Evidence map›Paper›PMID 27594850›Full record

ArticleFrontiers in microbiology2016

Tracking Cefoperazone/Sulbactam Resistance Development In vivo in A. baumannii Isolated from a Patient with Hospital-Acquired Pneumonia by Whole-Genome Sequencing.

Xiaofen Liu, Huajun Zheng, Weipeng Zhang, Zhen Shen, Miao Zhao, Yuancheng Chen, Li Sun, Jun Shi, Jing Zhang

Open access · goldAbstract read
In one paragraph

Article in Frontiers in microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Evolution of cefoperazone-sulbactam consumption in Romania between 2011 and 2024.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
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  2. Alteration ofMicrobiology spectrum · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Xiaofen LiuInstitute of Antibiotics, Huashan Hospital, Fudan UniversityShanghai, China; Roche Innovation Center ShanghaiShanghai, China.
Huajun ZhengShanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai Shanghai, China.
Weipeng ZhangDivision of Life Science, The Hong Kong University of Science and Technology Hong Kong, China.
Zhen ShenInstitute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
Miao ZhaoInstitute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
Yuancheng ChenInstitute of Antibiotics, Huashan Hospital, Fudan UniversityShanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning CommissionShanghai, China.
Li SunInstitute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
Jun ShiRoche Innovation Center Shanghai Shanghai, China.
Jing ZhangInstitute of Antibiotics, Huashan Hospital, Fudan UniversityShanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning CommissionShanghai, China.
Fudan University · CNChinese National Human Genome Center · CNHong Kong University of Science and Technology · HKRoche (China) · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cefoperazone/sulbactam has been shown to be efficacious for the treatment of infections caused by Acinetobacter baumannii; however, the mechanism underlying resistance to this synergistic combination is not well understood. In the present study, two A. baumannii isolates, AB1845 and AB2092, were isolated from a patient with hospital-acquired pneumonia before and after 20 days of cefoperazone/sulbactam therapy (2:1, 3 g every 8 h with a 1-h infusion). The minimum inhibitory concentration (MIC) of cefoperazone/sulbactam for AB1845 and AB2092 was 16/8 and 128/64 mg/L, respectively. Blood samples were collected on day 4 of the treatment to determine the concentration of cefoperazone and sulbactam. The pharmacokinetic/pharmacodynamic (PK/PD) indices (%T>MIC) were calculated to evaluate the dosage regimen and resistance development. The results showed that %T>MIC of cefoperazone and sulbactam was 100% and 34.5% for AB1845, and 0% and 0% for AB2092, respectively. Although there was no available PK/PD target for sulbactam, it was proposed that sulbactam should be administered at higher doses or for prolonged infusion times to achieve better efficacy. To investigate the mechanism of A. baumannii resistance to the cefoperazone/sulbactam combination in vivo, whole-genome sequencing of these two isolates was further performed. The sequencing results showed that 97.6% of the genome sequences were identical and 33 non-synonymous mutations were detected between AB1845 and AB2092. The only difference of these two isolates was showed in sequencing coverage comparison. There was a 6-kb amplified DNA fragment which was three times higher in AB2092, compared with AB1845. The amplified DNA fragment containing the bla OXA-23 gene on transposon Tn2009. Further quantitative real-time PCR results demonstrated that gene expression at the mRNA level of bla OXA-23 was >5 times higher in AB2092 than in AB1845. These results suggested that the bla OXA-23 gene had higher expression level in AB2092 via gene amplification and following transcription. Because gene amplification plays a critical role in antibiotic resistance in many bacteria, it is very likely that the bla OXA-23 amplification results in the development of cefoperazone/sulbactam resistance in vivo.

Indexed as

Acinetobacter baumanniicefoperazone/sulbactamPK/PD indicesresistance developmentwhole-genome sequencing

Identifiers

PMID27594850
PMCPMC4990596
OpenAlexW2517350591

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.