scholarly journals In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types

2021 ◽  
Vol 12 ◽  
Author(s):  
Jocelyn Qi-Min Teo ◽  
Nazira Fauzi ◽  
Jayden Jun-Yuan Ho ◽  
Si Hui Tan ◽  
Shannon Jing-Yi Lee ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bactericidal Activity ◽  
Carbapenem Resistance ◽  
Polymyxin B ◽  
Apparent Difference ◽  
Initial Inoculum ◽  
Carbapenem Resistant ◽  
Limited Effectiveness ◽  
Sequence Types

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is becoming increasingly problematic due to the limited effectiveness of new antimicrobials or other factors such as treatment cost. Thus, combination therapy remains a suitable treatment option. We aimed to evaluate the in vitro bactericidal activity of various antibiotic combinations against CRKP with different carbapenemase genotypes and sequence types (STs). Thirty-seven CRKP with various STs and carbapenemases were exposed to 11 antibiotic combinations (polymyxin B or tigecycline in combination with β-lactams including aztreonam, cefepime, piperacillin/tazobactam, doripenem, meropenem, and polymyxin B with tigecycline) in static time-kill studies (TKS) using clinically achievable concentrations. Out of the 407 isolate-combination pairs, only 146 (35.8%) were bactericidal (≥3 log10CFU/mL decrease from initial inoculum). Polymyxin B in combination with doripenem, meropenem, or cefepime was the most active, each demonstrating bactericidal activity in 27, 24, and 24 out of 37 isolates, respectively. Tigecycline in combination with β-lactams was rarely bactericidal. Aside from the lower frequency of bactericidal activity in the dual-carbapenemase producers, there was no apparent difference in combination activity among the strains with other carbapenemase types. In addition, bactericidal combinations were varied even in strains with similar STs, carbapenemases, and other genomic characteristics. Our findings demonstrate that the bactericidal activity of antibiotic combinations is highly strain-specific likely owing to the complex interplay of carbapenem-resistance mechanisms, i.e., carbapenemase genotype alone cannot predict in vitro bactericidal activity. The availability of WGS information can help rationalize the activity of certain combinations. Further studies should explore the use of genomic markers with phenotypic information to predict combination activity.

scholarly journals In Vitro Double and Triple Bactericidal Activities of Doripenem, Polymyxin B, and Rifampin against Multidrug-Resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli

2010 ◽  
Vol 54 (6) ◽  
pp. 2732-2734 ◽  
Author(s):  
Carl Urban ◽  
Noriel Mariano ◽  
James J. Rahal
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Carbapenem Resistant ◽  
Bactericidal Activities

ABSTRACT In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin were assessed against 20 carbapenem-resistant clinical isolates with different mechanisms of carbapenem resistance. Bactericidal activity was achieved in 90% of all bacteria assayed using combinations of polymyxin B, doripenem, and rifampin against five each of the carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli isolates studied. Combinations with these antibacterials may provide a strategy for treatment of patients infected with such organisms.

scholarly journals Enterobacteriaceae isolates carrying the New Delhi metallo-β-lactamase gene in Yemen

2014 ◽  
Vol 63 (10) ◽  
pp. 1316-1323 ◽  
Author(s):  
Alima Gharout-Sait ◽  
Samer-Ahmed Alsharapy ◽  
Lucien Brasme ◽  
Abdelaziz Touati ◽  
Rachida Kermas ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Susceptibility Testing ◽  
Enterobacter Cloacae ◽  
New Delhi ◽  
Carbapenem Resistant ◽  
Genes Encoding ◽  
Phenotypic Tests ◽  
Lactamase Gene ◽  
Sequence Types

Ten carbapenem-resistant Enterobacteriaceae (eight Klebsiella pneumoniae isolates and two Enterobacter cloacae) isolates from Yemen were investigated using in vitro antimicrobial susceptibility testing, phenotypic carbapenemase detection, multilocus sequence typing (MLST) and replicon typing. Carbapenemase, extended-spectrum β-lactamase (ESBL) and plasmid-mediated quinolone resistance determinant genes were identified using PCR and sequencing. All of the 10 carbapenem-resistant Enterobacteriaceae were resistant to β-lactams, tobramycin, ciprofloxacin and cotrimoxazole. Imipenem, doripenem and meropenem MICs ranged from 2 to >32 mg l−1 and ertapenem MICs ranged from 6 to >32 mg l−1. All of the K. pneumoniae isolates showed ESBL activity in phenotypic tests. Genes encoding bla NDM were detected in all strains. All K. pneumoniae strains produced CTX-M-15 ESBL and SHV β-lactamases. TEM-1 β-lactamase was detected in seven isolates. Nine isolates were qnr positive including QnrB1, QnrA1 and QnrS1, and six isolates produced AAC-6′-Ib-cr. MLST identified five different sequence types (STs): ST1399, ST147, ST29, ST405 and ST340. Replicon typing showed the presence of IncFII1K plasmids in four transformants. To the best of our knowledge, this is the first report of NDM-1-producing Enterobacteriaceae isolates in Yemen.

scholarly journals 1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S412-S413
Author(s):  
Michael R Jacobs ◽  
Caryn E Good ◽  
Ayman M Abdelhamed ◽  
Daniel D Rhoads ◽  
Kristine M Hujer ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Next Generation ◽  
Aminoglycoside Resistance ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Research Grant

Abstract Background Plazomicin is a next-generation aminoglycoside with in vitro activity against multidrug-resistant Gram-negative species, including carbapenem-resistant isolates. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, prospective multicenter consortium of 20 hospitals from nine US healthcare systems to track carbapenem-resistant Enterobacteriaceae. Methods Minimum inhibitory concentrations (MICs) of plazomicin were determined by broth microdilution according to current CLSI guidelines against a collection of 697 carbapenem-resistant Klebsiella pneumoniae with defined carbapenem resistance mechanisms, including KPC and OXA carbapenemases. Isolates were submitted by participating CRACKLE centers. Results Carbapenemases present in study isolates included KPC-2 (n = 323), KPC-3 (n = 364), KPC-4 (n = 2), OXA-48 like (n = 7), and NDM (n = 1). Plazomicin MICs ranged from ≤0.12 to >32 mg/L, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively (figure). MICs of 689 (98.8%) isolates were ≤4 mg/L, while MICs of the remaining eight isolates were >32 mg/L. Plazomicin MICs were related to specific carbapenemases present in isolates: of eight isolates with MICs >32 mg/L, seven contained OXA-48 like and one contained KPC-3, suggesting that these isolates possess an aminoglycoside-resistance mechanism on the same plasmid as their carbapenemase gene, such as a 16S ribosomal RNA methyltransferase, against which plazomicin is not active. Conclusion Plazomicin has good in vitro potency against a collection of carbapenemase-producing K. pneumoniae, with MIC90 value of 1 mg/L and MICs of ≤4 mg/L for 98.9% of isolates. Disclosures M. R. Jacobs, Achaogen: Investigator, Research grant. Shionogi: Investigator, Research grant. L. Connolly, Achaogen, Inc.: Consultant, Consulting fee. K. M. Krause, Achaogen: Employee, Salary. S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant. D. Van Duin, achaogen: Scientific Advisor, Consulting fee. shionogi: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee.

scholarly journals Comparative Effectiveness of Aminoglycosides, Polymyxin B, and Tigecycline for Clearance of Carbapenem-Resistant Klebsiella pneumoniae from Urine

2011 ◽  
Vol 55 (12) ◽  
pp. 5893-5899 ◽  
Author(s):  
Michael J. Satlin ◽  
Christine J. Kubin ◽  
Jill S. Blumenthal ◽  
Andrew B. Cohen ◽  
E. Yoko Furuya ◽  
...  
Keyword(s):  
New York ◽  
Klebsiella Pneumoniae ◽  
Urine Culture ◽  
Active Agent ◽  
Polymyxin B ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Tract Infections

ABSTRACTCarbapenem-resistantKlebsiella pneumoniae(CRKP) is an increasingly common cause of health care-associated urinary tract infections. Antimicrobials within vitroactivity against CRKP are typically limited to polymyxins, tigecycline, and often, aminoglycosides. We conducted a retrospective cohort study of cases of CRKP bacteriuria at New York-Presbyterian Hospital from January 2005 through June 2010 to compare microbiologic clearance rates based on the use of polymyxin B, tigecycline, or an aminoglycoside. We constructed three active antimicrobial cohorts based on the active agent used and an untreated cohort of cases that did not receive antimicrobial therapy with Gram-negative activity. Microbiologic clearance was defined as having a follow-up urine culture that did not yield CRKP. Cases without an appropriate follow-up culture or that received multiple active agents or less than 3 days of the active agent were excluded. Eighty-seven cases were included in the active antimicrobial cohorts, and 69 were included in the untreated cohort. The microbiologic clearance rate was 88% in the aminoglycoside cohort (n= 41), compared to 64% in the polymyxin B (P= 0.02;n= 25), 43% in the tigecycline (P< 0.001;n= 21), and 36% in the untreated (P< 0.001;n= 69) cohorts. Using multivariate analysis, the odds of clearance were lower for the polymyxin B (odds ratio [OR], 0.10;P= 0.003), tigecycline (OR, 0.08;P= 0.001), and untreated (OR, 0.14;P= 0.003) cohorts than for the aminoglycoside cohort. Treatment with an aminoglycoside, when activein vitro, was associated with a significantly higher rate of microbiologic clearance of CRKP bacteriuria than treatment with either polymyxin B or tigecycline.

scholarly journals OmpK26, a Novel Porin Associated with Carbapenem Resistance in Klebsiella pneumoniae

2011 ◽  
Vol 55 (10) ◽  
pp. 4742-4747 ◽  
Author(s):  
Laura García-Sureda ◽  
Antonio Doménech-Sánchez ◽  
Mariette Barbier ◽  
Carlos Juan ◽  
Joan Gascó ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Outer Membrane Proteins ◽  
Systemic Infection ◽  
Carbapenem Resistance ◽  
Resistant Isolate ◽  
Identical Result ◽  
Sequencing Analysis ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACTClinical isolates ofKlebsiella pneumoniaeresistant to carbapenems are being isolated with increasing frequency. Loss of the expression of the major nonspecific porins OmpK35/36 is a frequent feature in these isolates. In this study, we looked for porins that could compensate for the loss of the major porins in carbapenem-resistant organisms. Comparison of the outer membrane proteins from twoK. pneumoniaeclinical isogenic isolates that are susceptible (KpCS-1) and resistant (KpCR-1) to carbapenems revealed the absence of OmpK35/36 and the presence of a new 26-kDa protein in the resistant isolate. An identical result was obtained when another pair of isogenic isolates that are homoresistant (Kpn-3) and heteroresistant (Kpn-17) to carbapenems were compared. Mass spectrometry and DNA sequencing analysis demonstrated that this new protein, designated OmpK26, is a small monomeric oligogalacturonate-specific porin that belongs to the KdgM family of porins. Insertion-duplication mutagenesis of the OmpK26 coding gene,yjhA, in the carbapenem-resistant, porin-deficient isolate KpCR-1 caused the expression of OmpK36 and the reversion to the carbapenem-susceptible phenotype, suggesting that OmpK26 is indispensable for KpCR-1 to lose OmpK36 and become resistant to these antibiotics. Moreover, loss of the major porin and expression of OmpK26 reducedin vitrofitness and attenuated virulence in a murine model of acute systemic infection. Altogether, these results indicate that expression of the oligogalacturonate-specific porin OmpK26 compensates for the absence of OmpK35/36 and allows carbapenem resistance inK. pneumoniaebut cannot restore the fitness of the microorganism.

scholarly journals Carbapenem-Resistant Klebsiella pneumoniae Strains Exhibit Diversity in Aminoglycoside-Modifying Enzymes, Which Exert Differing Effects on Plazomicin and Other Agents

2014 ◽  
Vol 58 (8) ◽  
pp. 4443-4451 ◽  
Author(s):  
Reem Almaghrabi ◽  
Cornelius J. Clancy ◽  
Yohei Doi ◽  
Binghua Hao ◽  
Liang Chen ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Bactericidal Activity ◽  
Sequence Type ◽  
Content Type ◽  
Molecular Assays ◽  
Carbapenem Resistant ◽  
Research Priority ◽  
Gentamicin Resistance

ABSTRACTWe measuredin vitroactivity of plazomicin, a next-generation aminoglycoside, and other aminoglycosides against 50 carbapenem-resistantKlebsiella pneumoniaestrains from two centers and correlated the results with the presence of various aminoglycoside-modifying enzymes (AMEs). Ninety-four percent of strains were sequence type 258 (ST258) clones, which exhibited 5ompK36genotypes; 80% and 10% of strains producedKlebsiella pneumoniaecarbapenemase 2 (KPC-2) and KPC-3, respectively. Ninety-eight percent of strains possessed AMEs, including AAC(6′)-Ib (98%), APH(3′)-Ia (56%), AAC(3)-IV (38%), and ANT(2″)-Ia (2%). Gentamicin, tobramycin, and amikacin nonsusceptibility rates were 40, 98, and 16%, respectively. Plazomicin MICs ranged from 0.25 to 1 μg/ml. Tobramycin and plazomicin MICs correlated with gentamicin MICs (r= 0.75 and 0.57, respectively). Plazomicin exerted bactericidal activity against 17% (1× MIC) and 94% (4× MIC) of strains. All strains with AAC(6′)-Ib were tobramycin-resistant; 16% were nonsusceptible to amikacin. AAC(6′)-Ib combined with another AME was associated with higher gentamicin, tobramycin, and plazomicin MICs than AAC(6′)-Ib alone (P= 0.01, 0.0008, and 0.046, respectively). The presence of AAC(3)-IV in a strain was also associated with higher gentamicin, tobramycin, and plazomicin MICs (P= 0.0006,P< 0.0001, andP= 0.01, respectively). The combination of AAC(6′)-Ib and another AME, the presence of AAC(3)-IV, and the presence of APH(3′)-Ia were each associated with gentamicin resistance (P= 0.0002, 0.003, and 0.01, respectively). In conclusion, carbapenem-resistantK. pneumoniaestrains (including ST258 clones) exhibit highly diverse antimicrobial resistance genotypes and phenotypes. Plazomicin may offer a treatment option against strains resistant to other aminoglycosides. The development of molecular assays that predict antimicrobial responses among carbapenem-resistantK. pneumoniaestrains should be a research priority.

scholarly journals Comparative analysis of Clinial Carbapenem- Resistant (CR), Hypermucoviscous (HM) and CR-HM Klebsiella pneumoniae isolates in China

2020 ◽  
Author(s):  
Jun-Ying Zhu ◽  
Guang-Yu Wang ◽  
Qing Wei ◽  
Zhen Shen ◽  
Qiong Li ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Virulence Genes ◽  
Carbapenem Resistance ◽  
Resistance Rate ◽  
Molecular Characteristics ◽  
Carbapenem Resistant ◽  
Recent Emergence ◽  
String Test

Abstract Background: Although carbapenem-resistant Klebsiella pneumoniae (CRKP) and hypermucoviscous K. pneumoniae (HMKP) were largely non-overlapping, the recent emergence of CR-HMKP has raised great alarm in the world. We compared the molecular characteristics of CRKP, HMKP and CR-HMKP isolates.Results: 220 cases of K. pneumoniae isolates was collected and identified between Jan 2015 and Dec 2016 from Renji Hospital. Carbapenem resistance test and string test were performed to screen CRKP, HMKP and CR-HMKP isolates. All the CRKP, HMKP and CR-HMKP isolates were investigated for capsular genotyping, virulence genes and resistance genes by PCR and DNA sequencing. Multilocus sequence typing (MLST) was used to characterize isolates sequence types (STs). Serum killing assay and mouse lethality assay were respectively performed to confirm the virulence of the isolates in vitro and in vivo. Of 220 K. pneumoniae，71 HMKP, 84 CRKP and 8 CR-HMKP were identified. Resistance rate to carbapenems was significantly higher in CRKP than HMKP and CR-HMKP. For MLST and serotyping, ST23 (26.8%)，K1 (33.8%) and K2 (23.9%) serotypes were the most common in HMKP isolates while ST11 (84.5%, 100%) and K-nontypable (91.6%, 100%) were the predominant types in CRKP and CR-HMKP isolates. The existence of virulence genes rmpA, magA and iutA was significantly higher in HMKP while the prevalence of resistance gene blaKPC-2 was higher in CRKP and CR-HMKP. Virulence test in vivo and in vitro both showed the lower virulence of CRKP and CR-HMKP compared to HMKP.Conclusions: In spite of low virulence, the emergence of CR-HMKP indicates a confluence of hypermucoviscous phenotype and carbapenem resistance. Furthermore, the similar molecular characteristics between CRKP and CR-HMKP suggested that CR-HMKP might evolve from CRKP.

Ceftazidime/avibactam and eravacycline susceptibility of carbapenem-resistant Klebsiella pneumoniae in two Greek tertiary teaching hospitals

2021 ◽  
Author(s):  
Maria Chatzidimitriou ◽  
Panagiota Chatzivasileiou ◽  
Georgios Sakellariou ◽  
MariaAnna Kyriazidi ◽  
Asimoula Kavvada ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Antimicrobial Agents ◽  
Carbapenem Resistance ◽  
Teaching Hospitals ◽  
Diffusion Method ◽  
Strain Identification ◽  
Disk Diffusion Method ◽  
Carbapenem Resistant ◽  
Tertiary Teaching

AbstractThe present study evaluated the carbapenem resistance mechanisms of Klebsiella pneumoniae strains isolated in two Greek tertiary teaching hospitals and their susceptibility to currently used and novel antimicrobial agents.Forty-seven carbapenem resistant K. pneumoniae strains were collected in G. Papanikolaou and Ippokrateio hospital of Thessaloniki between 2016 and 2018. Strain identification and antimicrobial susceptibility was conducted by Vitek 2 system (Biomérieux France). Susceptibility against new antimicrobial agents was examined by disk diffusion method. Polymerase chain reaction (PCR) was used to detect blaKPC, blaVIM, blaNDM and blaOXA-48 genes.The meropenem–EDTA and meropenem–boronic acid synergy test performed on the 24 K. pneumoniae strains demonstrated that 8 (33.3%) yielded positive for metallo-beta-lactamases (MBL) and 16 (66.6%) for K. pneumonia carbapenemases (KPC) production. Colistin demonstrated the highest in vitro activity (87.7%) among the 47 K. pneumoniae strains followed by gentamicin (76.5%) and tigecycline (51%). Among new antibiotics ceftazidime/avibactam showed the highest sensitivity (76.6%) in all strains followed by eravacycline (66.6%). The blaKPC gene was present in 30 strains (63.8%), the blaNDM in 11 (23.4%) and the blaVIM in 6 (12.8%). The blaOXA-48 gene was not detected.Well established antimicrobial agents such as colistin, gentamicin and tigecycline and novel antibiotics like ceftazidime/avibactam and eravacycline can be reliable options for the treatment of invasive infections caused by carbapenem-resistant K. pneumoniae.

scholarly journals Risk Factors for Treatment Failure of Polymyxin B Monotherapy for Carbapenem-Resistant Klebsiella pneumoniae Infections

2013 ◽  
Vol 57 (11) ◽  
pp. 5394-5397 ◽  
Author(s):  
Yanina Dubrovskaya ◽  
Ting-Yi Chen ◽  
Marco R. Scipione ◽  
Diana Esaian ◽  
Michael S. Phillips ◽  
...  
Keyword(s):  
Risk Factors ◽  
Septic Shock ◽  
Klebsiella Pneumoniae ◽  
Renal Insufficiency ◽  
Treatment Failure ◽  
Clinical Cure ◽  
Polymyxin B ◽  
Antimicrobial Treatment ◽  
Carbapenem Resistant

ABSTRACTPolymyxins are reserved for salvage therapy of infections caused by carbapenem-resistantKlebsiella pneumoniae(CRKP). Though synergy has been demonstrated for the combination of polymyxins with carbapenems or tigecycline,in vitrosynergy tests are nonstandardized, and the clinical effect of synergy remains unclear. This study describes outcomes for patients with CRKP infections who were treated with polymyxin B monotherapy. We retrospectively reviewed the medical records of patients with CRKP infections who received polymyxin B monotherapy from 2007 to 2011. Clinical, microbiology, and antimicrobial treatment data were collected. Risk factors for treatment failure were identified by logistic regression. Forty patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved clinical cure as defined by clinician-documented improvement in signs and symptoms of infections, and 17/32 (53%) patients with follow-up culture data achieved microbiological cure. End-of-treatment mortality was 10%, and 30-day mortality was 28%. In a multivariate analysis, baseline renal insufficiency was associated with a 6.0-fold increase in clinical failure after adjusting for septic shock (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 1.22 to 29.59). Breakthrough infections with organisms intrinsically resistant to polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%) patients developed a new CRKP infection a median of 23 days after initial polymyxin B treatment, and 3 of these 18 infections were polymyxin resistant. The clinical cure rate achieved in this retrospective study was 73% of patients with CRKP infections treated with polymyxin B monotherapy. Baseline renal insufficiency was a risk factor for treatment failure after adjusting for septic shock. Breakthrough infections with organisms intrinsically resistant to polymyxin B and development of resistance to polymyxin B in subsequent CRKP isolates are of concern.

scholarly journals In Vitro Synergism of Azithromycin Combination with Antibiotics against OXA-48-Producing Klebsiella pneumoniae Clinical Isolates

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1551
Author(s):  
Uthaibhorn Singkham-in ◽  
Netchanok Muhummudaree ◽  
Tanittha Chatsuwan
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Outer Membrane Proteins ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
In Vitro Activity ◽  
Bacterial Regrowth ◽  
Antibiotic Development ◽  
Carbapenem Resistant

Carbapenem-resistant Klebsiella pneumoniae has globally emerged as an urgent threat leading to the limitation for treatment. K. pneumoniae carrying blaOXA-48, which plays a broad magnitude of carbapenem susceptibility, is widely concerned. This study aimed to characterize related carbapenem resistance mechanisms and forage for new antibiotic combinations to combat blaOXA-48-carrying K. pneumoniae. Among nine isolates, there were two major clones and a singleton identified by ERIC-PCR. Most isolates were resistant to ertapenem (MIC range: 2–>256 mg/L), but two isolates were susceptible to imipenem and meropenem (MIC range: 0.5–1 mg/L). All blaOXA-48-carrying plasmids conferred carbapenem resistance in Escherichia coli transformants. Two ertapenem-susceptible isolates carried both outer membrane proteins (OMPs), OmpK35 and OmpK36. Lack of at least an OMP was present in imipenem-resistant isolates. We evaluated the in vitro activity of an overlooked antibiotic, azithromycin, in combination with other antibiotics. Remarkably, azithromycin exhibited synergism with colistin and fosfomycin by 88.89% and 77.78%, respectively. Bacterial regrowth occurred after exposure to colistin or azithromycin alone. Interestingly, most isolates were killed, reaching synergism by this combination. In conclusion, the combination of azithromycin and colistin may be an alternative strategy in dealing with blaOXA-48-carrying K. pneumoniae infection during a recent shortage of newly effective antibiotic development.

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