Skip to main content

High prevalence of carbapenem resistance and clonal expansion of blaNDM gene in Klebsiella pneumoniae isolates in an Iranian referral pediatric hospital



The increasing global concern regarding antibiotic resistance necessitates in-depth studies to comprehend the phenotypic and genotypic characteristics of resistant bacterial strains. This study aimed to investigate the prevalence, antibiotic resistance profiles, and molecular characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in an Iranian referral pediatrics hospital. Methods: In this study, we examined CRKP isolates collected from hospitalized pediatric patients across various wards. The isolates underwent antimicrobial susceptibility testing, the polymerase chain reaction (PCR) analysis for carbapenemase genes (blaNDM, blaVIM and blaIMP), and genetic relatedness assessment using pulsed-field gel electrophoresis (PFGE).


Among 166 K. pneumoniae isolates, 54 (32.5%) exhibited resistance to carbapenems. Notably, all these resistant isolates were resistant to imipenem, with 35 (65%) displaying resistance to both imipenem and meropenem. Of the 54 CRKP isolates, 24 (44%) were metallo-β-lactamases (MBL)-producing. The prevalence of the blaNDM gene among CKCP and MBL-producing isolates was 20% (n = 11) and 44% (n = 24), respectively. The blaVIM and blaIMP genes were not detected in any of the isolates. Twenty-six CRKP isolates (48%) were recovered from ICUs. PFGE analysis of CRKP isolates revealed 20 clusters, with cluster S being the most prevalent, comprising 24% of the total (n = 13).


Our study reveals a concerning prevalence of carbapenem resistance in K. pneumoniae isolates. Specifically, the detection of the blaNDM gene in 20% of CRKP isolates, with a significant proportion (82%) observed in isolated CRKP from the ICUs and emergency departments, underscores the potential clonal expansion of these resistant strains within these critical hospital wards.


Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant challenge in healthcare, presenting a substantial threat due to its resistance to essential antibiotics [1,2,3,4]. The increasing prevalence of CRKP is particularly noteworthy within healthcare settings, where infections caused by these strains are linked to limited treatment options and heightened patient morbidity and mortality. The implications extend beyond individual patient outcomes to encompass broader concerns related to infection control, antimicrobial stewardship, and public health [5].

The predominant mechanism of carbapenem resistance in carbapenem-resistant Enterobacteriaceae (CRE) involves the production of carbapenemase enzymes. Notable enzymes include those belonging to class A, such as Klebsiella pneumoniae carbapenemases (KPC), class B metallo-β-lactamases (MBL) like New Delhi MBL (NDM), verona integron-encoded MBL (VIM), and Imipenemase (IMP), and class D enzymes such as oxacillinases (OXA-48) [4]. In recent years in Iran, there has been an emergence of OXA-48 and NDM-1 producing K. pneumoniae strains associated with distinct clones, particularly ST11, ST893, and ST147 [6, 7]. The rising prevalence of MBL-producing gram-negative isolates, particularly strains of K. pneumoniae carrying the blaNDM gene, in our hospitals is becoming a significant cause for concern [8]. This trend signifies a growing challenge in the management of bacterial infections, as MBLs are enzymes capable of hydrolyzing a broad range of beta-lactam antibiotics, including carbapenems. The spread of these resistant strains could potentially lead to limited treatment options, increased mortality rates, prolonged hospitalization, and higher healthcare costs. Addressing this concern requires a comprehensive approach, including enhanced surveillance, infection control measures, antibiotic stewardship, and continued research to understand the epidemiology and mechanisms of resistance. In response to this concern, we have decided to initiate a genotyping study employing Pulsed-Field Gel Electrophoresis (PFGE) specifically for CRKP isolates within our hospital. This initiative is crucial for enhancing our comprehension of the local dynamics of CRKP strains, enabling us to implement targeted measures for infection control and contribute to a more effective management strategy. The main objective of this study was to conduct genotyping on CRKP isolates collected over the course of one year using the PFGE method at Children’s Medical Center (CMC), Tehran, Iran.


Study design

The study was conducted at the CMC, known as Iranian leading hospital for pediatric healthcare, education, and research between April 2021 and March 2022. With an extensive capacity of over 300 beds, CMC hosts more than 20 specialty and subspecialty wards. The Intensive Care Unit (ICU) facilities at CMC Hospital include the Pediatric Intensive Care Unit (PICU), the Neonatal Intensive Care Unit (NICU) for newborn infants, NICU OH for neonates following open heart and cardiac surgery, cardiac intensive care unit (CICU), and the infant ICU (IICU). The emergency ward, equipped with 40 beds, serves as a major referral center in the country, complemented by a 9-bed ICU.

This study was approved by the Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.CHMC.REC.1398.109).

Bacterial identification and antibiotic susceptibility testing

Identification of K. pneumoniae was performed by using conventional biochemical methods. Preliminary identification of bacteria was done based on colony characteristics of grown isolates on media. Various biochemical tests were employed to identify K. pneumoniae isolates, including triple sugar iron agar, indole, motility, hydrogen sulfide production, citrate utilization, urease production, and lysine decarboxylase tests. All isolates were stored at -80 °C in tryptic soy broth (Merk, Germany) and 15% glycerol for further molecular studies.

The antimicrobial susceptibility of K. pneumoniae isolates was assessed using the Kirby-Bauer disk diffusion method on Mueller Hinton agar (Merck, Germany). Antimicrobial agents that were tested are as follows: ciprofloxacin (5 µg), cefepime (30 µg), cefotaxime (30 µg), amikacin (30 µg), gentamcin (10 µg), piperacillin/tazobactam (110/10 µg), colistin (50 µg), trimethoprim-sulfamethoxazole (1.25/23.75 µg), and nitrofurantoin (300 µg). The results were interpreted according to the guidelines recommended by the Clinical and Laboratory Standards Institute (CLSI) [9]. Minimum inhibitory concentrations (MICs) for meropenem and imipenem were determined using E-test, and the interpretations were based on breakpoints provided by CLSI [9]. The antibiotics were obtained from MAST, UK. E. coli ATCC 25,922 and Pseudomonas aeruginosa ATCC 27,853 were used as quality control strains. CRKP clinical isolates were recognized by resistant to at least one of the carbapenem (imipenem, meropenem) based on CLSI guidelines.

We used the double disk synergy test (DDST) for the phenotypic identification of MBL-producing isolates [8].

Polymerase chain reaction (PCR) assays

The DNA of all CRKP strains was extracted using the DNA extraction kit (GeNet Bio Company, Daejeon, Korea) according to the manufacturer’s instruction. Following extraction, PCR analysis was conducted targeting the blaNDM, blaVIM and blaIMP genes using specific primers as previously described [8].


Genetic relationships of the CRKP isolates were assessed using PFGE. The genomic DNA was embedded in 1% agarose blocks and then subjected to enzymatic digestion with 50 U Fast XbaI restriction enzyme for 30 min. Subsequently, the DNA fragments were separated using the CHEF-DR II system (Bio-Rad Laboratories), employing 1% agarose (SeaKem Gold®) gel at a voltage of 6 V/cm. The electrophoresis parameters included an initial pulse duration of 2.2 s, a final pulse duration of 63.8 s, and a running temperature of 14 °C for a total duration of 22 h. The standard strain Salmonella enterica serotype Braenderup H9812 was employed as a reference [10].

The electrophoretic patterns obtained were analyzed through visual inspection to detect the position and number of bands. The DNA pattern was analyzed using Gelcompar II version 6.5 software (Applied Maths, Belgium). A similarity coefficient was determined using Dice coefficients, followed by cluster analysis using the unweighted pair group method with arithmetic averages (UPGMA). Isolates displaying a similarity cut-off of ≥ 80% in their banding patterns were classified as belonging to the same clonal lineage.

Statistical analysis

Statistical analyses were carried out using IBM SPSS Statistics (version 23.0, IBM Corp. Armonk, NY, USA). Descriptive statistics such as mean, percentage and frequency were used to indicate categorical data. The variables underwent evaluation through the chi-square test. In accordance with this study, statistical significance was defined as a p-value of ≤ 0.05.


A total of 166 isolates of K. pneumoniae were collected from patients, with 54 (32.5%) identified as CRKP. Among the 54 CRKP isolates, 65% (n = 35) were obtained from male. The median age of the patients was 2.6 months (interquartile range: 1 month- 4.2 years). The mean duration of hospital stay was 4.4 ± 3.5 days.

The samples yielding the highest number of isolates were urine, with twenty cases (37%), followed by blood, which produced fifteen isolates (28%). Next in frequency were isolates from bronchoalveolar lavage (BAL), accounting for five cases (9%), and wounds, contributing three cases (6%). Eye discharge yielded two isolates (4%), while throat, cerebrospinal fluid (CSF), sputum, and dialysis fluid, each resulted in one isolate (2%). An additional five isolates (10%) were obtained from other sources. The PICU had the highest number of CRKP isolates at 19% (n = 10), followed by emergency with 17% (n = 9) and NICU with 13% (n = 7). Surgery 1 and NICU OH comprised 9% (n = 5) and 7% (n = 4) of the isolates, respectively, while nephrology, neonatal, and IICU each contributed 6% (n = 3). CICU, cardiopulmonary, gastroenterology, and urology each accounted for 4% (n = 2), while surgery 2 and neurology had the lowest representation at 2% (n = 1) each.

In this study, 32.5% of K. pneumoniae isolates demonstrated carbapenem resistance. The antibiotic resistance pattern observed in the isolates of CKCP was as follows: imipenem (54 out of 54, 100%), cefotaxime (49 out of 54, 91%), cefepime (45 out of 54, 83%), piperacillin-tazobactam (43 out of 54, 80%), nitrofurantoin (14 out of 18, 74%), amikacin (39 out of 54, 72%), trimethoprim-sulfamethoxazole (35 out of 54, 65%), meropenem (35 out of 54, 65%), ciprofloxacin (11 out of 19, 58%), gentamicin (29 out of 54, 54%), and colistin (2 out of 15, 13%). DDST results showed that 24 CKCP isolates (44%) were MBL-producing ones. The prevalence of the blaNDM gene among the CKCP and MBL-producing isolates was 20% (n = 11) and 44% (n = 24), respectively. The blaVIM and blaIMP genes were not detected in any of the isolates.

Figure 1 illustrates the antimicrobial resistance of CKCP isolates across various wards. In the PICU and NICU, antibiotic resistance rates were notably high.

Fig. 1
figure 1

Antimicrobial resistance patterns of the CRKP isolates obtained from patients across various hospital wards

PFGE analysis of the CRKP isolates identified 20 clusters, with cluster S being the most prevalent, comprising 24% of the total (n = 13) (Fig. 2). Following, clusters A, C, and N each accounted for 9% of the isolates, with five samples in each cluster. Cluster B and J represented 6% of the isolates, with three samples each. The distribution of different clusters across various hospital wards illustrates varied patterns of occurrence (Table 1). Cluster A was predominantly found in the NICU, representing 60% of occurrences. Cluster B was primarily observed in the PICU, constituting 67% of occurrences. Cluster C was distributed across multiple wards, with 40% of occurrences in PICU and minor presence in IICU, NICU OH, and emergency wards. Cluster D was solely identified in the neonatal ward. Cluster E exhibited an equal distribution across urology, cardiopulmonary, and surgery 1 wards. Cluster J and cluster K were solely observed in the emergency and PICU, respectively. Cluster L was solely present in NICU. Cluster M was distributed across nephrology, surgery 1, emergency, and NICU wards. Cluster S was predominantly found in the emergency ward (23%) and also observed in the CICU and PICU (each 15%). It appears in other wards as well, including urology, surgery 2, nephrology, and cardiopulmonary wards.

Fig. 2
figure 2

Dendrogram of PFGE typing of 53 CRKP isolates, cluster classification based on ≥ 80% similarity genotypes

Table 1 The distribution of CRKP isolates in CMC hospital

Figure 3a illustrates the distribution of blaNDM -positive CRKP isolates. Cluster C exhibited the highest occurrence, with four samples identified as blaNDM -positive CRKP isolates. Clusters L accounted for two blaNDM -positive CRKP isolates. Additionally, Clusters A, B, E, and O each contributed one blaNDM-positive CRKP isolate. Furthermore, one blaNDM -positive CRKP isolate was classified as non-typable.

Fig. 3
figure 3

The distribution of CRKP isolates harboring the blaNDM gene; (a) by cluster, (b) by wards

The majority of blaNDM-positive CRKP isolates were observed in the PICU, constituting 36% of isolates. Additionally, the emergency ward accounted for 18% of occurrences, while NICU OH, IICU, NICU, Surgery 1, and cardiopulmonary wards each had 9% representation of blaNDM-positive CRKP isolates (Fig. 3b).


The emergence of CRKP presents a significant challenge to worldwide public health, posing a substantial obstacle to effective clinical infection management [4, 11,12,13]. This study sought to explore the drug resistance profile and epidemiological features of CRKP at the CMC, with the overarching goal of implementing effective measures to curb the spread of CRKP infections among pediatric patients. In this study, 32.5% of K. pneumoniae isolates demonstrated carbapenem resistance. According to the latest meta-analysis, the global prevalence of CRKP in patients with K. pneumoniae infections was 28.69% (95% CI: 26.53–30.86%) [14]. In a previous study conducted at CMC between January 2018 and April 2020, K. pneumoniae isolates showed resistance rates of 38% to imipenem and 20% to meropenem.

In our study, the prevalence of MBL-producing K. pneumoniae isolates was found to be 44%, aligning with previous findings [8]. Among CKCP and MBL-producing isolates, the prevalence of the blaNDM gene was 20% and 83%, respectively. Notably, the prevalence of the blaNDM gene surpassed previous reports, wherein only 42% of MBL-producing isolates tested positive for blaNDM [8].

The high prevalence of CRKP complicates the management of nosocomial infections, underscoring the urgency for a reassessment of current infection control protocols and antibiotic stewardship strategies. The predominant risk factors commonly associated with CRE infection include the utilization of indwelling medical devices, previous exposure to antibiotics, and admission to the ICUs [4]. The substantial number of CRKP isolates, particularly isolated from urine (37%) and blood (28%), suggests a potential association with the utilization of indwelling medical devices. Urinary catheters and central venous catheters, frequently utilized in healthcare settings to address diverse medical needs and ensure critical patient care, establish an optimal environment for bacterial colonization. Moreover, prior antibiotic exposure is identified as another key risk factor driving the emergence and spread of CRE infections [15]. All patients included in our study had a history of previous hospitalization and prior antibiotic use. Enhanced infection control measures, including stringent adherence to hand hygiene protocols, judicious use of indwelling medical devices, and implementation of antimicrobial stewardship programs to optimize antibiotic use, are essential for controlling the spread of CRE.

Twenty-six CRKP isolates (48%) were obtained from ICUs, aligning with findings from other studies that have consistently reported the highest incidence of CRKP infections among patients admitted to ICU wards [16, 17]. According to the latest meta-analysis, the prevalence of hospital-acquired CRKP infections is notably high in ICUs, with a pooled estimate of 62.31% [14]. ICUs, characterized by high patient acuity, prolonged hospital stays, and frequent invasive procedures, provide a conducive environment for the transmission of healthcare-associated pathogens like CRE [18]. Furthermore, the compromised immune status of ICU patients, coupled with the frequent use of broad-spectrum antibiotics and invasive medical interventions, further heightens their susceptibility to CRE infections.

All CRKP isolates in our study were multidrug-resistant and showed high resistance to piperacillin-tazobactam and cephalosporins. The prevalence of resistance to colistin, and ciprofloxacin was low, which may be because of limited use of these antibiotics in children. This suggests that ciprofloxacin or colistin, in conjunction with other antibiotics such as meropenem and imipenem, may be useful for the treatment of complex CRKP infections.

Multiple outbreaks of CRKP infections carrying blaNDM genes have been reported in Iran [7, 19,20,21,22]. Research conducted in Turkey, Egypt, and Greece, examining the PFGE patterns of clinical CRKP isolates, has provided significant evidence supporting the transmission and prevalence of resistance within hospital wards, particularly in ICU settings [23,24,25]. In the investigation conducted by Tao et al. in China, the PFGE analysis of the 86 CRKP strains demonstrated their segregation into 15 separate clusters, primarily found within neonatal medicine, neonatal ward and ICU [26]. In the study conducted by Celikbilek et al. in Turkey, PFGE analysis revealed that over half of the CRKP isolates were grouped into clusters. However, cross-transmission was not limited to a specific wards or time period [25].

The current study also demonstrated that cross-transmission was not restricted to a single ward. For instance, despite the 13 CRKP isolates being clustered within the largest PFGE type, they were identified across various wards, including the CICU, emergency, urology, surgery, nephrology, cardiopulmonary, PICU, IICU, and neonatal department. Four CRKP isolates observed in cluster C harbored the blaNDM gene and were isolated from different ICU wards and emergency department. A significant association was observed between cluster C and the presence of the blaNDM gene. The lack of adequate infection control measures in our hospital raise concerns regarding the potential spread of CRKP through patient transfers, particularly from the emergency department to other wards. The detection of the blaNDM gene in other clusters implies the dissemination of this resistance gene across different wards within the hospital, thereby indicating the possibility of transmission to all wards. This clonal expansion has the potential to be transmitted to patients via personnel, equipment, or contaminated surfaces [25]. Therefore, it is highly recommended to enforce rigorous infection control protocols, encompassing effective isolation measures, thorough cleaning and disinfection protocols, and strict compliance with hand hygiene practices, to control the dissemination of CRKP within the hospital setting. Effective communication and collaboration among healthcare teams are vital to ensure that patients with CRKP colonization or infection are appropriately managed during transfers, thus minimizing the risk of further dissemination [5, 27].

While the blaNDM gene is a significant contributor to carbapenem resistance, there are other mechanisms, such as the production of carbapenemases like KPC and OXA enzymes, as well as non-enzymatic mechanisms involving alterations in porins and efflux pumps, that can also confer resistance to carbapenems. Understanding the full spectrum of resistance mechanisms is essential for developing comprehensive strategies to combat carbapenem-resistant infections effectively.

The study faced a limitation in its capacity to differentiate between colonization and infection with CRKP. An in-depth analysis of the definition of nosocomial infections could have provided a stronger foundation for the study and improved the interpretation of its findings. Conclusion.

In conclusion, our study revealed a concerning prevalence of carbapenem resistance among K. pneumoniae isolates. Specifically, the detection of the blaNDM gene in 20% of CRKP isolates, with a significant proportion (82%) observed in isolated CRKP from the ICUs and emergency departments, underscores the potential clonal expansion of these resistant strains within these critical hospital wards.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.



Carbapenem-resistant Klebsiella pneumoniae


Carbapenem-resistant Enterobacteriaceae


Klebsiella pneumoniae carbapenemases




New Delhi MBL


Verona integron-encoded MBL






Pulsed-field gel electrophoresis


Carbapenem-resistant Klebsiella pneumoniae


Intensive care unit


Pediatric intensive care unit


Neonatal intensive care unit


Neonatal intensive care unit following open heart and cardiac surgery


Infant ICU


Cardiac intensive care unit


Children’s Medical Center


Clinical and Laboratory Standards Institute


Unweighted pair group method with arithmetic averages


Minimum inhibitory concentrations


Double disk synergy test


Bronchoalveolar lavage


Cerebrospinal fluid


  1. Martin RM, Bachman MA. Colonization, infection, and the accessory genome of Klebsiella pneumoniae. Front Cell Infect Microbiol. 2018;8:4.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Afsharipour M, Mahmoudi S, Raji H, Pourakbari B, Mamishi S. Three-year evaluation of the nosocomial infections in pediatrics: bacterial and fungal profile and antimicrobial resistance pattern. Ann Clin Microbiol Antimicrob. 2022;21(1):6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mamishi S, Mahmoudi S, Naserzadeh N, Hosseinpour Sadeghi R, Haghi Ashtiani MT, Bahador A, et al. Antibiotic resistance and genotyping of gram-negative bacteria causing hospital-acquired infection in patients referred to children’s Medical Center. Infect Drug Resist. 2019;12:3377–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kedišaletše M, Phumuzile D, Angela D, Andrew W, Mae NF. Epidemiology, risk factors, and clinical outcomes of carbapenem-resistant enterobacterales in Africa: a systematic review. J Glob Antimicrob Resist. 2023;35:297–306.

    Article  PubMed  Google Scholar 

  5. Mamishi S, Pourakbari B, Teymuri M, Babamahmoodi A, Mahmoudi S. Management of hospital infection control in Iran: a need for implementation of multidisciplinary approach. Osong Public Health Res Perspect. 2014;5(4):179–86.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Solgi H, Nematzadeh S, Giske CG, Badmasti F, Westerlund F, Lin Y-L, et al. Molecular epidemiology of OXA-48 and NDM-1 producing enterobacterales species at a University Hospital in Tehran, Iran, between 2015 and 2016. Front Microbiol. 2020;11:936.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Sanikhani R, Akbari M, Hosseinzadeh M, Siavash M, Badmasti F, Solgi H. Outbreak of colistin and carbapenem-resistant Klebsiella pneumoniae ST16 co-producing NDM-1 and OXA-48 isolates in an Iranian hospital. BMC Microbiol. 2024;24(1):59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mahmoudi S, Pourakbari B, Rostamyan M, Raji H, Sadeghi RH, Mamishi S. Antimicrobial resistance patterns of Gram-negative bacteria in an Iranian referral pediatric hospital: a present danger of New Delhi metallo-β-lactamase. Infect Disord Drug Targets. 2023.

  9. (CLSI) CaLSI. Performance Standards for Antimicrobial Susceptibility Testing. CLSI Approved Standard M100Ed31. 2021.

  10. Wang Z, Li M, Shen X, Wang L, Liu L, Hao Z, et al. Outbreak of Bla NDM-5-Harboring Klebsiella pneumoniae ST290 in a Tertiary Hospital in China. Microb Drug Resist. 2019;25(10):1443–8.

    Article  CAS  PubMed  Google Scholar 

  11. Chen J, Ma H, Huang X, Cui Y, Peng W, Zhu F, et al. Risk factors and mortality of carbapenem-resistant Klebsiella pneumoniae bloodstream infection in a tertiary-care hospital in China: an eight-year retrospective study. Antimicrob Resist Infect Control. 2022;11(1):161.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Abdelaziz NA. Phenotype-genotype correlations among carbapenem-resistant Enterobacterales recovered from four Egyptian hospitals with the report of SPM carbapenemase. Antimicrob Resist Infect Control. 2022;11(1):13.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Tilahun M, Kassa Y, Gedefie A, Ashagire M. Emerging carbapenem-resistant Enterobacteriaceae infection, its epidemiology and Novel Treatment options: a review. Infect Drug Resist. 2021;14:4363–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lin XC, Li CL, Zhang SY, Yang XF, Jiang M. The Global and Regional Prevalence of Hospital-Acquired Carbapenem-resistant Klebsiella pneumoniae infection: a systematic review and Meta-analysis. Open Forum Infect Dis. 2024;11(2):ofad649.

    Article  PubMed  Google Scholar 

  15. Chiotos K, Han JH, Tamma PD. Carbapenem-Resistant Enterobacteriaceae infections in Children. Curr Infect Dis Rep. 2016;18(1):2.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sotgiu G, Are B, Pesapane L, Palmieri A, Muresu N, Cossu A, et al. Nosocomial transmission of carbapenem-resistant Klebsiella pneumoniae in an Italian university hospital: a molecular epidemiological study. J Hosp Infect. 2018;99(4):413–8.

    Article  CAS  PubMed  Google Scholar 

  17. Hu Y, Ping Y, Li L, Xu H, Yan X, Dai H. A retrospective study of risk factors for carbapenem-resistant Klebsiella pneumoniae acquisition among ICU patients. J Infect Developing Ctries. 2016;10(03):208–13.

    Article  CAS  Google Scholar 

  18. Brusselaers N, Vogelaers D, Blot S. The rising problem of antimicrobial resistance in the intensive care unit. Ann Intensiv Care. 2011;1(1):1–7.

    Article  Google Scholar 

  19. Ghanbarinasab F, Haeili M, Ghanati SN, Moghimi M. High prevalence of OXA-48-like and NDM carbapenemases among carbapenem resistant Klebsiella pneumoniae of clinical origin from Iran. Iran J Microbiol. 2023;15(5):609–15.

    PubMed  PubMed Central  Google Scholar 

  20. Pajand O, Rahimi H, Badmasti F, Gholami F, Alipour T, Darabi N, et al. Various arrangements of mobile genetic elements among CC147 subpopulations of Klebsiella pneumoniae harboring bla(NDM-1): a comparative genomic analysis of carbapenem resistant strains. J Biomed Sci. 2023;30(1):73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ghotaslou R, Salahi B, Naderi G, Alizadeh N. High frequency of bla(OXA-48like) producing Klebsiella pneumoniae isolated from nosocomial infection in Azerbaijan, Iran. Infect Chemother. 2023;55(1):90–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Aslani S, Kiaei S, Afgar A, Morones-Ramírez JR, Aratboni HA, Faridi A et al. Determination of incompatibility group plasmids and copy number of the bla (NDM-1) gene in carbapenem-resistant Klebsiella pneumoniae strains recovered from different hospitals in Kerman, Iran. J Med Microbiol. 2021;70(5).

  23. Osama D, El-Mahallawy H, Mansour MT, Hashem A, Attia AS. Molecular characterization of carbapenemase-producing Klebsiella pneumoniae isolated from Egyptian Pediatric Cancer patients including a strain with a rare gene-combination of β-Lactamases. Infect Drug Resist. 2021;14:335–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Darda VM, Iosifidis E, Antachopoulos C, Volakli E, Haidich AB, Vagdatli E, et al. Risk factors for carbapenem resistance and outcomes when treating bloodstream infections in a paediatric intensive care unit. Acta Paediatr. 2019;108(10):1923–4.

    Article  PubMed  Google Scholar 

  25. Celikbilek N, Unaldi O, Kirca F, Gozalan A, Acikgoz ZC, Durmaz R. Molecular characterization of carbapenem-resistant Klebsiella pneumoniae species isolated from a Tertiary Hospital, Ankara, Turkey. Jundishapur J Microbiol. 2017;10(10).

  26. Tao G, Tan H, Ma J, Chen Q. Resistance Phenotype and molecular epidemiology of Carbapenem-resistant Klebsiella pneumoniae isolated from Nanjing Children’s Hospital in Jiangsu Province, China. Infect Drug Resist. 2022;15:5435–47.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mahmoudi S, Pourakbari B, Rahbarimanesh A, Abdosalehi MR, Ghadiri K, Mamishi S. An outbreak of ESBL-producing Klebsiella pneumoniae in an Iranian Referral Hospital: epidemiology and molecular typing. Infect Disord Drug Targets. 2019;19(1):46–54.

    Article  CAS  PubMed  Google Scholar 

Download references


Not applicable.


This study was was supported by a grant (grant number: 98-02-88-43525) from Tehran University of Medical Sciences to Dr. Shima Mahmoudi. Work of SM2 was partially supported by the European Commission- European Research Executive Agency (REA) under grant agreement No. 101130873.

Author information

Authors and Affiliations



SM2 had the idea for and designed the study and had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. SM1, SM2, and BP, contributed to the case finding. RHS and SP performed the experimental tests. SP assisted in drafting the initial manuscript. SM2 performed genotyping analysis, prepared figures and wrote the manuscript. All authors contributed to data acquisition, and reviewed the final version. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shima Mahmoudi.

Ethics declarations

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pourakbari, B., Mamishi, S., Poormohammadi, S. et al. High prevalence of carbapenem resistance and clonal expansion of blaNDM gene in Klebsiella pneumoniae isolates in an Iranian referral pediatric hospital. Gut Pathog 16, 17 (2024).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: