Welcome to the Bacterial Circus: The CRE Chronicles!
Ah, antimicrobial resistance—a delightful topic that gets the blood pumping, doesn’t it? I mean, who wouldn’t want to hear about the latest in the unpredictable soap opera of carbapenem-resistant Enterobacterales (CRE)? According to the latest CHINET data—yes, that’s data, my friends, not your grandma’s knitting patterns—CRE has been throwing quite the party in China. This isn’t your typical 21st-century hoedown; no, the resistance rates for Klebsiella burrito rolls are hovering around a shocking 21.7% to 23.1%. That’s like getting hit by the bus you just waved to! 🚌💨
The Guests of Honor: CRE and Its Companions
Picture this: patients arriving at the hospital doors, clutching their chests like they just read the latest report on their favourite celebrity’s diet. But it’s serious—CRE infections come with “severe clinical manifestations” and, here’s the kicker, they’re on the WHO’s list of the three most urgent antibacterial threats. That’s like winning the unholy trinity of bad news. Next time you hear someone complaining about their Wi-Fi speed, just remember, it could be worse; they could be chatting with one of these resistant little critters!
The Mysterious Mechanism of Resistance
Now, let’s address the elephant in the room—or shall I say, the collection of tiny resistant bacteria. The sneaky mechanism of resistance here is courtesy of 16S rRNA methyltransferase (RMTase), that slippery character that’s got the whole world turning a shade of grim. When combined with our friend the extended-spectrum β-lactamases (ESBLs), we’ve got ourselves a real blockbuster movie—Resistance: The Sequel. And trust me, it’s one you don’t want to watch from the front row!
The Methodology: Scientific Sherlocking
The fine folks at Nanjing Pukou People’s Hospital took it upon themselves to investigate the molecular mysteries behind these bacterial baddies. Over three years, they gathered 180 non-repetitive Enterobacterales isolates, employing fancy gadgets like the MALDI-TOF MS. (No, that’s not a new band, but it does sound cool, right?) Each strain was scrutinized like a contestant on a cooking show, but instead of “What’s your secret ingredient?” the question was, “Which resistance gene is your deadly cum laude?”
Results: The Showdown of Strains
At the end of the day, K. pneumoniae was the star of the show, accounting for an astounding 50.1% of the isolates. You could say it was the Kardashian of the CRE world—unwanted but impossible to ignore. The party continued with E. coli at 30.6%. From sputum to urine, these isolates were collected like Pokémon cards—except nobody is trading these bad boys!
Resistance Rates: The Unfortunate Truth
But hang on! Just when you thought it couldn’t get worse, we learn that 87.8% of the 180 CRE isolates showed resistance to at least one aminoglycoside drug. It’s like that annoying friend who just won’t leave the party, despite your best efforts to hint that it’s time to go home. “Oh no, you can’t just lock the door!” said the CRE. Well, who said antibiotics weren’t dramatic?
The Future is Looking… Dicey?
Here’s where it gets really interesting. With a positive rate of 63.3% for the 16S rRNA methyltransferase gene among CRE strains, primarily rmtB, we’re staring down the barrel of a continuing war. The character drama between blaKPC and rmtB is one that doctors are going to need to navigate carefully—much like trying to pick the right wine to complement ancient Egyptian artifacts at a dinner party.
Conclusion: Hitting The Reset Button
So, what’s the takeaway here? The detection of 16S rRNA methyltransferase genes is crucial for anyone dealing with these fearsome foes. With these genes lounging around like they own the place, effective treatment will need to be a blend of caution and scientific hospitality. Let’s be clear: this isn’t just an isolated issue. CRE is the boisterous neighbor that keeps crashing parties, and if we don’t monitor it closely, it’s going to claim lounge rights in hospitals worldwide!
Let’s Wrap This Up
In summary, carbapenem-resistant Enterobacterales are no joke—they’re here, they’re multiplying, and until we develop a strike force of antibiotics and smart healthcare strategies, we might be looking at a full-blown clinical crisis. So, the next time you come down with a sniffle and think about accessing healthcare, just remember: you might be dodging more than just a cold. You might be tangling with the charming but lethal CRE. Now, that is something to sneeze at!
Ethics and Disclosure
Rest assured, everything’s been ethically approved, and the authors here have absolutely no conflict of interest—unless we’re talking about a heated debate over who left the empty coffee pot in the break room.
Acknowledgments
A shoutout is in order for the folks who funded this marvelous escapade of research. They’re not just counting their pennies; they’re out there saving lives one study at a time!
References
Just in case I’ve whetted your appetite for knowledge, you can check out all the juicy references that built this whole narrative. After all, what’s a party without some intellectual appetizers?
Introduction
The most recent data from CHINET has highlighted a concerning trend in China regarding the isolation rate of carbapenem-resistant Enterobacterales (CRE). In recent years, this rate has remained alarmingly elevated, especially for Klebsiella species, which show a resistance to carbapenems ranging between 21.7% and 23.1%1. This persistent antibiotic resistance poses a significant threat to patient care, as infections caused by CRE are associated with severe clinical complications and notably high mortality rates. The World Health Organization has categorized CRE as one of the top three urgent threats related to antimicrobial resistance2. Furthermore, data derived from the China Antimicrobial Resistance Surveillance Network indicates that Escherichia coli and Enterobacter cloacae, among other Enterobacteriaceae, exhibit a high level of susceptibility to specific antibiotics, such as aztreonam-avibactam, amikacin, colistin, and tigecycline, with sensitivity rates ranging from 87.1% to 95.5%3. Clinicians are advised to consider aminoglycosides, colistin, and tigecycline, either singly or in combination, as recommended treatments for CRE infections4. Research suggests that employing a combination of aminoglycosides may enhance therapeutic outcomes for patients with CRE5. However, the emerging presence of 16S rRNA methyltransferase (RMTase) is contributing to high-level resistance to aminoglycosides globally. RMTase often coexists with extended-spectrum β-lactamases (ESBLs) or carbapenemases,7. This situation complicates the management of infectious diseases and the control of multidrug-resistant bacteria, as resistance patterns can vary significantly across different regions. This study aims to explore the molecular epidemiology of 16S rRNA methyltransferase genes in CRE strains isolated from Nanjing hospitals to better assess their prevalence and guide clinicians toward more rational and scientific drug use, while also formulating effective preventive measures.
Materials and Methods
Species Identification, Antimicrobial Susceptibility Testing, and Confirmation of Carbapenemase Production
A total of 180 non-repetitive carbapenem-resistant Enterobacterales isolates were collected at Nanjing Pukou People’s Hospital over a three-year period spanning January 2020 to December 2022. All isolates underwent reidentification utilizing MALDI-TOF MS (bioMérieux, France). Antimicrobial susceptibility testing was completed using the VITEK-2 COMPACT system (bioMérieux, France). CRE isolates were defined as strains with resistance to either imipenem or meropenem, exhibiting a minimum inhibitory concentration (MIC) of 4μg/mL. The presence of carbapenemase genes, including KPC, NDM, OXA, IMP, and VIM, was confirmed via PCR. Quality control and interpretation of results adhered to the 2020 CLSI breakpoints for all antimicrobial agents, excluding tigecycline, for which the European Committee for Antimicrobial Susceptibility Testing (EUCAST) criteria were utilized. Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 served as quality control strains.
Statistical Analysis of Data
WHONET 5.6 and SPSS software (version 22.0) were employed for data analysis. The WHONET 5.6 software facilitated the evaluation of bacterial drug susceptibility results, while Chi-square tests were implemented to assess the association between various groups of CRE isolates.
Results
General Characteristics of CRE Isolates
Following the elimination of duplicate strains, 180 distinct CRE strains were identified at the studied hospital from January 2020 to December 2022. Among these, K. pneumoniae represented the largest fraction at 50.1% (91/180), succeeded by E. coli at 30.6% (55/180), E. cloacae at 7.2% (13/180), P. mirabilis at 5.6% (10/180), S. marcescens at 3.3% (6/180), C. freundii at 1.7% (3/180), and K. aerogenes at 1.1% (2/180)(Figure 1a). The strains were isolated from various clinical specimens, with a majority obtained from sputum (47.22%), urine (30.00%), and bronchoalveolar lavage fluid (14.44%), as well as smaller percentages from venous blood (5.56%), purulent secretion (1.67%), pleural effusion (0.56%), and ascites (0.56%)(Figure 1b).
Prevalence of Genes in CRE
PCR analysis identified that 63.3% (114/180) of the CRE isolates harbored at least one 16S rRNA methylase gene, with rmtB, armA, and rmtA being detected in 80, 26, and 5 strains respectively. The combination of rmtB and armA was observed in three strains. However, rmtC, rmtD, rmtE, and npmA were absent in all tested strains. Based on the presence of 16S rRNA methylase genes, CRE strains were categorized into two groups: those positive for the genes and those negative. Carbapenemase genes were identified in 175 out of the 180 CRE strains, including blaKPC (n= 115), blaNDM (n = 43), blaIMP (n = 5), blaNDM+blaKPC (n = 11), and blaIMP+blaKPC (n = 1). When compared to 16S rRNA methylase genes-negative CRE strains, positive strains exhibited a significantly higher presence of blaKPC and a lower presence of blaNDM, with P values of 0.034 and 0.003 respectively (Tables 2–4) (Figure 2).
Antibiotic Susceptibilities of CRE
Among the 180 CRE isolates, a significant 87.8% (158) were resistant to at least one aminoglycoside antibiotic. Resistance rates for gentamicin, tobramycin, and amikacin were reported at 85.0% (153/180), 82.8% (149/180), and 54.4% (98/180) respectively. Notably, all 98 amikacin-resistant strains were also resistant to gentamicin and tobramycin. In contrast, 16S rRNA methylase genes-positive isolates demonstrated higher susceptibility to trimethoprim-sulfamethoxazole, tetracycline, and minocycline, but exhibited heightened resistance to amikacin, gentamicin, tobramycin, aztreonam, and ciprofloxacin (P Table 5).
Discussion
Carbapenems are critical as last-line antibiotics for treating multidrug-resistant (MDR) gram-negative infections, yet the growing utilization of these drugs has led to a widespread emergence of CRE strains globally12. Patients infected with CRE have shown a markedly higher risk of mortality than those with carbapenem-sensitive strains13. Existing studies confirm that the combination of tigecycline with aminoglycosides like amikacin or gentamicin exhibits a synergistic effect against CRE infections in both laboratory and animal testing, indicating that this combination therapy may represent a promising strategy for management14. Nevertheless, 16S rRNA methylases have emerged as significant contributors to aminoglycoside resistance. These enzymes, by methylating the target site of aminoglycosides (16S rRNA), facilitate high-level and extensive resistance against all clinically relevant aminoglycosides. The resistance mechanism occurs when a 3CH motif provided by S-adenosylmethionine (SAM) is added to specific residues within the A-site of 16S rRNA, catalyzed by 16S RMTase. This modification results in a notable reduction in aminoglycoside binding affinity to the methylated 16S rRNA, thus leading to widespread and high-level resistance15. The presence of 16S rRNA methyltransferase across numerous countries among Gram-negative bacteria highlights the global urgency posed by this resistance mechanism16.
Conclusion
In our research, we determined that the prevalence of the 16S rRNA methyltransferase gene among CRE strains was notably high at 63.3%, primarily associated with the rmtB genotype. These strains demonstrated a greater presence of blaKPC carbapenemase genes. These findings imply that the coexistence of blaKPC and the rmtB genes serve as principal resistance mechanisms for Enterobacterales against both carbapenems and aminoglycosides within our hospital. The mobility of the 16S rRNA methyltransferase gene in plasmids and transposons allows it to transcend geographic boundaries, marrying with other resistance genes. Thus, robust monitoring and epidemiological studies concerning the 16S rRNA methyltransferase gene and its resistance mechanisms are crucial for informing clinical drug use.
Ethics Approval and Consent to Participate
The clinical isolates utilized in our study were obtained as a part of routine hospital procedures, and the study received approval from the Medical Science Research Ethics Committee of the Nanjing Pukou People’s Hospital (2022-SR-017, approved 28 April 2022).
Acknowledgments
This work was supported by the Natural Science Foundation of Ningxia (2024AAC03642), the Nanjing Pukou People’s Hospital Project (KJ2022-19), the Open Project Funding Projects from the Ningxia Key Laboratory of Clinical and Pathogenic Microbiology (MKLG-2024-13), and the Medical Young Backbone Talent Project of the General Hospital of Ningxia Medical University.
Disclosure
The authors declare that they have no conflict of interest.
References
1. Yan GUO, Fupin HU, Demei ZHU, et al. Surveillance of bacterial resistance in tertiary hospitals across China: results of CHINET antimicrobial resistance surveillance program in 2022. J Infect Chemother. 2024;24(03):277–286.
2. WHO. Global priority list of antibiotic resistant bacteria to guide research, discovery, and development of new antibiotics[R/OL]. Available From: https://www.whoint/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed. Accessed November 19, 2024.
3. China Antimicrobial Resistance Surveillance Network. Antimicrobial susceptibility, resistance mechanisms, and molecular characteristics of carbapenem-resistant Enterobacterales (except K.pneumoniae) in China. J Infect Chemother. 2024;24(05):537–544.
4. Xu Y, Gu B, Huang M, et al. Epidemiology of carbapenem resistant Enterobacteriaceae(CRE) during 2000-2012 in Asia. Asia J Thorac Dis. 2015;7(3):376–385.
5. WANG Minggui. Strategy for diagnosis and treatment of carbapenem-resistant gram-negative bacterial infections. Chin J Infect Chemother. 2024;24(2):133–134.
6. Gutiérrez-Gutiérrez B, Salamanca E, De Cueto M, et al. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT):a retrospective cohort study. Lancet Infect Dis. 2017;17(7):726–734. doi:10.1016/S1473-3099(17)30228-1
7. Shen X, Liu L, Yu J, et al. High prevalence of 16S rRNA methyltransferase genes in carbapenem-resistant Klebsiella pneumoniae clinical isolates associated with bloodstream infections in 11 Chinese teaching hospitals. Infect Drug Resist. 2020;13:2189–2197. doi:10.2147/IDR.S254479
What are the common resistance genes found in carbapenem-resistant Enterobacterales (CRE) isolates?
The provided text discusses a study on the prevalence of carbapenem-resistant Enterobacterales (CRE) and the associated resistance genes in clinical isolates. Key findings and sections of the text can be summarized as follows:
### Key Findings:
1. **Prevalence of CRE Strains**:
– The study identified CRE strains from various clinical specimens, primarily sputum (47.22%), urine (30.00%), and bronchoalveolar lavage fluid (14.44%).
– Specific bacterial strains included **K. pneumoniae** at 1.7% (3/180) and **K. aerogenes** at 1.1% (2/180).
2. **Resistance Genes**:
- PCR analysis showed that 63.3% (114/180) of CRE isolates harbored at least one 16S rRNA methylase gene, with **rmtB** being the most common (80 strains), followed by **armA** (26 strains) and **rmtA** (5 strains).
– Carbapenemase genes were prevalent, identified in 175 CRE strains, including **blaKPC** (115), **blaNDM** (43), and **blaIMP** (5).
3. **Antibiotic Susceptibilities**:
– A significant 87.8% (158/180) of CRE isolates were resistant to at least one aminoglycoside antibiotic, with gentamicin resistance at 85%, tobramycin at 82.8%, and amikacin at 54.4%.
– Strains positive for 16S rRNA methylase genes showed higher susceptibility to certain antibiotics like trimethoprim-sulfamethoxazole but had increased resistance to aminoglycosides.
4. **Clinical Implications**:
– CRE infections are linked with higher mortality compared to carbapenem-sensitive infections.
– The study highlights the importance of monitoring antibiotic resistance mechanisms in clinical settings due to the mobility of resistance genes.
### Discussion:
- The emergence of CRE strains globally is alarming, particularly as carbapenems are crucial last-line treatments for multidrug-resistant infections.
– Combining tigecycline with aminoglycosides has shown promise, but the presence of 16S rRNA methylases complicates treatment due to high-level resistance to aminoglycosides.
### Conclusion:
– The high prevalence of the 16S rRNA methyltransferase gene in CRE strains, particularly associated with the **rmtB** genotype and **blaKPC** carbapenemase genes, indicates critical resistance mechanisms in Enterobacterales.
– Continuous surveillance and research on resistance mechanisms are essential for improving clinical treatment strategies.
### Ethics Approval:
– The study received approval from the Medical Science Research Ethics Committee of the Nanjing Pukou People’s Hospital.
### Acknowledgments and Funding:
– The research was supported by multiple funding sources including the Natural Science Foundation of Ningxia and local hospital projects.
### Conflict of Interest:
– The authors declared no conflict of interest.
### References:
– The text contains references to publication and guidelines by WHO and other studies related to antimicrobial resistance.
This summary encapsulates the primary findings and implications of the research article regarding CRE and its resistance mechanisms, underlining the urgency for continued monitoring and strategic therapeutic interventions.
