Multidrug-resistant infection in COVID-19 patients: A meta-analysis

Yeonju La et al. reported the most problematic multidrug-resistant microorganisms (MDROs) increased after the Coronavirus disease 2019 (COVID-19) pandemic in South Korea, suggesting active and continuous monitoring of the increase in infections with MDROs.1La Y. et al.Increase of multidrug-resistant bacteria after the COVID-19 pandemic in South Korea: time-series analyses of a long-term multicenter cohort.J. Infect. 2022; (Sep 30:S0163-4453(22)00556-4)Google Scholar We had a valuable opportunity to carefully read this interesting manuscript and additional published studies to further explore the infection rate of multidrug-resistant (MDR) in patients with COVID-19. COVID-19 is a newly emerging disease in the human population. The World Health Organization classified COVID-19 as a pandemic on March 11, 2020. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Some affected patients need hospitalization in the intensive care unit (ICU) for critical care and mechanical ventilation, increasing the risk of secondary infection. The cause of this secondary infection may be MDR bacterial infection. MDROs are defined as those resistant to one or more classes of antimicrobial drugs, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and certain Gram-negative Enterobacteriaceae, which produce ultra-broad-spectrum beta-lactamase or carbapenemase resistance. Antimicrobial resistance is recognized as a public threat of increasing urgency. By 2050, an estimated 10 million people will die annually from MDR infections (resistant to three or more antimicrobial drugs). Decreased effectiveness of antibiotics may exponentially increase the risk of medical and surgical procedures and immunosuppressive treatments such as cancer chemotherapy. In the post-pandemic era, antibiotic resistance might become a bigger challenge. In view of the great danger posed by MDR bacteria, we tried to explore the prevalence of MDR bacteria in patients with COVID-19 to provide timely and effective prevention programs. We found that some published studies explored the situation of patients with COVID-19 who acquired MDR bacteria during hospitalization. Fernández2Fernández P. et al.Colonization by multidrug-resistant microorganisms in ICU patients during the COVID-19 pandemic.Medicina. Intensiva. 2021; 45: 313-315Google Scholar et al. compared the colonization of MDROs in patients infected and uninfected with COVID-19 admitted to the ICU during the COVID-19 epidemic. It was concluded that the non-COVID-19 group in the ICU had a lower rate of MDR bacterial infections after admission than the COVID-19 group. Not only in the ICU, the use of mechanical ventilation also aggravated the secondary respiratory tract infection of patients with COVID-19. Patients with COVID-19 admitted to the ICU and requiring mechanical ventilation had a high rate of secondary infections during their hospital stay.3Ceballos M.E. et al.Secondary respiratory early and late infections in mechanically ventilated patients with COVID-19.BMC. Infect. Dis. 2022; 22: 760Google Scholar Moreover, within late secondary infections, one third of the isolated bacteria were MDR. For this reason, PubMed, Web of Science, Embase, and Cochrane Library databases were extensively searched for all compliant studies published from January 1, 2020, to October 10, 2022. The inclusion criteria were as follows: (1) adult patients with COVID-19 confirmed by reverse transcriptase–polymerase chain reaction; (2) peer-reviewed original studies in English; (3) MDR-infected strains measured by the number of strains; and (4) the infection statistics of MDR based on the number of people. In total, 8 studies with 1423 patients were identified. Eight studies reported MDR bacterial infections in patients with COVID-19 pneumonia. General information about the included studies is summarized (Table 1).2Fernández P. et al.Colonization by multidrug-resistant microorganisms in ICU patients during the COVID-19 pandemic.Medicina. Intensiva. 2021; 45: 313-315Google Scholar, 3Ceballos M.E. et al.Secondary respiratory early and late infections in mechanically ventilated patients with COVID-19.BMC. Infect. Dis. 2022; 22: 760Google Scholar, 4Bhargava A. et al.High rate of multidrug-resistant organisms (MDROs) among COVID-19 patients presenting with bacteremia upon hospital admission.Am. J. Infect. Control. 2021; 49: 1441-1442Google Scholar, 5Bogossian E.G. et al.The acquisition of multidrug-resistant bacteria in patients admitted to COVID-19 intensive care units: a monocentric retrospective case control study.Microorganisms. 2020; 8: 1821Google Scholar, 6de Hesselle M.L. et al.Invasiveness of ventilation therapy is associated to prevalence of secondary bacterial and fungal infections in critically ill COVID-19 patients.J. Clin. Med. 2022; 11: 5239Google Scholar, 7Nori P. et al.Bacterial and fungal coinfections in COVID-19 patients hospitalized during the New York City pandemic surge.Infect. Control. Hospital. Epidemiol. 2021; 42: 84-88Google Scholar, 8Santoso P. et al.MDR pathogens organisms as risk factor of mortality in secondary pulmonary bacterial infections among COVID-19 patients: observational studies in two referral hospitals in West Java, Indonesia.Int. J. General. Med. 2022; 15: 4741-4751Google Scholar, 9Singulani J.L. et al.The impact of COVID-19 on antimicrobial prescription and drug resistance in fungi and bacteria.Brazil. J. Microbiol. 2022; (Sep 10): 1-11Google Scholar We focused on collecting some of the most common strains, such as Enterobacter, S. aureus, and Klebsiella pneumoniae. The results of eight studies were showed that 42% of the patients with COVID-19 were infected with MDR (95% confidence interval (CI), 0.23–0.61; P < 0.01) (Fig. 1). Also, the heterogeneity (I2) was 97.9% and the Egger value was 0.174, indicating no publication bias. We also collected data on common strains for collation to further investigate the specific strain distribution of MDR bacteria. Among the MDR strains, the K. pneumoniae rate in five studies was 21% (95% CI, 0.09–0.32; P < 0.01), the Enterobacter spp. rate in another five was 8% (95% CI, 0.04–0.12), and the S. aureus rate in five studies was 16% (95% CI, 0.05–0.28; P < 0.01). These are the main bacteria isolated from endotracheal aspirate and blood.Table 1The basic information of the included literature.AuthorYearCountryTotalMDRMDR strainsK. pneumoniaeEnterobacter spp.S. aureusMaría2022Chile7122714(5.6%)5(7%)4(5.6%)Junya L2022Brazil43283811(28.9%)2(5.3%)6(15.8%)Marie2022Europe840598NNNNAshish2021America391616N2(12.5%)11(68.8%)Prayudi2022Indonesia182747414(18.9%)N1(1.4%)Elisa2020Belgium7224318(25.8%)3(9.7%)NFernández2021Spain249135(38.5%)3(23.1%)2(15.4%)Priya2020America15224NNNNTotal: number of COVID-19 patient included in the study.MDR: Number of people infected with MDR.N: no data. Open table in a new tab Total: number of COVID-19 patient included in the study. MDR: Number of people infected with MDR. N: no data. During the COVID-19 pandemic, medical care systems worldwide became overwhelmed, and the shortage of beds and personal protective equipment (PPE) in ICU also contributed to the rapid growth of MDR bacteria. Also, the reasons for the high infection rate of MDR bacteria in patients with COVID-19 might be as follows10Gasperini B. et al.Multidrug-resistant bacterial infections in geriatric hospitalized patients before and after the COVID-19 outbreak: results from a retrospective observational study in two geriatric wards.Antibiotics. (Basel, Switzerland). 2021; 10: 95Google Scholar: (i) Cough, sore throat, and fever, which were the most common symptoms of COVID-19, were independent factors associated with overuse of antibiotics in hospitals and communities. (ii) Antimicrobial drug use was common in patients with COVID-19, and more than 70% of the patients with COVID-19 received antimicrobial treatment despite less than 10% having bacterial or fungal coinfections. (iii) At the beginning of the pandemic, some broad-spectrum antimicrobial agents were suggested as treatments against COVID-19 and were tested for a possible efficacy against SARS-CoV-2, for example, teicoplanin, azithromycin, and tetracycline. In a word, this study draws attention to the necessity of monitoring drug resistance/multidrug resistance and proper use of antibiotics, especially for patients with COVID-19 hospitalized for a long time. Nonpharmacological behavioral changes implemented during the COVID-19 pandemic to drop the spread of SARS-CoV2 may also reduce the prevalence of MDR infection in patients with COVID-19. For example, hospital hygiene habits, the improvement of PPE, and the use of antibacterial soap and disinfectant were adopted to a great extent. These practices may reduce the spread of MDR. In addition, restrictions on the number of hospital visits, the availability of nucleic acid testing, and distance policies implemented for inpatients may lead to future reductions in bacterial circulation. The authors confirm that the data supporting the findings of this study are available within the article. No potential conflict of interest was reported by the author(s). The presented study was Medical and Technology Project of Zhejiang Province (No.2021KY890); Hangzhou science and Technology Bureau fund (No.20191203B96; No.20191203B105); Clinical Research Fund of Zhejiang Medical Association(No.2020ZYC-A13); Zhejiang Kangenbei Hospital Management Soft Science Research Project (No2022ZHA-KEB316); Zhejiang Traditional Chinese Medicine Scientific Research Fund Project(No. 2022ZB280). The work was supported by the Key medical disciplines of Hangzhou.