https://orcid.org/0000-0003-2198-1947
Abstract
Objective: A troublesome implication of the COVID-19 pandemic has been an increased incidence of antimicrobial resistance. Implementation of containment measures, surveillance and monitoring of multiresistant microorganisms and/or alert organisms (MDROs_AL) should be strengthened. Here, we present the results of our observational study in which the isolation trend of MDROs_AL was compared over several quarters before and during the SARS-CoV-2 pandemic (2019-2020).
Results: Although in our hospital the number of hospital admissions decreased significantly during the SARS-CoV-2 pandemic (due to the conversion of our hospital to a COVID hospital), the incidence rate of MDRO_AL infection increased from 18.0–34.6. (incidence rate) Among the MDROs_AL, A. baumannii, carbapenem-resistant enterobacteria, staphylococci/streptococci-MLSB, intermediate/glycopeptide-resistant coagulase-negative staphylococci and vancomycin-resistant enterococci were the most represented.
Introduction
To date, the world is facing a pandemic caused by SARS-CoV-2 (Huang et al. Citation2020; Khailany et al. Citation2020; Monto and Fukuda Citation2019). Many articles on this topic and all possible issues related to COVID-19 have been published, including articles on laboratory diagnostic methods, clinical diagnosis, potential treatment methods and global vaccination campaigns (Sreepadmanabh et al. Citation2020; Vandenberg et al. Citation2021). Several authors have reported that infections caused by bacteria and fungi affect mortality in COVID-positive patients (Li et al. Citation2020; Cox et al. Citation2020). However, the reported incidence of coinfection is variable (Ruan et al. Citation2020; Lansbury et al. Citation2020). Fearing that coinfection may occur, antimicrobial therapy is widely used as part of clinical care (Rusic et al. Citation2021). However, the empirical use of antibiotics is not always useful for COVID-positive patients (Wang et al. Citation2020; Du et al. Citation2020; Wu et al. Citation2020). The adverse consequence of the heavy use of antimicrobials is the increase in antimicrobial resistance (AMR) (No Authors Citation2020; Hsu Citation2020; Reardon Citation2020; Monnet Dominique and Stephan Citation2020; Schwierzeck Citation2020; Nori et al. Citation2020; Porretta et al. Citation2020; Tiri et al. Citation2020). AMR has required urgent global action, but because the world is in a pandemic, this issue is imperative (No Authors Citation2020). The massive use of biocides for environmental hygiene in the pandemic has also impacted AMR (Rezasoltani et al. Citation2020; Knight et al. Citation2021). In our hospital, we also helped reduce the burden of AMR, especially in the second half of 2020. To investigate this aspect, we compared the data of two observational periods for each year as follows: March-May (2019 and 2020) and October-December (2019 and 2020). The choice of the two observational periods coincided with the two quarters in which Italy experienced the first and second waves of COVID, and we compared them with the same quarter of the previous COVID-free year. In the present study, we compared these data, which involved the observation of the main resistance phenotypes [i.e. multidrug resistant microorganism and/or alert organism (MDRO_AL)] over time.
Main text
The Polyclinic of the University of Rome ‘Tor Vergata’ is a 500-bed hospital and was converted to a COVID hospital from March to May 2020. The microbiology laboratory received specimens collected from inpatients and outpatients every day. To quickly identify alert organisms (a list is reported below) and/or hospital-acquired infections (HAIs), our hospital has been equipped with a real-time epidemiological information system called VIGIguard (bioMérieux, Marcy L’Etoille, France) since 2004. The system is a comprehensive bacteriology program for inspection management and statistical/epidemiological analysis of data as well as real-time and deferred management of hospital infections and target organisms. VIGIguard is connected to the Laboratory Information System (LIS; IL Werfen), which allows VIGIguard to receive all examinations requested by clinicians in the ward and collects them in the LIS. The LIS is also linked with the automated systems used in our laboratory (Vitek2, bioMérieux; MICRO MIB and MALDI TOF MS, Brucker Daltonics) to perform microbial identification and antimicrobial susceptibility testing of the isolates. Therefore, VIGIguard is currently used for statistical evaluation of antimicrobial resistance trends or the circulation of alert organisms (Fontana et al. Citation2007). For blood culture processing (BC), blood specimens are collected in BacT/ALERT FN Plus and BacT/ALERT FA Plus vials and incubated in the Virtuo system until they become positive or until they become negative for up to 5 days (bioMérieux; Marcy l’Etoile, France). The broth of positive BCs was cultured on agar plate medium, and MALDI TOF MS was used to identify the growing microorganisms (Suh and Lee Citation2021). Table shows the trends recorded in the resistance phenotype/alert organism (MDRO_AL) observed in the four quarters. The incidence of the total number of MDRO_AL recorded by VIGIguard was calculated using the admissions of each observation period (1st to 4th) in our hospital, which were 4129, 3995, 2218 and 2783, respectively. In detail, we calculated the number of infections due to MDROs_AL divided by the number of those at risk of infection during a given period and multiplied by 100.
Table 1. Multidrug Resistant Microorganisms and/or Alert Organism (MDRO_AL) observed in different quarters before and during SARS-CoV-2 pandemic (2019-2020).
Although the number of hospital admissions has decreased significantly, the incidence rate of infection due to MDROs_AL has increased from 18.0–34.6 due to the conversion of our hospital to a COVID hospital. The comparison of the proportions of MDROs_AL recorded in the different periods was performed using a two-tailed Fisher’s exact test and was 0.00001 (Table ). Differences were considered significant when p ≤ 0.05.
In particular, gram-negative pathogens were associated with an increase in A. baumannii and carbapenem-resistant enterobacteria (CRE), while gram-positive bacteria were associated with an increase in staphylococci/streptococci-MLSB (MLSB), coagulase-negative staphylococci (CONS) resistant I/R to glycopeptides and enterococci vancomycin-resistant (VRE). CONS were mainly observed from blood cultures (BC), and most isolates were considered contaminants. In our ICU, we found that the contamination rate increased from 3.6% to 12.3% (data not shown). Le Rose et al. also reported an enormous burden on blood culture contamination and central line associated bloodstream infection (CLABSI) rates during COVID (LeRose et al. Citation2020). These findings may be explained by the requirement of staff to wear personal protective suits due to COVID-19, which restrict movements, thereby reducing the compliance with the asepsis rules during the sampling process. Related to this is the increase in CRE-resistant ceftazidime/avibactam (CAZ-AVI), which is mainly attributed to KPC producers of K. pneumoniae (Table ). In a recent study, Venditti et al. emphasized that different mutations occur during treatment, including single amino acid substitutions, insertions or deletions in the blaKPC gene, and they indicated that these mutations can cause resistance to CAZ-AVI (27). Finally, by observing the defined daily dose (DDD) of certain drugs and/or certain classes of antibiotics, we concluded that the resistance trend of CAZ-AVI was consistent with the increase in drug consumption (from 300 DDD to 853 DDD over time) (Table ). The increase in glycopeptide prescriptions also impacted VRE. The large-scale use of macrolide drugs, especially in the first quarter of the COVID pandemic, may have worsened the dynamics of macrolide-lincosamide-streptogramin B (MLSB) resistant phenotypes. We also recorded some cases of aspergillosis, which have also been reported in the literature as a complication of COVID infection (Venditti et al. Citation2021; Blaize et al. Citation2020).
Table 2. Enterobacteria resistant to ceftazidime/avibactam isolates over the time.
Table 3. DDD of some target-antibiotics in different quarters before and during SARS-CoV-2 pandemic (2019-2020).
In conclusion, as reported by many authors, COVID is not only a life-threatening infection but has also resulted in the unjustified use of antibiotics in empirical cases for fear of bacterial overinfection that complicates COVID pneumonia due to a reduction in infection control practices justified by the workload caused by the pandemic. Because we are witnessing a surge in AMR, we need to implement all possible containment measures to prevent AMR from becoming a devastating future pandemic to be addressed (Getahun et al. Citation2021).
Limitation
A possible limitation of our study is that it was based on an analysis of data from a passive surveillance system. To obtain a more effective analysis of the trend of MDRO data, active surveillance, which provides the most accurate and timely information, would be recommended. In our hospital, rectal sampling to study the carriage of colon pathogens (carbapenem-resistant enterobacteria and A. baumannii) has also been active since 2018, but we decided not to include these data in consideration of the fact that we cannot be sure that sampling was punctual at all times due to the emergency caused by SARS CoV-2.
List of abbreviations
| AMR | = | antimicrobial resistance |
| MDROs | = | multidrug resistant microorganisms |
| AL | = | alert organism |
| MDR | = | multidrug resistant |
| HAI | = | hospital-acquired infections |
| CRE | = | carbapenem-resistant enterobacteria |
| MLSB | = | Staphylococci/streptococci-MLSB (MLSB), |
| CONS | = | coagulase-negative staphylococci |
| VRE | = | enterococci vancomycin-resistant |
| DDD | = | defined daily dose |
| CAZ-AVI | = | ceftazime/avibactam |
| MRSA | = | S.aureus methycillin resistant |
| ESBL | = | Extend Spectrum beta-lactamases |
List of MDRO/alert organism recorded by VIGiguard system
ESBL, CRE, MRSA, MLSB, CAZ-AVI, VRE, CONS, MLSB, Streptococcus pneumoniae penicillin resistant (SPNE-R), Stafilococci/enterococci resistant to oxazolidinones (LNZ-R), Pseudomonas aeruginosa MDR, Acinetobacter baumannii MDR, Legionella pneumophila (LP), Clostridioides difficile (CD), Aspergillus ssp (ASP).
Ethics approval
The study has been approved by the Policlinico Tor Vergata Ethics Committee (experimentation register CEI 262/21). Due to the retrospective nature of the study, specific informed consent was waived.
Availability of data and material
Raw data were generated at Polyclinic of Tor Vergata. Derived data supporting the findings of this study are available in the public repository ScienceDB at the web site http://www.scidb.cn. Dataset of PTV. (V1). 2022. Science Data Bank. 2022-01-27. doi:10.11922/sciencedb.01464; http://www.doi.org/10.11922/sciencedb.01464.
Author’s contributions
Marco Favaro: Conceptualization - Equal, Data curation - Equal, Formal analysis - Equal, Investigation - Equal, Methodology - Equal, Project administration - Lead, Supervision - Lead, Writing-original-draft - Equal, Writing-review & editing - Lead.
Anna Altieri: Data curation - Supporting, Formal analysis - Supporting, Investigation – Supporting.
Maria Cristina Bossa: Data curation - Supporting, Formal analysis - Supporting, Investigation – Supporting.
Silvia Minelli: Data curation - Supporting, Formal analysis - Supporting, Investigation – Supporting.
Carla Fontana: Conceptualization - Equal, Data curation - Equal, Formal analysis - Equal, Investigation - Equal, Methodology - Equal, Project administration - Equal, Supervision - Lead, Validation - Equal, Visualization - Equal, Writing-original draft - Equal, Writing-review & editing – Lead.
Mariagrazia Celeste: data curation - supporting
Chiara Pennacchiotti: data curation - supporting
Loredana Sarmati: supervision - equal
Massimo Andreoni: supervision - equal
Carmela Cucchi: Data curation - Equal, Investigation - Equal,
Andrea Magrini: supervision – equal
Disclosure statement
Carla Fontana has received a research grant from Angelini and as advisory board from Pfizer. Marco Favaro has received a research grant from Alifax R&D and Adaltis s.r.l.
Consent for publication
All the authors agree the present version of the manuscript and authorize the publication
Additional information
Funding
References
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