Acinetobacter baumannii infections that are resistant to treatment: warning signs from the COVID-19 pandemic

Future MicrobiologyVol. 17, No. 17 EditorialFree AccessAcinetobacter baumannii infections that are resistant to treatment: warning signs from the COVID-19 pandemicRyan C Ellis, Elena K Roberts, Jennifer T Grier & Steven E FiesterRyan C EllisDepartment of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC 29605, USASearch for more papers by this author, Elena K RobertsDepartment of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC 29605, USASearch for more papers by this author, Jennifer T GrierDepartment of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC 29605, USASearch for more papers by this author & Steven E Fiester*Author for correspondence: E-mail Address: stevenfiester@gmail.comDepartment of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC 29605, USADepartment of Pathology, Prisma Health Upstate, Greenville, SC 29605, USASearch for more papers by this authorPublished Online:6 Oct 2022https://doi.org/10.2217/fmb-2022-0153AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: Acinetobacterco-infectionCOVID-19drug resistanceSARS-CoV-2secondary infectionThe COVID-19 pandemic generated optimal conditions for patients to acquire secondary infections from opportunistic, drug-resistant pathogens, such as Acinetobacter baumannii. A ubiquitous, biofilm-producing Gram-negative coccobacillus, A. baumannii grows readily in moist clinical environments including respiratory equipment, humidifiers and intravenous catheters, characteristics that lend to this bacterium being one of the leading causes of ventilator-associated pneumonia in humans and to its association with SARS-CoV-2 infection. Recent studies suggest that A. baumannii possesses the highest rate of antimicrobial resistance to first-line agents, such as broad spectrum cephalosporins and carbapenems, among bacteremia-causing Gram-negative species [1]. Adding to this concern is the observation that A. baumannii is commonly found among the skin flora of hospitalized patients, patients in long-term care facilities as well as healthcare workers and is readily transmitted between healthcare environments through fomites [2,3]. The growing incidence of infections caused by multidrug-resistant A. baumannii (MDRAB), coupled with a lack of new effective antimicrobials for treatment and this pathogen’s presence in the hospital setting, constitute an urgent public health concern that is critical to address immediately, particularly given the increasing incidence of MDRAB co-infection in patients with SARS-CoV-2 [4].Of the Acinetobacter genus, A. baumannii is responsible for the majority of antimicrobial-resistant human infections [5]. Its virulence is attributed in part to its biofilm production [2], and its ability to survive for weeks in acidic, dry and low temperature environments, allowing it to readily colonize and invade ischemic and necrotic tissues. Healthcare-associated A. baumannii infections are often associated with critical illness, current/prior ICU admission, bedridden status, prior MRSA colonization, prior antibiotic use (especially β-lactams and/or fluoroquinolones), presence of intravenous catheters, mechanical ventilation and/or recent surgery [6,7], many of which are associated with hospitalization for SARS-CoV-2 infection. While ventilator-associated pneumonia is the most commonly reported type of nosocomial A. baumannii infection, representing between 3 and 7% of ventilator-associated pneumonia, A. baumannii can also cause sepsis secondary to intravascular catheter usage, surgical site infections, urinary tract infection secondary to indwelling catheters, meningitis associated with recent neurosurgery and soft tissue infections associated with burns. Approximately 12,000 Acinetobacter infections occur in the USA annually, resulting in more than 500 deaths [8]. While community-acquired A. baumannii infections are exceedingly rare in the USA, they are found in tropical climates such as Southeast Asia, Australia and the Middle East [9,10]. As such, effective treatments for A. baumannii infections should be a priority for research and development of new antimicrobials and should be paired with strategies to minimize transmission in hospital and community-based settings.Acinetobacter boasts many mechanisms for antimicrobial resistance, which has caused increasing concern for multidrug-resistant infections. Typical first-line treatments for susceptible A. baumannii infections include broad spectrum cephalosporins (ceftazidime or cefepime), combination β-lactams and β-lactamase-inhibitors (ampicillin-sulbactam), or carbapenems (imipenem or meropenem), the last of which is typically reserved for strains that are resistant to other first-line measures. However, a 2018 study demonstrated that, among bacteremia-causing Gram-negative species, A. baumannii demonstrated the highest rate of resistance to first-line agents at 18.3% of isolates (n = 999) [1]. In 2017, it was estimated that carbapenem-resistant Acinetobacter infections caused 8500 hospitalizations, 700 deaths and $281 million in attributable healthcare costs in the USA alone [8]. In the setting of MDRAB, treatment choices are limited to polymyxins or tigecycline with increasing rates of colistin-resistant A. baumannii being reported [11]. Furthermore, use of tigecycline for MDRAB has been associated with increased all-cause mortality in a meta-analysis of clinical trials utilizing this agent [12], and resistance has been reported [13]. Few new effective antibiotics have been identified for MDRAB, which prompted the WHO to list Acinetobacter as a ‘critical priority’ in its list of antibiotic resistant nosocomial pathogens requiring increased research and development of novel therapeutics [14]. In 2019, the US CDC also upgraded Acinetobacter from a ‘serious’ to ‘urgent threat’ due to increasing rates of carbapenem-resistance [8]. Although carbapenem-resistant Acinetobacter cases have been decreasing since 2012, the ‘urgent’ status of Acinetobacter reflects both a lack of novel antimicrobials in the development pipeline and an increase in Acinetobacter strains capable of producing and transferring carbapenemases to other pathogens [8].The SARS-CoV-2 pandemic has had a monumental impact on public health globally. Adding to this impact are SARS-CoV-2 bacterial co-infections and/or secondary infections, such as those caused by A. baumannii, that have increased the severity and risks associated with SARS-CoV-2 infection. Prevalence of co-infections and secondary infections in SARS-CoV-2 patients have been reported to range from 0.6 to 45% globally [15]. As patients were hospitalized with SARS-CoV-2 symptoms, prophylactic antibiotics were often prescribed in hopes they would decrease bacterial secondary or co-infections and thus reduce the risk of worsening complications and/or mortality. Alarmingly; however, a study demonstrated that 70% of hospitalized patients in the USA received antibiotics when only less than 7% of those patients had bacterial infections [16,17]. This uninformed prophylactic approach can be detrimental to the management of bacterial resistance as the high administration rate of antibiotics to hospitalized patients, who will not benefit from them, leads to increased bacterial resistance. It is essential that we be more diligent in effective antibiotic stewardship to slow and ultimately reduce the rise in bacterial antibiotic resistance. Without substantial changes in antibiotic prescribing practices, antimicrobial-resistant bacterial infections will become much harder to treat and eliminate, which in turn will lead to worsening health outcomes.Bacteria co-infections and secondary infections can play a major role in SARS-CoV-2 patient morbidity and mortality. Bacterial co-infections and secondary infections were reported to be 3.5 and 14.3%, respectively [17]. A study of 1055 patients diagnosed with SARS-CoV-2 demonstrated that in blood cultures A. baumannii was present in 27.5% of cases and 33.3% of cases with respect to respiratory cultures [18,19]. A study examining carbapenem-resistance in A. baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli between 2009 and 2013 demonstrated that A. baumannii represented 22% of carbapenem-resistant infections in US hospitals [20]. A study from Wuhan, China during the SARS-CoV-2 pandemic demonstrated that A. baumannii was the most common bacterial secondary infection with 91.2% of isolates being resistant to carbapenem. As we strive to prevent and manage SARS-CoV-2 disease, we must stay cognizant of the impact that secondary infections with antibiotic-resistant A. baumannii have on worsening health outcomes.In summary, as we continue to address the growing threat of MDR organisms, it is crucial to stay cognizant of the implications of these pathogens in the setting of SARS-CoV-2 co-infections and secondary infections. With such a high risk of antibiotic resistance in A. baumannii, we cannot continue to ignore the need to prioritize basic and applied research to generate novel treatment options for this bacterium. Without investment in this research, we will face an even greater negative impact on our society’s health and well-being from MDR A. baumannii during the ongoing and future pandemics.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.References1. Kadri SS, Adjemian J, Lai YL et al. Difficult-to-treat resistance in Gram-negative bacteremia at 173 US hospitals: retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents. Clin. Infect. Dis. 67(12), 1803–1814 (2018).Medline, Google Scholar2. 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Open Forum Infectious Diseases 4(3), ofx176 (2017).Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited ByAcinetobacter baumannii during COVID-19: What Is the Real Pandemic?27 December 2022 | Pathogens, Vol. 12, No. 1 Vol. 17, No. 17 Follow us on social media for the latest updates Metrics History Received 3 July 2022 Accepted 16 August 2022 Published online 6 October 2022 Published in print November 2022 Information© 2022 Future Medicine LtdKeywordsAcinetobacterco-infectionCOVID-19drug resistanceSARS-CoV-2secondary infectionFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download