Abstract
Background
Acinetobacter baumannii is recognized as a major threat that causes healthcare-associated infections and causes a huge challenge to the health system worldwide. This research study was designed to detect the types and profiles of antibiotics tested against A. baumannii clinical strains in Turkey to evaluate their effectiveness and reevaluate their usage.
Main body of the abstract
The study depended on data search strategy using the online electronic database. We carried out a detailed analysis to all original research articles from 2011 to 2022 all conducted in Turkey. The study involved 91 articles and revealed about 40 antibiotics tested from 2006 to 2021 against A. baumannii with a different frequency. The more frequency antibiotics tested by health institutions in Turkey during this period included 15 antibiotics which are (Amikacin, Gentamicin, Imipenem, Meropenem, Cefoperazone–sulbactam, Ceftazidime, Cefepime, Ampicillin/sulbactam, Piperacillin, Piperacillin/tazobactam, Ciprofloxacin, Levofloxacin, Trimethoprim–Sulfamethoxazole, Colistin and Tigecycline). The frequency of resistance rate with percentage of (80–100%) shown by A. baumannii against these antibiotics was as follows (40.96%, 50.64%, 77.77%, 78.31%, 46.15%, 94.11%, 88.23%, 80.85%, 95.46%, 91.93%, 93.42%, 82.85%, 53.57%, 2.66%, 3.70%), respectively. From 2016 to 2021, an increase in resistance rates by A. baumannii against Colistin and Tigecycline was indicated noticeably. The 0% resistance rates during this period against Colistin were reported in a percentage of 16.6%, while the appearance of highly noticeable resistance (from 80 to 100 = 3.70%) against Tigecycline and the continuous elevation of resistance rates against this drug was worrisome.
Short conclusion
Stability in high resistance rates against some antibiotics for the last 10 years and the increase in resistance rates against effective antibiotics by A. baumannii should undergo for more studies and re-evaluation.
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Introduction
Acinetobacter baumannii is a major threat that causing healthcare-associated infections. And because of the increasing rates of resistance and the high mortality caused by A. baumannii, as well as the lack of effective treatment options due to the very few available drugs that can control these bacteria, the world health organization has been designated this bacteria as a priority 1-critical that urgently requires a new antibiotic innovation to control them (Tacconelli et al. 2018). Serious nosocomial infections caused by A. baumannii include pulmonary, meningitis, bacteremia/sepsis, urinary tract, wound and soft tissue infections as well peritonitis, osteomyelitis, synovitis and conjunctivitis (Gedefie et al. 2021; Roy et al. 2022; Nguyen and Joshi 2021). The rate of these infections increases obviously in intensive care units (ICUs) particularly patients requiring special equipment such as mechanical ventilation, endotracheal incubators and catheters in addition to patients suffering of trauma or burn and patients who underwent a recent surgery (Falcone et al. 2021; Ababneh et al. 2022). Infections due to A. baumannii are correlated with a high rate of mortality through causing serious infections, septic shock, and deaths (Vrancianu et al. 2020; Lee et al. 2022), besides increased costs and duration of hospitalization and limited therapeutic choices especially in (ICUs) (Ibrahim et al. 2021; Mohd Sazlly Lim et al. 2019). Even with suitable treatment, the mortality rate of infections caused by these bacteria can increase highly after one month stay in hospital (Falcone et al. 2022). Although A. baumannii resistance rates are reported in a variable value from region to region, they have been developing steadily and are occurring more rapidly than the innovation of novel antibiotics. Various clinical studies comparing single therapy to combination therapies showed similar mortality rates with no significant statistical difference in clinical cure. Mortality of 30 days in combination and in the monotherapy group was 43.3% and 42.9%, respectively (Giamarellou and Karaiskos 2022). Significant increase in resistance shown by Acinetobacter species to nearly all present anti-microbial drugs makes treatment options very limited for patients with A. baumannii infection and put the health institutions around the world in great concern. Our study is designed to introduce a detailed profile of antibiotics tested against A. baumannii between 2006 and 2021 in different health associations of Turkey. The study may provide a review about the antibiotics used in the past and re-evaluate the antibiotics policies to be applied in the future.
Materials and methods
The online electronic database was searched for studies regarding A. baumannii isolated from clinical samples in health institutions of Turkey to detect the antibiotics profile of these isolates.
Search strategy
The studies were screened in PubMed, Google Scholar and Google search for articles published in English and Turkish between 2011 and 2022. During the screening process, the text words or search terms used in combinations were “Acinetobacter spp.,” “A. baumannii,” “antibiotic resistance,” “antibiotic susceptibility” and “Turkey.”
Criteria for studies
The research involved only studies that contained antibiotics profile of A. baumannii isolated from clinical samples. These studies were published in English and Turkish. Case reports, antibiotics profile of Acinetobacter spp. and antibiotics profile of A. baumannii isolated only from environmental samples are excluded from the study.
Article selection and data collection
The studies should have been conducted in Turkey, the data presented should have been published in the years 2011–2022, the language should be English or Turkish, and papers should be original research articles providing access to the full text. The contents of the articles including titles, abstracts, materials and methods, results and discussion were all examined and assessed for data extraction. We extracted the following information from the articles that was finally included: all numerical values given in the studies regarding the rates of susceptibility and resistance of all antibiotics tested through the antibiotic susceptibility test against the clinical strains of A. baumannii, Date and year of publication, Duration of study, Number of isolates, Types of samples or site of infection, Ward of isolation, Mortality rates, The institution where the study was conducted and which region in Turkey.
Results
Study characteristics of included publications
All the details of study characteristics are summarized in Table 1. The study included 91 articles carried out in Turkey. The institutions, where the studies conducted in, involved state hospitals and clinic centers which included 92 and about 67 teaching hospitals. All these health institutions were distributed in different regions of Turkey and covered 41 states of Turkey which are Adana, Adiyaman, Afyonkarahisar, Amasya, Ankara, Balikesir, Bolu, Bursa, Çanakkale, Diyarbakir, Düzce, Elaziğ, Erzurum, Gaziantep, Giresun, Isparta, İstanbul, İzmir, Kahramanmaraş, Karabük, Kayseri, Kirikkale, Kirşehir, Kocaeli, Konya, Manisa, Mardin, Mersin, Muğla, Niğde, Ordu, Rize, Sakarya, Samsun, Şanliurfa, Tekirdağ, Tokat, Trabzon, Van, Zonguldak and Kuzey Kıbrıs (Northern Cyprus). With exclusion articles that indicated different cities or institutions as a source of isolates, we found that frequency of studies was more in Ankara, Istanbul and Izmir with (13, 12, 8 articles), respectively. The studies were published between 2011 and 2022 with a frequency numbers of 3 articles in 2011, 4 in 2012, 13 in 2013, 17 in 2014, 6 in 2015, 11 in 2016, 6 in 2017, 3 in 2018, 8 in 2019, 10 in 2020, 6 in 2021 and 4 in 2022. The articles covered studies that were performed between 2006 and 2021. In 5 articles, all the years of study are included in Table 1 because of the absence of the average of resistance rates. The date of study in 3 articles was unclear, so we could not include the rates of resistance in these articles with other numbers in analysis of the results. The total of A. baumannii clinical isolates was 24,425 isolates. A. baumannii were collected from diverse clinical specimens that included bronchial lavage, tracheal aspirate, bronchial washing fluid/bronchial brushing, transbronchial biopsy, blood, wound, throat swab, urine, sputum, catheter tip, cerebrospinal fluid, thoracentesis material, pleural fluid, peritoneal fluid, aspiration fluid, ear, paracentesis fluid, skin/mucosa, exudates and discharge samples. Majority of samples were taken from hospitalized patients admitted to intensive care units.
Antibiotic resistance shown by A. baumannii clinical strains
Analysis of the 91 articles concentrated on the antibiotics tested through antibiotic susceptibility test conducted by the health institutions in Turkey from 2006 to 2021 for detecting resistance and susceptibility of A. baumannii against these antibiotics. Antibiotic susceptibility methods used in the articles included: 40 articles used automated system (30 used VITEK 2 system and 10 used Phoenix 100 system). Twenty-six articles used disk diffusion method. Thirteen articles used mixed methods (automated system and disk diffusion method). Six articles used broth microdilution method. One article used only the E-Test method, and five articles did not mention the method. The results of the antibiotic susceptibility test were interpreted based on the recommendation of the Clinical Laboratory Standards Institute (CLSI) in majority of articles 80.5%, while the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations used in 19.5%.
The antibiotics profiles extracted from the studies are detailed in Table 2. The data showed the following results.
Aminoglycosides
Amikacin, Gentamicin, Netilmicin and Tobramycin were the antibiotics of aminoglycoside group used in studies included in the research during the period from 2006 to 2021. Amikacin was used in 76 articles and Gentamycin in 70 articles, while Netilmicin and Tobramycin were used in 27 and 21 articles, respectively. Resistance rate percentages of A. baumannii against aminoglycosides were as follows.
Amikacin
2007–2012: 68.1, 86.7, 32, 40, 100, 100, 63, 70.01, 100, 64, 100, 59, 86, 100, 71.7, 62, 74, 60, 52, 73, 53, 60, 75.3, 78.9, 44, 97, 91.8, 88, 84.6, 81.8, 84.2, 65, 56, 46, 71.1, 62, 50.
2012–2016: 73, 67.1, 81, 67.5, 86.3, 85.2, 86.3, 68.1, 60.7, 35.2, 79.3, 55.7, 65.6, 100, 63, 70, 94.81, 82, 92, 89, 94.2, 91.8, 72.92, 40, 81, 53.5, 52.9, 100.
2016–2021: 53, 59.3, 79, 90.7, 55.7, 46.6, 68.2, 73.5, 12.5, 77.6, 100, 97.8, 93.3, 39.2, 87.5, 83.3, 95, 98.5, 53.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 40.97%, from 50–70 = 48.19%, < 50 = 10.84%.
Gentamicin
2007–2012: 80, 39, 100, 48, 34.16, 100, 100, 90, 67, 54, 89, 90, 74.7, 11, 10, 11, 22, 75.7, 86, 77.1, 19.3, 84, 85, 93.9, 96, 76.5, 66, 87.2, 83.4, 82.5, 59.5, 62.
2012–2016: 65, 68.6, 76.8, 87, 74.1, 75.76, 77.2, 82.1, 83.6, 72.1, 100, 69, 84.3, 86.62, 86, 69.7, 74, 92, 95.8, 100, 93.7, 47, 88, 60.5, 55.7, 100.
2016–2021: 25, 60.5, 63.5, 66.9, 50.4, 70.5, 73.5, 78.9, 100, 95.7, 86, 89, 92.9, 93.2, 87.5, 82.3, 83.3, 90.7, 74.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 50.65%, from 50–70 = 36.36%, < 50 = 12.99%.
Netilmicin
2007–2012: 54.2, 39, 0, 89, 0, 6, 26.6, 13.7, 55, 41.7, 52.1, 57.6, 53, 57.
2012–2016: 36, 85.2, 58.7, 19.5, 97.2, 27.8, 94.3, 21, 36.
2016–2019: 92, 43.3, 72.7, 79.4, 75.8.
2019–2021: no data found.
The total percentage of resistance rates frequency appears as follows:
From 80–100 = 17.85%, from 50–70 = 35.72%, < 50 = 46.43%
Tobramycin
2007–2012: 36.3, 40.56, 58, 36.5, 55, 21.1, 84, 54.2, 54, 46.3, 68.1, 22.9.
2012–2016: 100, 37.8, 25.4, 0, 78, 100.
2016–2021: 47.5, 60.8, 100, 67.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 18.18%, from 50–70 = 36.36%, < 50 = 45.46%.
Carbapenems
Doripenem, Ertapenem, Imipenem and Meropenem were the antibiotics of Carbapenem group used in studies included in the research during the period from 2006 to 2021. Imipenem was found in 72 articles and Meropenem in 74 articles, while Ertapenem was found in 2 articles and Doripenem in 1 article. Resistance rate percentages of A. baumannii against Carbapenems were as follows.
Imipenem
2007–2012: 91.7, 53.3, 86, 20, 100, 100, 95, 80.07, 100, 71, 92, 100, 91, 57, 72.1, 50, 77, 78, 80, 70.2, 86, 74.5, 91.9, 93, 91, 100, 54, 92.3, 94.4, 98.9, 91.5, 100, 87.5, 100, 61.5, 74.3, 81.5, 100.
2012–2016: 100, 100, 73.2, 100, 91.3, 80, 90.91, 89.1, 91.1, 94.9, 73.8, 100, 84, 94.3, 98.5, 96, 100, 98, 97.1, 94.2, 99.4, 100, 95, 100, 95.3, 100, 100.
2016–2021: 73.7, 96, 94.4, 72.7, 97.1, 60.9, 100, 97.8, 92.8, 96.7, 98.6, 85, 100, 83.3, 100, 88. The total percentage of resistance rates frequency appears as follows: From 80–100 = 77.78%, from 50–70 = 20.99%, < 50 = 1.23%.
Meropenem
2007–2012:0.53.3, 86, 20, 100, 100, 94, 78.29, 100, 72, 92, 100, 91, 75, 73, 45, 71, 75, 88, 77, 86.6, 76.3, 100, 93.5, 92.7, 94, 100, 73.5, 98, 94.4, 98.9, 92, 100, 83.3, 78.6, 100, 58.3, 58.3, 71.4, 81.5, 100.
2012–2016: 100, 100, 91.6, 82.3, 93.94, 90.3, 89.8, 94.9, 73.8, 100, 86.9, 100, 94.3, 98.5, 96, 100, 98, 97.7, 94.2, 100, 95, 100, 100, 100.
2016–2021: 81.5, 72.8, 96, 95.2, 96.1, 81.7, 72.7, 97.1, 92.9, 100, 97.8, 93.1, 96.9, 95.9, 97.5, 100, 83.3, 100, 88.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 78.32%, from 50–70 = 19.28%, < 50 = 2.40%.
Ertapenem
2007–2012: no data found.
2012–2017: 99.6, 97.8.
2017–2021: no data found.
Doripenem
2007–2012: 100.
2012–2021: no data found.
Cephalosporins
(First generation) Cephalothin and (second generation) Cefuroxime were mentioned in 1 article for each of them, and third-generation Cephalosporins were found as follows: Cefixime in one article, Cefoperazone–sulbactam in 34 article, Cefotaxime in 14 articles, Ceftazidime in 61 article, Ceftriaxone in 15 article and (fourth generation) Cefepime was mentioned in 46 articles. All these antibiotics of this group used in studies were included in the research during the period from 2006 to 2021. Resistance rate percentages of A. baumannii against Cephalosporins were as follows:
Cephalothin
Two articles: One is performed in 2008 and the other from 2015–2017, and the two articles referred to 100% as a resistance rate.
Cefuroxime
Only one study was found performed between 2008 and 2012 and indicated 97.3% as a resistance rate against this antibiotic.
Cefoperazone–sulbactam
2007–2012: 63.9, 65, 26.7, 57, 36.6, 0, 87, 89, 79, 100, 92, 73.5, 73.6, 94.2, 77, 88.8, 45.7, 88.4, 78, 90.3, 89, 100, 21, 0, 9.1, 16.7.
2012–2016: 100, 98.15, 79.3, 77.8, 93.94, 79, 69.5, 93.6, 100, 98.3, 96.2, 69, 91.
2016–2021: no data found.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 46.16%, from 50–70 = 33.33%, < 50 = 20.51%.
Ceftazidime
2007–2012: 100, 86.7, 94, 86.6, 100, 97, 80.78, 100, 94, 95, 93, 100, 76.2, 96.1, 84, 98.9, 100, 97.8, 97.9, 98.9, 94.5, 100, 89.4, 100, 92.3, 91.4, 96.3, 100.
2012–2016: 100, 100, 86.6, 89, 100, 93.4, 86.7, 96.97, 96.8, 94.9, 88.6, 78.7, 100, 94.3, 99, 98.51, 100, 98.3, 98.9, 99.4, 100, 95, 98.5, 100, 100.
2016–2021: 80.5, 71.2, 98, 96.7, 95.3, 81.6, 75, 97.1, 100, 94.2, 98.6, 95, 100, 83.3, 100.
The total percentage of resistance rates appears as follows: From 80–100 = 94.12%, from 50–70 = 5.88%, < 50 = 0%.
Ceftriaxone
2007–2012: 100, 97, 100, 100, 100, 23.9.
2012–2016: 100, 85.4, 100, 100, 100.
2016–2021: 72.8, 96.5, 100.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 85.72%, from 50–70 = 7.14%, < 50 = 7.14%
Cefotaxime
2007–2012: 3.55, 97, 96, 100, 85, 98, 100, 98, 97.8, 100, 100, 100, 100.
2012–2016: 84.1, 78, 56, 98.9, 92.7, 100.
2016–2021: no data found.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 89.48%, from 50–70 = 5.26%, < 50 = 5.26%.
Cefixime
Only one study was found performed between 2011 and 2012 and indicated 81.13% as a resistance rate against this antibiotic.
Cefepime
2007–2012: 92, 100, 100, 97, 100, 95, 100, 95, 86, 94.8, 97.2, 95.3, 78, 100, 97.6, 100, 100, 96.8, 89.5, 100, 67.8, 100, 61.5, 80, 100, 100.
2012–2016: 82.9, 98, 100, 91.1, 82.2, 96.97, 93.7, 94.7, 32.8, 100, 96, 97.03, 100, 98.3, 99, 100, 100, 93. 2016–2021: 74.6, 97.5, 95.6, 72.7, 95.7, 100, 95.1. The total percentage of resistance rates frequency appears as follows: From 80–100 = 88.24%, from 50–70 = 9.80%, < 50 = 1.96%.
Monobactams
Aztreonam was the antibiotics of this group and mentioned in 5 articles: 2007–2012: 100, 100, 91.7. 2012–2016: 62.9, 63, 99.8. 2016–2021: 100. The total percentage of resistance rates frequency appears as follows: From 80–100 = 71.43%, from 50–70 = 28.57%, < 50 = 0%.
Penicillins
Antibiotics of this group found in research were Amoxicillin/clavulanate and Ampicillin found in 5 articles, Ampicillin/sulbactam in 42 articles, Piperacillin in 20 articles, Piperacillin/tazobactam in 59 articles, Ticarcillin and Ticarcillin/clavulanate found in 2 and 6 articles, respectively.
Amoxicillin/clavulanate
2007–2012: 100, 96.8, 70.3, 15.2.
2012–2017: 100.
2017–2021: no data found.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 60%, from 50–70 = 20%, < 50 = 20%.
Ampicillin
2007–2012: 100, 100, 100, 61.8.
2012–2017: 99.5.
2017–2021: no data found.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 80%, from 50–70 = 20%, < 50 = 0%.
Ampicillin/sulbactam
2007–2012: 40, 100, 53.3, 100, 97, 97.35, 100, 100, 82, 72.5, 96.8, 95.7, 97.9, 90.6, 93.5, 87.5, 11.9.
2012–2016: 100, 76.8, 100, 91.4, 88.9, 91.7, 69.6, 13.1, 100, 96.1, 94.07, 94, 98.3, 98.6, 100, 99.4, 100, 74, 100, 100, 100.
2016–2021: 62.8, 86.1, 94.5, 72.7, 95.7, 87.5, 100, 66.6, 100.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 80.86%, from 50–70 = 12.76%, < 50 = 6.38%.
Piperacillin
2007–2012: 100, 100, 97, 90.03, 100, 99, 100, 69.2, 100, 100, 100, 100, 100.
2012–2016: 100, 84.1, 100, 97.4, 99.5, 100, 89.
2016–2021: 99.6, 96.2.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 95.46%, from 50–70 = 4.54%, < 50 = 0%.
Piperacillin/tazobactam
2007–2012:100, 93.3, 94, 80, 0, 97, 96, 84, 97, 81.1, 90, 97.2, 96, 96, 100, 91.7, 100, 98.1, 98.9, 96, 48.6, 99, 95.5, 100, 85.7.
2012–2016: 100, 100, 81.7, 78, 100, 93.2, 82.2, 96.97, 92.8, 97.5, 75.4, 100, 92.6, 95, 97.7, 92, 100, 98.6, 98.1, 94.2, 100, 100, 93, 100, 100.
2016–2021: 82, 74, 99, 97.6, 98.9, 83.5, 72.7, 97.1, 95.7, 100, 91.6, 98.6.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 91.94%, from 50–70 = 4.84%, < 50 = 3.22%.
Ticarcillin
2007–2012: 100, 100.
2012–2021: no data found.
Ticarcillin/clavulanate
2007–2012: 97.9, 100, 97.1, 98.5.
2012–2018: 99.3, 97.5
2018–2021: No data found.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 100%, from 50–70 = 0%, < 50 = 0%.
Quinolones/fluoroquinolones
Antibiotics of this group found in research were Ciprofloxacin found in 68 articles, Levofloxacin in 33 articles, Ofloxacin and moxifloxacin which are found in one article for each of them.
Ciprofloxacin
2007–2012: 100, 99, 53.3, 81, 94, 87.5, 92, 76, 100, 92, 86.8, 81.1, 86, 95, 98.2, 95.7, 85, 100, 98, 100, 96.2, 97.8, 97, 100, 100, 82.9, 99, 90.47, 92.3, 91.4, 96.3, 100.
2012–2016: 100, 100, 84.1, 98, 100, 93.2, 83, 97.3, 91.7, 96.2, 77, 100, 93.4, 95, 98.51, 94, 100, 97.7, 98.8, 100, 100, 100, 100, 100, 97.7, 100, 100.
2016–2021: 81, 73.7, 97, 95.6, 94.3, 80.5, 72.7, 97.1, 100, 95.7, 93.4, 96.6, 98.6, 95, 100, 100, 92.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 93.42%, from 50–70 = 6.58%, < 50 = 0%.
Levofloxacin
2007–2012: 60, 89, 69.7, 100, 73, 94, 95.5, 81.1, 90, 100, 90.3, 95.8, 71.4.
2012–2016: 90.9, 82.2, 95.3, 89.5, 86, 74.6, 100, 97.77, 100, 97.7, 97.5, 96.9, 82, 93, 100.
2016–2021: 93, 95.5, 97.1, 60.1, 100, 91.6, 91.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 82.85%, from 50–70 = 17.15%, < 50 = 0%.
Ofloxacin
Only one study was found performed between 2007 and 2008 and indicated 98% as a resistance rate against this antibiotic.
Moxifloxacin
Only one study was found performed between 2009 and 2010 and indicated 22.62% as a resistance rate against this antibiotic.
Sulfonamides
Trimethoprim–Sulfamethoxazole was the only antibiotic used from this group and was mentioned in 50 articles.
2007–2012: 93.3, 59, 69, 81.13, 100, 83, 64.9, 63.7, 91.9, 91, 91.7, 85.4, 73.6, 72, 67.5, 77.5, 73, 92.3, 85.7, 96.3, 71.3.
2012–2016: 100, 95, 50, 89, 77.8, 68.9, 81.2, 91.1, 72.1, 96, 100, 88.3, 80.6, 76.8, 53, 96, 73.3, 100, 79.3.
2016–2021: 61.9, 73.9, 68.9, 59, 81.8, 82.3, 100, 58.7, 75.6, 85.7, 93.2, 90, 83.8, 50, 93.8, 63.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 53.57%, from 50–70 = 46.43%, < 50 = 0%.
Tetracyclines
This group included Doxycycline, Minocycline and Tetracycline. Doxycycline and Minocycline are mentioned in 2 articles, while Tetracycline in 17 articles.
Doxycycline
Two articles were performed in 2015 and 2018 and referred to 100% and 91.2%, respectively, as a resistance rate.
Minocycline
Two articles were performed in 2015 and 2018 and referred to 100% and 76.5%, respectively, as a resistance rate.
Tetracycline
2007–2012: 100, 70, 70.46, 55, 78, 87.8, 66.3, 72.
2012–2016: 94, 19.5, 97.7, 77.2, 76.4, 100, 93.7, 86.4, 83.
2016–2021: no data found.
The total percentage of resistance rates frequency appears as follows: From 80–100 = 47.05%, from 50–70 = 47.05%, < 50 = 5.90%.
Polypeptides
Colistin was tested in 72 articles, while Polymyxin B in one article.
Polymyxin B
One article was conducted between 2009 and 2011, and the resistance rate was 0%.
Colistin
2007–2012: 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 14, 0, 0, 0, 0, 2.9, 6, 0, 0, 0, 0, 0.6, 0, 0, 0, 0,
2012–2016: 0, 0, 0, 1.4, 0.29, 0, 5.5, 0.8, 0, 5.1, 0, 0, 3.5, 0, 0, 0, 0, 100, 0, 0, 2.1, 0.3, 2.9, 0, 1.2, 0, 0, 0, 0, 100
2016–2021: 6.8, 28, 0.5, 2.5, 3, 1.8, 13.6, 17.6, 0, 12.5, 2.2, 12.8, 9.1, 1.4, 0, 10.5, 0, 9.2.
The total percentage of resistance rates frequency appears as follows: 0 = 58.66%, from 0–10 = 29.33%, from 10–20 = 8%, from 20–30 = 1.33%, from 30–90 = 0%, 100 = 2.66%.
Tigecycline
This antibiotic found to be tested in 54 articles.
2007–2012: 0, 0, 0, 29, 0, 0, 11, 0, 6.6, 0, 37.7, 25, 44.9, 12.5, 34.8, 81.3, 23, 1, 2, 5.7, 2.7, 0.
2012–2016: 0, 40.8, 6.9, 72.4, 18.2, 41.3, 5.1, 3.8, 64, 6.1, 88.9, 66.7, 10.37, 0, 26.6, 49.3, 0, 1.7, 45.8, 2, 9.3, 11.4.
2016–2021: 30, 11, 21.7, 22, 58.8, 73.9, 18.7, 5.9, 6.8, 10. The total percentage of resistance rates frequency appears as follows: 0 = 20.37%, from 0–10 = 27.77%, from 10–20 = 11.11%, from 20–40 = 14.81%, from 40–80 = 16.66%, from 80–100 = 3.70%.
Sulbactam
This antibiotic was mentioned in 5 articles.
2007–2012: 26.6, 8
2012–2016: 100, 100
2018–2021: 73.9
The total percentage of resistance rates frequency appears as follows: From 80–100 = 40%, from 50–70 = 20%, < 50 = 40%.
Others
Chloramphenicol
One article was conducted between 2006 and 2010 and referred to 100% as a resistance rate.
Fosfomycin
Two articles were conducted between 2008–2012 and 2012–2017 and referred to 48.6% and 100%, respectively, as a resistance rate.
Nitrofurans
Nitrofurantoin was the antibiotics of this group and mentioned in two articles conducted between 2012–2014 and 2015–2017 and referred to 99.1% and 97.8%, respectively, as a resistance rate.
Rifampicin
Two articles were conducted between 2009–2011 and 2009–2010 and referred to 35% and 47.62%, respectively, as a resistance rate.
Based on all previous results, we found that 15 antibiotics were tested continuously at high frequency over the study years.
Trends in antibiotic resistance that occurred most frequently over the years were represented by a graph in Fig. 1. The overall percentages of a resistance rate for these antibiotics used between 2007 and 2021 were also represented by a graph in Fig. 2.
Most frequent antibiotics with percentages that have shown resistance rate (80–100%) over the years (A). Trends of percentages of Colistin and Tigecycline sensitivity rates over the years (B)
The total percentages of resistance rates for the most widely used antibiotics from 2007 to 2021 (A). Total percentages of Colistin and Tigecycline from 2007 to 2021 based on their sensitivity rates (B)
Groups: 6 articles used the group of antibiotic to indicate the resistance rate.
Aminoglycosides
2012 (33), 2014–2015 (70.9).
b-lactams
2012 (100).
Carbapenems
2007–2010 (92), 2013–2014 (100), 2014–2015 (100), 2014–2015 (91.8), 2014–2018 (75).
Cephalosporins
2014–2015 (93.8), 2014–2018 (100).
Quinolones
2007–2010 (88), 2014–2015 (98), 2014–2018 (100).
Conclusions
Emerging of highly resistant A. baumannii to most available antimicrobial agents led to a high incidence of morbidity and fatality mostly for intensive care units patients (Vrancianu et al. 2020; Lee et al. 2022). A 9-year research conducted in a university hospital in Turkey revealed that 81.9% of pathogens detected in clinical specimens were Gram-negative bacteria and A. baumannii constituted 34.8% and was the most frequent bacteria in patients with pneumonia, catheter infections, sepsis, wound infections and meningitides. The same study found that A. baumannii was the most common bacteria in intensive care units with a rate of 34.8% (Yetkin et al. 2018). In our study, we found that A. baumannii was isolated from intensive care units patients in 72.5% of the articles. Our study also revealed that about 40 antibiotics were tested against A. baumannii from 2006 to 2021 with a different frequency and these antibiotics were Amikacin, Gentamicin, Netilmicin, Tobramycin, Doripenem, Ertapenem, Imipenem, Meropenem, Cephalothin, Cefuroxime, Cefixime, Cefoperazone–sulbactam, Cefotaxime, Ceftazidime, Ceftriaxone, Cefepime, Aztreonam, Amoxicillin/clavulanate, Ampicillin, Ampicillin/sulbactam, Piperacillin, Piperacillin/tazobactam, Ticarcillin, Ticarcillin/clavulanate, Ciprofloxacin, Levofloxacin, Ofloxacin, moxifloxacin, Trimethoprim–Sulfamethoxazole, Doxycycline, Minocycline, Tetracycline, Colistin, Polymyxin B, Tigecycline, Sulbactam, Chloramphenicol, Fosfomycin, Nitrofurantoin and Rifampicin. But the frequent antibiotics that constitute the clear map of antibiotics used by health institutions in Turkey against A. baumannii for the last 10 years were Amikacin, Gentamicin, Imipenem, Meropenem, Cefoperazone–sulbactam, Ceftazidime, Cefepime, Ampicillin/sulbactam, Piperacillin, Piperacillin/tazobactam, Ciprofloxacin, Levofloxacin, Trimethoprim–Sulfamethoxazole, Colistin and Tigecycline. These 15 antibiotics were tested continuously with a large frequency during the last years against A. baumannii. The results referred to the stability for years of the high resistance rates against some antibiotics and increase in the resistance rates against other antibiotics. We found, for example, that highly resistance rates of A. baumannii against Imipenem, Meropenem, Cefoperazone–sulbactam, Ceftazidime, Cefepime, Ampicillin/sulbactam, Ciprofloxacin were steadily stable for the last 10 years. This result goes with data surveillance report published by World Health Organization (WHO) which included the antimicrobial resistance surveillance in Europe 2020–2022. The report showed that resistance phenotype (%) by Acinetobacter spp. against Carbapenem (Imipenem/Meropenem) in Turkey from 2016–2020 was as follows: 2016 (91.6), 2017 (91.5%), 2018 (92.2%), 2019 (90.4%) and 2020 (93.1%) and for Fluoroquinolone (Ciprofloxacin/Levofloxacin) as follows: 2016 (92.1%), 2017 (92.6%), 2018 (94.4%) 2019 (90.7%) and 2020 (93.6%) (European Centre for Disease Prevention and Control World Health Organization. Regional Office for Europe. Antimicrobial resistance surveillance in Europe 2022–2020 data 2022). Similar findings for Imipenem, Meropenem, Ampicillin/sulbactam and Ciprofloxacin have been reported in a very recent article (Çiftçi et al. 2022). The analysis in our study showed clearly that the increase in resistance rate against Colistin and Tigecycline was in ascending pattern for the last 5 years especially for Colistin which is considered as the last option for treatment. This result is compatible with analysis study on Colistin resistance in A. baumannii species in Turkey. The study which included 44 articles found a partial decrease in Colistin sensitivity in some regions over the years and more decrease in others. The study reported İzmir, Samsun, Diyarbakır, Düzce and Ankara as cities with the lowest Colistin susceptibility with rates of 81.8%, 82.4%, 94%, 94.1% and 95.8%, respectively. The study concluded that resistance development against Colistin has increased over the years (Görgün et al. 2021). According to the recent report by World Health Organization, the number of isolates of Acinetobacter spp. reported by laboratories in Turkey was increased from 2.463 isolates in 2016 to 3.170 in 2020. The report also indicated that percentage of isolates was higher in males and in age group 65 and over in year 2020 (European Centre for Disease Prevention and Control World Health Organization. Regional Office for Europe. Antimicrobial resistance surveillance in Europe 2022–2020 data 2022).
The continuous increase in A. baumannii numbers in health institutions especially in intensive care units with the high mortality caused by this pathogen needs huge studies and to be more highlighted. So we introduced in this study a detailed analysis about the picture of antibiotics profile that is used and tested against A. baumannii by different health institutions from different cities of Turkey from 2006 to 2021. We believe that the detailed numbers in our study can give a clear map about the types of antibiotics used continuously and the susceptibility profile regarding these antibiotics for the last 10 years. All the information in this study can be used by all health associations of Turkey including state hospitals and clinics and academic teaching hospitals to re-evaluate all the antibiotics used against A. baumannii. Although treatment options still very limited for A. baumannii, the reevaluation can answer the question about the reasonability of using the antibiotics that gave stability in high resistant rates for five years or even more. A study included four university hospitals and one state hospital in Ankara and concluded that the reduced consumption of Carbapenems was associated with decreased Carbapenems-resistant by Acinetobacter spp. and Pseudomonas spp. (Altunsoy et al. 2011). According to our results, we believe that the evaluation can also clarify that the continuous using of effective antibiotics as Colistin and Tigecycline can lead to decrease in Colistin sensitivity in few years. Therefore, reconsideration of antibiotic policies by the health institutions as well as the wise application of antibiotics in the future against A. baumannii is highly recommended. Precise and detailed studies regarding antibiotics used by every health setting against A. baumannii must be reported annually because of the rapid development in resistance by this pathogen. Long studies without annual numbers and mixed studies from different clinics or from different cities are not recommended because these studies may not give the real numbers about resistance phenotype by A. baumannii against antibiotics. For example, during analyzing the articles we found that a multicenter study that depended on collection of A. baumannii strains from hospitals located at 12 different provinces of Turkey reported a lower resistant rates against some antibiotics (Beriş et al. 2016). Therefore, we suggest that sensitivity test for A. baumannii strains must perform by the same clinic and in the same region of isolation. Recent study found that positive blood cultures were linked with increased odds of 90-day mortality comparing to urine cultures in patients with Carbapenem-resistant Acinetobacter baumannii (CRAB) and Carbapenem-resistant Pseudomonas aeruginosa (CRPA) (Vivo et al. 2022). Related findings were noticed during analysis of articles in our study, since we found that A. baumannii strains isolated from specific specimens gave a high resistance rate against some antibiotics. For example, in two studies a high resistance rate by A. baumannii strains most isolated from blood samples against Colistin and Tigecycline was reported with percentage of 14% for Colistin and 40.8 for Tigecycline (Bozkurt-Guzel et al. 2014; Karagöz et al. 2014). On the contrary, a different study reported a low resistance rate with (14.5%) against Tetracycline by A. baumannii strains isolated from blood. Another article in our study referred to clear difference in resistance rate against Colistin by A. baumannii strains isolated from sputum which gave 0% resistance rate and A. baumannii strains isolated from deep tracheal aspirate which gave 10.5%.resistance rate (Şenol et al. 2022). All these results may highlight the value of further studies to be performed regarding the relationship between the susceptibility of A. baumannii against antibiotics and the type of specimen that A. baumannii isolated from. More information in that field would improve treatment of patients infected with this pathogen in a timely manner. Combination therapy should take more attention in future studies. The use of at a minimum two active agents if possible is recommend according to the guidelines for treatment of Carbapenem-resistant Acinetobacter baumannii released by Infectious Disease Society of America (IDSA). The (IDSA) described the therapy of Ampicillin-sulbactam (high dose when the causative agent is indicated as resistant) combined with either Tigecycline or Minocycline as preferred choice (Tamma et al. 2022). Taking in consideration all the above issues in addition to obligatory infection control actions providing sufficient area and developing systems in intensive care units can support the aims in combating A. baumannii in hospitals. Therefore, efforts by all medical institutions related to critical care must be more activated and effective procedures to fight these organisms that cause high mortality should become a priority.
This study can assist in giving a precise image about antibiotics profiles used within the last years. As well, we believe that findings in our research are corresponding to the nationwide antibiotic restriction program (NARP) which is released in Turkey in 2003 and proved its effectiveness in reducing the costs and antibiotic resistance which is the same goal that we seek through work in this study. Our results may promote the development of alternative antimicrobial regimens for treatment of A. baumannii and may improve antibiotics regimens to be applied in the future. Further surveillance and studies on the development and epidemiological characteristic of clinical A. baumannii strains are required.
Availability of data and materials
Not applicable.
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Abed, A.B., Korcan, S.E. & Güngör, S. Antibiotics profile map of clinical A. baumannii strains isolated from health institutions in Turkey: a database search study and analysis of publications from 2011 to 2022. Bull Natl Res Cent 47, 15 (2023). https://doi.org/10.1186/s42269-023-00982-6
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DOI: https://doi.org/10.1186/s42269-023-00982-6