|Year : 2022 | Volume
| Issue : 4 | Page : 369-374
Microbiota of dental abscess and their susceptibility to empirical antibiotic therapy
M Jemima Judith1, Nalini Aswath1, Kesavaram Padmavathy2
1 Department of Oral Medicine and Radiology, Sree Balaji Dental College and Hospital, BIHER, Chennai, Tamil Nadu, India
2 Department of Microbiology, Research Laboratory for Oral Systemic Health, Sree Balaji Dental College and Hospital, BIHER, Chennai, Tamil Nadu, India
|Date of Submission||22-Dec-2021|
|Date of Decision||05-Jan-2022|
|Date of Acceptance||05-Jan-2022|
|Date of Web Publication||03-Nov-2022|
Dr. Nalini Aswath
Department of Oral Medicine and Radiology, Sree Balaji Dental College and Hospital, BIHER, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Context: Resistant pathogens to purulent odontogenic infections have evolved due to misuse of antibiotics. Hence, it is important to use a suitable antibacterial agent. Aim: This study aimed to identify the common bacterial species causing odontogenic infections and to determine their antibiotic susceptibility profile to amoxicillin, amoxicillin and clavulanic acid, azithromycin, and linezolid. Settings and Design: This was an in vitro cross-sectional study. Material and Methods: Fifty pus samples from odontogenic abscess were cultured and antibiotic susceptibility tests were performed as per the standard microbiological procedures. Statistical Analysis Used: Binomial test and Pearson's Chi-square test were used for statistical analysis. Results: Out of the 50 samples cultured, 30 samples showed growth. The distribution of growth among the 30 samples was Gram-positive cocci (n = 23, 67.65%) and Gram-negative bacilli (n = 11, 32.35%). Gram-positive isolates that were grown were Enterococcus faecalis (38.24%) followed by Staphylococcus aureus (29.41%) and Gram-negative bacilli that were isolated were Klebsiella pneumoniae (14.71%), Pseudomonas aeruginosa (8.82%), Escherichia coli (5.88%), and Enterobacter (2.94%). Enterococcus isolates were highly susceptible to amoxicillin (76.92%). An increase in the zone of inhibition to amoxicillin–clavulanic acid was appreciated more for Staphylococcus (50%) than Enterococcus (30.76%). Enterococcus and Staphylococcus showed high susceptibility of 92.31% and 90% to linezolid, respectively. E. coli and Enterobacter were 100% susceptible to amoxicillin. All the Gram-negative bacteria except for P. aeruginosa were 100% highly susceptible to amoxicillin–clavulanic acid. Conclusions: Culture-guided antibiotic prescriptions are necessary to prevent the emergence of antibiotic-resistant bacteria.
Keywords: Antibiotic sensitivity, culture, dental abscess, disk-diffusion method
|How to cite this article:|
Judith M J, Aswath N, Padmavathy K. Microbiota of dental abscess and their susceptibility to empirical antibiotic therapy. Contemp Clin Dent 2022;13:369-74
| Introduction|| |
Dental abscesses are polymicrobial infections, consisting of aerobes, facultative and obligate anaerobes. In recent times, drug resistance of genetic and acquired nature among the aerobes and facultative anaerobes is increasing due to indiscriminate use of over-the-counter drugs, thereby making treatment difficult. Studies have shown that isolated bacterial pathogens showed resistance to commonly prescribed drugs such as ampicillin, amoxicillin + clavulanic acid. Hence antibiotic therapy with culture-guided prescriptions is necessary. Due to the questionable response of the pathogens to the empirical drugs due to the increase in the incidence of resistance, antibiotic therapy without culture-guided prescriptions may or may not produce good outcomes which might lead to life-threatening situations in certain instances. For a clinician considering antibiotic therapy, data on bacterial etiology and pathogen susceptibility are important. Acquiring such information, though, may take several days or even longer. Recent data on microbiota for purulent odontogenic infections are lacking despite the high frequency of clinical cases. A rational approach to empirical antibiotic selection based on scientifically sound and current experience with the continuously evolving flora of orofacial infections is required. Thus, this study aims to identify the bacterial profile of odontogenic infections (mostly facultative anaerobes and aerobes) and to screen for their respective antibiotic susceptibility profile, as an initiative to avoid the emergence of antibiotic resistance and also to identify the suitable antibiotic for the management of odontogenic infections.
[TAG:2]Material and Methods[/TAG:2]
This is a prospective, cross-sectional in vitro study performed on fifty pus samples collected from 50 patients with odontogenic abscess (26 males [52%] and 24 females [48%]) aged between 5 and 75 years. Through a literature survey and pilot study, it was observed that nearly 3% of patients had purulent discharge from odontogenic infections. Assuming the margin of error as 5%, with an α level of 0.05, the sample size was calculated using the formula:
n = p × q × (1.96 ÷ d)2 where P = 0.03, q = 1 – P = 0.97; d = 0.05 and Zα = 1.96
(Zα is standard normal value with 95% confidence interval for α = 0.05)
Thus, the minimum sample size required was 45. Considering 10% attrition rate, 50 samples were selected using a systematic random sampling method over a period of 4 months. In this prospective study, patients with pus discharge from various odontogenic infections such as periapical abscess (n = 26), periodontal abscess (n = 20), and pericoronal abscess (n = 4) were enrolled from the outpatient department of oral medicine and radiology with appropriate consent. Patients who were on antibiotic therapy either at the time of the study (or) in the recent past were excluded from the study. The study protocol was approved by the Institutional Ethics Committee (SBDCH/IEC/04/2019/4, dt. 05/06/2019). The study followed all principles of the Helsinki Declaration 2013. Written informed consent was obtained from all the study subjects before sample collection. Sample collection was done intraorally by isolating the area of the swelling in relation to the offending tooth by cotton rolls and suction for periapical and periodontal abscess. For pericoronal infections, the plaque was removed from the partially erupted tooth by cotton swabs and it was isolated accordingly. In periapical abscess, the corresponding X-rays showed ill-defined radiolucency in the apex of the offending tooth. For periodontal abscess, there was bone loss found with radiolucency around the tooth root in the corresponding X-rays. Then, the pus was aspirated using a sterile syringe/collected using two sterile cotton swabs from the pyogenic orifice. It was transported immediately to the microbiology laboratory in a sealed sterile container and was processed as per the standard microbiological procedures.
One cotton swab was used for Gram staining and the other swab was used for bacterial culture. Pus samples were inoculated on sterile blood agar (5% sheep blood) and MacConkey agar plates. The inoculated blood agar plates were incubated in a candle jar and the MacConkey agar plates were incubated aerobically at 37°C overnight in the bacteriological incubator and examined for bacterial growth. Then, the bacteria were identified to the genus level. After identification, antibiotic susceptibility testing was performed using the Kirby–Bauer Disk diffusion method as per the Clinical and Laboratory Standards Institute (CLSI) guidelines, 2019. Briefly, lawn culture of the test organism was made on separate Muller–Hinton agar plate using ethylene oxide-sterilized cotton swabs (HiMedia Laboratories Pvt Ltd., Mumbai, India). Then, the antibiotic disks, amoxicillin (20 μg), amoxicillin–clavulanic acid (20/10 μg), linezolid (30 μg), and azithromycin (15 μg) were placed and the plates were incubated aerobically at 37°C overnight. The diameter of the zones of inhibition around the antibiotic disks was measured and recorded. Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Enterococcus faecalis ATCC 29212 were used as Quality control strains.
A Microsoft Excel spreadsheet was used for data entry such as sample number, age, gender, presence of growth, species, and antibiotic sensitivity to amoxicillin, amoxicillin plus clavulanic acid, azithromycin, and linezolid. Statistical calculation was performed on IBM SPSS software (Version 24) (Armonk, NY: IBM Corp, Released 2016). Bacterial profile in each type of abscess, sensitivity of Gram-positive Cocci, and Gram-negative bacilli to empirical antibiotic therapy were evaluated using the binomial test and Pearson's Chi-square test.
| Results|| |
Among the 50 samples, 30 samples belonging to 18 males and 12 females showed growth. Among the 30 samples, 17 (56.67%) were periapical abscess, 10 (33.33%) were periodontal abscess, and 3 (10%) were pericoronal abscess. Thirty-four isolates of bacterial pathogens were obtained from the 30 samples. Twenty-six had monoculture (1 isolate per sample) and 4 had mixed bacterial growth (2 isolates per sample). Among the 34 bacterial isolates, Gram-positive cocci (67.65%) were the most frequently isolated organism than Gram-negative bacilli (32.35%) [Figure 1]. The growth observed was predominantly of Gram-positive cocci such as E. faecalis (38.24%) followed by S. aureus (29.41%) and Gram-negative bacilli such as Klebsiella pneumoniae (14.71%), Pseudomonas aeruginosa (8.82%), E. coli (5.88%), and Enterobacter (2.94%) [Figure 1]. Among the 17 samples from periapical abscess, 7 (35%) E. faecalis, 7 (35%) S. aureus, 2 (10%) K. pneumoniae, 2 (10%) P. aeruginosa, 1 (5%) E. coli and 1 (5%) Enterobacter were isolated. Aerobes and facultative anaerobes were more frequently isolated in periapical abscess than any other dental abscesses. Among the 10 samples from periodontal abscess, 6 (54.55%) E. faecalis, 2 (18.18%) S. aureus, 2 (18.8%) K. pneumoniae, and 1 (9.09%) P. aeruginosa were isolated. Among the three samples from pericoronal abscess,
1 (33.33%) S. aureus, 1 (33.33%) K. pneumoniae, and 1 (33.33%) E. coli were isolated. S. aureus and Klebsiella Pneumonia were the most frequent facultative anaerobes found among all types of abscess [Figure 2]. The predominant isolates from various samples were tested for antibiotic susceptibility. The same type of species isolated from various samples yielded different antibiotic susceptibility results. Among the 13 E. faecalis isolates, majority of the isolates 12/13 (92.31%) were susceptible to linezolid (P = 0.003) compared to amoxicillin 10/13 (76.92%) (P = 0.092) and azithromycin 6/13 (46.2%). According to this study, linezolid would be an effective antibiotic in the treatment of dental abscess caused by Enterococci [Table 1]. Among the 10 S. aureus isolates, one isolate was found to be resistant to all the antibiotics tested. Majority of the Staphylococcus isolates 9/10 (90%) (P = 0.021) were susceptible to linezolid compared to amoxicillin 8/10 (80%) (P = 0.109) and azithromycin 5/10 (50%) [Table 2]. Since no interpretation criteria by CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines are available for amoxicillin–clavulanic acid for Staphylococcus and Enterococcus by disk-diffusion method, no interpretations were recorded. However, on the addition of clavulanic acid to amoxicillin, increased zone of inhibition was seen in 4/13 (30.76%) of the Enterococci isolates and 5/10 (50%) of the Staphylococcus isolates. Antibiotic sensitivities for E. faecalis and S. aureus to empirical antibiotic therapy are tabulated in [Table 1] and [Table 2]. Among the Gram-negative bacilli isolates (Enterobacteriaceae), all the K. pneumoniae isolates were 100% resistant to amoxicillin compared to E. coli and Enterobacter which were 100% susceptible to amoxicillin [Table 3]. All the K. pneumoniae isolates were β-lactamase producers, which were judged by the increment in the zone of inhibition when clavulanate was combined with amoxicillin. Therefore, amoxicillin–clavulanic acid would be effective against β-lactamase producing Klebsiella species according to this study. Since no zone of inhibition was observed in all P. aeruginosa isolates to amoxicillin, it was considered to be 100% resistant. 1/3 (33.33%) isolate showed intermediate sensitivity to amoxicillin and clavulanic acid and 2/3 (66.67%) were resistant to amoxicillin and clavulanic acid (P = 1.000) [Table 4]. Antibiotic susceptibility patterns of the K. pneumoniae, E. coli, Enterobacter, and P. aeruginosa to empirical antibiotic therapy are tabulated in [Table 3] and [Table 4].
|Table 1: Sensitivity of Gram-positive bacteria - Enterococcus faecalis - to empirical antibiotic therapy|
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|Table 2: Sensitivity of Gram-positive bacteria-Staphylococcus aureus to empirical antibiotic therapy|
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|Table 3: Sensitivity of Gram-negative bacteria - Klebsiella pneumoniae, Escherichia coli, and Enterobacter - to empirical antibiotic therapy|
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|Table 4: Sensitivity of Gram-negative bacteria - Pseudomonas aeruginosa - to empirical antibiotic therapy|
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| Discussion|| |
Despite the increased incidence of odontogenic infections, there is a paucity of data on the bacteriological profile and the antimicrobial resistance pattern of the isolates. Such data are a prerequisite for the development of clinical recommendations and guidelines on the antibiotic prescribing practices to be adopted by dentists for the therapeutic management of odontogenic infections. In this study, the specimens were analyzed for facultative anaerobes and aerobes. This was done to elicit if there was any variation from the species reported in the previous studies. Among the isolated pathogens, Gram-positive bacteria dominate the Gram-negative bacteria in the present study [Figure 1] which is consistent with the previous report by Brescó-Salinas et al. in 2006. In this study, E. faecalis was the most predominant organism isolated which is similar to the study by Brescó-Salinas et al. in 2006 where E. faecalis and Streptococcus species were the predominant facultative anaerobes isolated. In the present study, the species differed slightly among all the type of abscesses and also aerobes and facultative aerobes were more frequently isolated in periapical abscesses. These results were similar to the study by Kuriyama et al. in 2000. Periapical abscess was the most common abscess in this study. This is similar to the study done by Kuriyama et al. in 2000 where the periapical abscess was 78%, then periodontal abscess 15% and pericoronal abscess 11%. In the present study, the predominant organisms isolated from periapical abscess were both E. faecalis (35%) and S. aureus (35%) [Figure 2]. This is in accordance to the study done by Brescó-Salinas et al. in 2006 where E. faecalis (19.2%) was the most predominant organism isolated from periapical infections among the facultative anaerobes.
Previous reports suggest that unnecessary antibiotic prescriptions significantly contribute to the development of antibiotic resistance. Furthermore, antibiotic prophylaxis (potential overuse of antibiotics) is hardly ever addressed in dentistry. Hence, periodic surveillance for antibiotic resistance, education on antibiotic stewardship, routine audit, and feedback could be an intervention in hospital dental care and outpatient dental settings. Brescó-Salinas et al. in 2006 had 91.4%, 34.2%, 91.4% of susceptibility of E. faecalis for amoxicillin, azithromycin, and linezolid, respectively, which is in accordance with this study [Table 1]. S. aureus was 37% sensitive to amoxicillin, according to Mahalle et al. in 2014, 76.95% were sensitive to Azithromycin, according to Jagadish Chandra et al. in 2017 and 60% sensitivity for linezolid, according to Jindal et al. 2019 respectively. These studies are in accordance to this study [Table 2]. K. pneumoniae was 36.4% sensitive to amoxicillin according to Shah et al. in 2016 and 31.25% sensitive to azithromycin according to Al-Mehedi et al. in 2015 which was contrary to the present study. It was 100% sensitive to amoxicillin clavulanate in the study conducted by Mahalle et al. in 2014 which is similar to the present study [Table 3]. For E. coli, according to Jagadish Chandra et al. in 2017, it is 100% sensitive to amoxicillin and according to Mahalle et al. in 2014, it is 100% sensitive to amoxicillin clavulanate. These studies are similar to this study. According to Al-Mehedi et al. in 2015, it is 0% sensitive to azithromycin. This study is contrary to the present study [Table 3]. For Enterobacter species, according to Abdulla et al. in 2009, it is 0% sensitive to amoxicillin, according to Prakash et al. in 2016, it is 0% sensitive to amoxicillin clavulanate. These studies are similar to this study. According to Jagadish Chandra et al. in 2017, it is 100% sensitive to azithromycin. This study is contrary to the present study [Table 3]. According to Shah et al. in 2016, the aerobe P. aeruginosa was 0% sensitive to amoxicillin which is similar to the present study and amoxicillin clavulanate was 0% sensitive which was contrary to the present study [Table 4]. Amoxicillin and amoxicillin–clavulanic acid are the empirical drugs used for facultative anaerobes and aerobes. Erythromycin or azithromycin are used when patients are allergic to the penicillin group of antibiotics.,, Metronidazole is excellent for acute infections and obligate anaerobes developing resistance against it are rare. Hence in the present study, only the facultative anaerobes and aerobes are isolated and screened for sensitivity to amoxicillin, amoxicillin–clavulanic acid, and azithromycin. Linezolid, an oxazolidinone, a recent reserve drug, is used against multidrug-resistant Gram-positive organisms. Hence, linezolid was also tested along with the commonly prescribed drugs. Linezolid is not recommended for Gram-negative bacteria and no interpretation criteria were provided by both CLSI and EUCAST guidelines. In case of E. coli and Enterobacter which were 100% susceptible to amoxicillin, prescribing amoxicillin and clavulanic acid is not required as they would result in the emergence of drug-resistant strains. Since piperacillin–tazobactam is a suitable drug for Pseudomonas species, culture and antibiotic susceptibility tests for piperacillin–tazobactam are required before prescribing the same. Recent reports showed that there is an emergence of beta-lactamase-producing K. pneumoniae which were similar to this study results. Teoh et al. in 2021 concluded in their systematic review of eight studies that there are no ideal antibiotic regimens for treating orofacial infections. They also stated that broad-spectrum antibiotics ought not to be prescribed as narrow-spectrum antibiotics also offer effective results for otherwise healthy people. Thus in concurrence with Teoh et al., the results of our study suggest that the antibiotic resistance pattern of the patient's dental microbiota needs to be evaluated for effective antibiotic therapy and to reduce the development of resistance. Antibiotic-resistant bacterial strains that are associated with dental and oral-maxillofacial infections are a significant cause of mortality and morbidity worldwide and are a cause of severe health concern.,, Hence, patient education and awareness about the proper use of antibiotics should be made known to the general public to avoid misuse of antibiotics such as over-the-counter drugs and self-medications.
Of the 50 samples, only 30 samples showed growth. This could be because of patients who did not reveal the intake of over-the-counter antibiotics before sample collection. Nonbeta-lactamase-producing Enterococci susceptible to ampicillin were predictively assumed to be susceptible to amoxicillin-clavulanate as CLSI does not give interpretative criteria for the same.
Future research directions
Continued research pertaining to orofacial infection of odontogenic origin with larger sample size is needed periodically as different bacterial strains emerge and the bacterial resistance to various antibiotics may vary from time to time. Advanced, rapid, feasible, cost-effective, less tedious, and less technique sensitive laboratory procedures to process and to identity the bacterial strains and their sensitivity to antibiotics are required to combat emerging resistant strains.
| Conclusions|| |
This study reveals that culture-guided antibiotic prescriptions are necessary to prevent the emergence of microbial resistance to antibiotics, thus preventing the spread of antibiotic-resistant bacterial species.
The authors would like to thank Tamil Nadu State Council for Science and Technology.
Financial support and sponsorship
This study was supported by a grant from Tamil Nadu State Council for Science and Technology.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Robertson D, Smith AJ. The microbiology of the acute dental abscess. J Med Microbiol 2009;58:155-62.
Ajantha G, Veda H. Antibacterial drug resistance and its impact on dentistry. NY State Dent J 2012;78:38-41.
Gaetti-Jardim EC, Marqueti AC, Faverani LP, Gaetti-Jardim E Jr. Antimicrobial resistance of aerobes and facultative anaerobes isolated from the oral cavity. J Appl Oral Sci 2010;18:551-9.
Hasan W, Leonard D, Russell J. Ludwig's angina – A controversial surgical emergency: How we do it. Int Journ Otolaryngol 2011;231816:1-4.
Chunduri NS, Madasu K, Goteki VR, Karpe T, Reddy H. Evaluation of bacterial spectrum of orofacial infections and their antibiotic susceptibility. Ann Maxillofac Surg 2012;2:46-50.
] [Full text]
Brescó-Salinas M, Costa-Riu N, Berini-Aytés L, Gay-Escoda C. Antibiotic susceptibility of the bacteria causing odontogenic infections. Med Oral Patol Oral Cir Bucal 2006;11:E70-5.
Kuriyama T, Karasawa T, Nakagawa K, Saiki Y, Yamamoto E, Nakamura S. Bacteriologic features and antimicrobial susceptibility in isolates from orofacial odontogenic infections. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:600-8.
Meinen A, Reuss A, Willrich N, Feig M, Noll I, Eckmanns T, et al.
Antimicrobial resistance and the spectrum of pathogens in dental and oral-maxillofacial infections in hospitals and dental practices in Germany. Front Microbiol 2021;12:676108.
Mahalle A, Deshmukh R, Mahalle A. Evaluating the antibiotic susceptibility of bacteria isolated from the pyogenic abscess of dental origin. J Dent Res Sci Dev 2014;1:6-10.
Jagadish Chandra H, Sripathi Rao BH, Muhammed Manzoor AP, Arun AB. Characterization and antibiotic sensitivity profile of bacteria in orofacial abscesses of odontogenic origin. J Maxillofac Oral Surg 2017;16:445-52.
Jindal S, Parmar S, Davessar J, Bawa AG, Singh G, Prinja S, et al
. A study of head and neck space infections and their sensitivity pattern at tertiary care hospital. Int J Otorhinolaryng Head Neck Surg 2019;5:165-71.
Shah A, Ramola V, Nautiyal V. Aerobic microbiology and culture sensitivity of head and neck space infection of odontogenic origin. Natl J Maxillofac Surg 2016;7:56-61.
] [Full text]
Al-Mehedi A, Chowdhury GM, Rab MA, Haider IA. Evaluation of efficiency of conventional empirical antimicrobial regimen for the management of maxillofacial fascial space infection. J Armed Forces Med Coll 2015;11:47-54.
Abdulla EH, Mohammed HY, Abdulaziz MI. Antibiotics sensitivity test as an important investigation measure in the management of odontogenic abscesses: Clinical study. Tikrit J Pure Sci 2009;14:18-20.
Prakash BG, Sowmya D, Prasad JR. A study of anaerobic infections and sensitivity pattern in neck abscess at tertiary hospital. Int J Cont Medi Resea 2016;3:1597-602.
Flynn TR. What are the antibiotics of choice for odontogenic infections, and how long should the treatment course last? Oral Maxillofac Surg Clin North Am 2011;23:519-36, v-vi.
Bascones Martínez A, Aguirre Urízar JM, Bermejo Fenoll A, Blanco Carrión A, Gay-Escoda C, González-Moles MA, et al.
Consensus statement on antimicrobial treatment of odontogenic bacterial infections. Med Oral Patol Oral Cir Bucal 2004;9:369-76.
Holmes CJ, Pellecchia R. Antimicrobial therapy in management of odontogenic infections in general dentistry. Dent Clin North Am 2016;60:497-507.
Löfmark S, Edlund C, Nord CE. Metronidazole is still the drug of choice for treatment of anaerobic infections. Clin Infect Dis 2010;50 Suppl 1:S16-23.
Chien JW, Kucia ML, Salata RA. Use of linezolid, an oxazolidinone, in the treatment of multidrug-resistant gram-positive bacterial infections. Clin Infect Dis 2000;30:146-51.
Lucena A, Dalla Costa LM, Nogueira KS, Matos AP, Gales AC, Paganini MC, et al.
Nosocomial infections with metallo-beta-lactamase-producing Pseudomonas aeruginosa
: Molecular epidemiology, risk factors, clinical features and outcomes. J Hosp Infect 2014;87:234-40.
Kuriyama T, Nakagawa K, Karasawa T, Saiki Y, Yamamoto E, Nakamura S. Past administration of β-lactam antibiotics and increase in the emergence of β-lactamase – Producing bacteria in patients with orofacial odontogenic infections. Ora Surg Oral Med Oral Pathol Ora Radiol Endod 2000;89:186-92.
Teoh L, Cheung MC, Dashper S, James R, McCullough MJ. Oral antibiotic for empirical management of acute dentoalveolar infections – A systematic review. Antibiot (Bas) 2021;10:240.
Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha A, Simonsen GS, et al.
Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European economic area in 2015: A population-level modelling analysis. Lancet Infect Dis 2019;19:56-66.
Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, et al.
Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 2018;18:318-27.
WHO. Antimicrobial Resistance: Global Report on Surveillance. Geneva: WHO; 2014. p. 1-256.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]