Urinary tract infections (UTIs) are the most frequent human infections in community and hospitals. This study aimed to determine the distribution of bacterial uropathogens among urinary tract infections diagnosed within the regional hospital Houcine Bouzaiene (Gafsa, South West Tunisia) during a survey of 54 days from the 8th of November to the 31st of December 2017. Enterobacterales strains were tested for antimicrobial resistance by disk diffusion method and extended-spectrum β-lactamase (ESBL) production was tested by double-disc synergy test. Strains were further subjected to a molecular assessment of ESBL and AmpC β-lactamase production by PCR.
Overall, 173 bacterial isolates were studied, out of which 91.3% were Enterobacterales. Escherichia coli was the dominant pathogen, followed by Klebsiella pneumoniae. High to moderate resistance rates were observed, ranging from 66% to 90.7% for penicillins, from 6.7% to 18.6% for cephalosporins and from 16.2% to 25.4% for fluoroquinolones. Enterobacterales with decreased susceptibility to third-generation cephalosporins (3rd GC) carried several resistance genes: blaCTX-M group 1 and group 9, and ACC and FOX AmpC β-lactamase genes. Overall, ESBLs and AmpC β-lactamases were detected in 57% and 14% of the 3rd GC-resistant isolates, respectively.
This study proved the high potential of K. pneumaniae species to develop resistance against commonly used antibiotics. Thus, rigorous monitoring of the antibiotic resistance of clinical pathogens have to be implemented in Tunisia. Our results are very relevant to evaluate efficiency of the Tunisian therapeutic strategies against UTIs and adapt them to the emerging problem of antimicrobial resistance.
IACG: Interagency Coordination Group IACG on Antimicrobial Resistance . No time to wait: securing the future from drug-resistant infections. Report to the Secretary-General of the United Nations; 2019. Available from: https://www.who.int/antimicrobial-resistance/interagency-coordination-group/IACG_final_report_EN.pdf?ua=1 [Accessed 20 Apr 2021].
World Health Organization . Antimicrobial resistance global report on surveillance: summary; 2014. Available from: https://apps.who.int/iris/bitstream/handle/10665/112642/9789241564748_eng.pdf;jsessionid=EAA07626A2FE319D6D92D5A157C5F382?sequence=1 [Accessed 20 Apr 2021].
World Health Organization . Antimicrobial resistance: key facts; 2020. Available from: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance [Accessed 20 Apr 2021].
Belachew SA , Hall L , Selvey LA . Non-prescription dispensing of antibiotic agents among community drug retail outlets in Sub-Saharan African countries: a systematic review and meta-analysis. Antimicrob Res Infect Control 2021; 10(1): 13.
Mathlouthi N , Al-Bayssari C , El Salabi A , Bakour S , Gwierif SB , Zorgani AA , et al. Carbapenemases and extended-spectrum β-lactamases producing Enterobacteriaceae isolated from Tunisian and Libyan hospitals. J Infect Dev Ctries 2016; 10(07): 718–727.
Burnham CAD , Leeds J , Nordmann P , O’Grady J , Patel J . Diagnosing antimicrobial resistance. Nat Rev Microbiol 2017; 15(11): 697–703.
Carroll S P , SøgaardJørgensen P , Kinnison MT , Bergstrom CT , Denison RF , Gluckman P , et al. Applying evolutionary biology to address global challenges. Science 2014; 346(6207): 1245993.
Dhawale A , Rath A . Antibiotic resistance: a threat and challenge to society. Ann Appl Bio-Sciences 2014; 1: R1–R6.
Correa-Martínez CL , Idelevich EA , Sparbier K , Kostrzewa M , Becker K . Rapid detection of extended-spectrum β-lactamases (ESBL) and AmpCβ-lactamases in Enterobacterales: development of a screening panel using the MALDI-TOF MS-based direct-on-target microdroplet growth assay. Front Microbiol 2019; 10: 13.
Gajamer VR , Bhattacharjee A , Paul D , Ingti B , Sarkar A , Kapil J , et al. High prevalence of carbapenemase, AmpC β-lactamase and aminoglycoside resistance genes in extended-spectrum β-lactamase-positive uropathogens from Northern India. J Glob Antimicrob Resist 2020; 20: 197–203.
Khoshnood S , Heidary M , Mirnejad R , Bahramian A , Sedighi M , Mirzaei H . Drug-resistant gram-negative uropathogens: a review. Biomed Pharmacother 2017; 94: 982–994.
Teklu DS , Negeri AA , Legese MH , Bedada TL , Woldemariam HK , Tullu KD . Extended-spectrum beta-lactamase production and multi-drug resistance among Enterobacteriaceae isolated in Addis Ababa, Ethiopia. Antimicrob Resist Infect Control 2019; 8(1): 39.
Bouallègue O , Saidani M , Mohamd SB , Mzoughi R . Bacteriologic features of urinary tract infections in children in the Sousse area, Tunisia. Tunis Med 2004; 82(8): 742–746.
Daoud N , Hamdoun M , Hannachi H , Gharsallah C , Mallekh W , Bahri O . Antimicrobial susceptibility patterns of Escherichia coli among Tunisian outpatients with community-acquired urinary tract infection (2012–2018). Curr Urol 2020; 14(4): 200–205.
Larabi K , Masmoudi A , Fendri C . Étude bactériologique et phénotypes de résistance des germes responsables d’infections urinaires dans un CHU de Tunis: à propos de 1930 cas. Med Mal Infect 2003; 33(7): 348–352.
Najwa D , Salah AM , Yolanda S , Monia K , Dorsaf M , Chiheb BR , et al. Low antibiotic resistance rates and high genetic heterogeneity of Escherichia coli isolates from urinary tract infections of diabetic patients in Tunisia. J Chemother 2016; 28(2): 89–94.
Thabet L , Messadi AA , Meddeb B , Mbarek M , Turki A , Redjeb B . Bacteriological profile of urinary tract infections in women in Aziza Othmana Hospital: 495 cases. Tunis Med 2010; 88(12): 898–901.
Guermazi-Toumi S , Boujlel S , Assoudi M , Issaoui R , Tlili S , Hlaiem ME . Susceptibility profiles of bacteria causing urinary tract infections in Southern Tunisia. J Glob Antimicrob Resist 2018; 12: 48–52.
Smaoui S , Abdelhedi K , Marouane C , Kammoun S , Messadi-Akrout F . Antibiotic resistance of community-acquired uropathogenic Enterobacteriaceae isolated in Sfax (Tunisia). Med Mal Infect 2015; 45(8): 335–337.
Dallenne C , Da Costa A , Decré D , Favier C , Arlet G . Development of a set of multiplex PCR assays for the detection of genes encoding important β-lactamases in Enterobacteriaceae. J Antimicrob Chemother 2010; 65(3): 490–495.
Ribot EM , Fair MA , Gautom R , Cameron DN , Hunter SB , Swaminathan B , et al. Standardization of pulsed-field gel electrophoresis protocols for the subtyping of Escherichia coli O157: H7, Salmonella, and Shigella for PulseNet. Foodbourne Pathog Dis 2006; 3(1): 59–67.
Cao X , Zhang Z , Shen H , Ning M , Chen J , Wei H , et al. Genotypic characteristics of multidrug-resistant Escherichia coli isolates associated with urinary tract infections. APMIS 2014; 122(11): 1088–1095.
Raeispour M , Ranjbar R . Antibiotic resistance, virulence factors and genotyping of Uropathogenic Escherichia coli strains. Antimicrob Resist Infect Control 2018; 7(1): 118.
Chervet D , Lortholary O , Zahar JR , Dufougeray A , Pilmis B , Partouche, H . Antimicrobial resistance in community-acquired urinary tract infections in Paris in 2015. Med Mal Infect 2018; 48(3): 188–192.
Khan MI , Xu S , Ali MM , Ali R , Kazmi A , Akhtar N , et al. Assessment of multi-drug resistance in bacterial isolates from urinary tract-infected patients. J Radiat Res Appl Sci 2020; 13(1): 267–275.
Mohamed ES , Khairy RM , Abdelrahim SS . Prevalence and molecular characteristics of ESBL and AmpC β-lactamase producing Enterobacteriaceae strains isolated from UTIs in Egypt. Antimicrob Resist Infect Control 2020; 9(1): 1–9.
Rafalskiy V , Pushkar D , Yakovlev S , Epstein O , Putilovskiy M , Tarasov S , et al. Distribution and antibiotic resistance profile of key Gram-negative bacteria that cause community-onset urinary tract infections in the Russian Federation: RESOURCE multicentre surveillance 2017 study. J Glob Antimicrob Resist 2020; 21: 188–194.
Saliba W , Fediai A , Edelstein H , Markel A . Trends in the burden of infectious disease hospitalizations among the eldery in the last decade. Eur J Inter Med 2013; 24: 536–540.
El Bouamri MC , Arsalane L , El Kamouni Y , Zouhair S . Antimicrobial susceptibility of urinary Klebsiella pneumoniae and the emergence of carbapenem-resistant strains: a retrospective study from a university hospital in Morocco, North Africa. Afr J Urol 2015; 21(1): 36–40.
Dinah M , Scholastica M , Arodi W , Torome T , Oliver M , Martin K . Antibiotic susceptibility pattern among male patients with urinary tract infection in special treatment center Nairobi, Kenya. Int J Adv Multidisciplinary Res 2019; 6: 36–41.
Ganesh R , Shrestha D , Bhattachan B , Rai G . Epidemiology of urinary tract infection and antimicrobial resistance in a pediatric hospital in Nepal. BMC Infect Dis 2019; 19: 420.
Tomy A , Hareendran A , David E , Ravi R , Ramachandran L . Thomas A . Antimicrobial susceptibility of uropathogens and prescribing patterns in hospital-and community-acquired urinary tract infections in a tertiary care hospital. J Appl Pharm Sci 2020; 10(11): 050–058.
Vakilzadeh MM , Heidari A , Mehri A , Shirazinia M , Sheybani F , Aryan E , et al. Antimicrobial resistance among community-acquired uropathogens in Mashhad, Iran. J Environ Public Health 2020; 2020: 3439497.
Mohammed MA , Alnour TM , Shakurfo OM , Aburass MM . Prevalence and antimicrobial resistance pattern of bacterial strains isolated from patients with urinary tract infection in Messalata Central Hospital, Libya. Asian Pac J Trop Med 2016; 9(8): 771–776.
Mothibi LM , Bosman NN , Nana T . Fosfomycin susceptibility of uropathogens at Charlotte Maxeke Johannesburg Academic hospital. S Afr J Infect Dis 2020; 35(1).
Mowlaboccus S , Daley D , Pang S , Gottlieb T , Merlino J , Nimmo GR , et al. Identification and characterisation of fosfomycin resistance in Escherichia coli urinary tract infection isolates from Australia. Int J Antimicrob Agents 2020; 56(4): 106121.
Raz R. Fosfomycin: an old—new antibiotic. Clin Microbiol Infect 2012; 18(1): 4–7.
STPI . Société Tunisienne de Pathologie Infectieuse: antibiothérapie des infections urinaires communautaires de l’adulte. Recommandations de la STPI; 2018. Available at: https://www.infectiologie.org.tn/pdf_ppt_docs/recommandations/1527103156.pdf [Last accessed 20 Apr 2021].
Linhares I , Raposo T , Rodrigues A , Almeida A . Incidence and diversity of antimicrobial multi-drug resistance profiles of uropathogenic bacteria. BioMed Res Int 2015; 2015: 354084.
Navon-Venezia S , Kondratyeva K , Carattoli A . Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol Rev 2017; 41(3): 252–275.
Dahmen S , Bettaieb D , Mansour W , Boujaafar N , Bouallegue O , Arlet G . Characterization and molecular epidemiology of extended-spectrum β-lactamases in clinical isolates of Enterobacteriaceae in a Tunisian University hospital. Microb Drug Res 2010; 16(2): 163–170.
Guiral E , Pons MJ , Vubil D , Marí-Almirall M , Sigaúque B , Soto SM , et al. Epidemiology and molecular characterization of multidrug-resistant Escherichia coli isolates harbouring blaCTX-M group 1 extended-spectrum β-lactamases causing bacteremia and urinary tract infection in Manhiça, Mozambique. Infect Drug Resist 2018; 11: 927–936.
Hagen RM , Hinz H , Frickmann H . β-lactamases encoded by bla CTX-M group I genes as determinants of resistance of ESBL-positive enterobacteriaceae in European soldiers in tropical Mali. Eur J Microbiol Immunol (Bp) 2015; 5(4): 281–284.
Hammami S , Saidani M , Ferjeni S , Aissa I , Slim A , Boutiba-Ben Boubaker I . Characterization of extended spectrum β-lactamase-producing Escherichia coli in community-acquired urinary tract infections in Tunisia. Microb Drug Resist 2013; 19(3): 231–236.
Peerayeh SN , Eslami M , Memariani M , Siadat SD . High prevalence of blaCTX-M-1 group extended-spectrum β-lactamase genes in Escherichia coli isolates from Tehran. Jundishapur J Microbiol 2013; 6(7): 1–6.
Woodford N , Ward ME , Kaufmann ME , Turton J , Fagan EJ , James D , et al. Community and hospital spread of Escherichia coli producing CTX-M extended-spectrum β-lactamases in the UK. J Antimicrob Chemother 2004; 54(4): 735–743.
Galvis SF , Moreno RL . Molecular characterization and detection of genes blaCTX-M groups 1 and 9 in Klebsiella pneumoniae resistant to ceftazidime, in a hospital in San José de Cúcuta, Colombia. Revista Chilena de Infectologia: Organo Oficial de la Sociedad Chilena de Infectologia 2019; 36(3): 304–311.
Hussein AA , Al-Mayahie SMG . High distribution of AmpC-type ESBLs among Escherichia coli isolates from outpatients with urinary tract infection in wasit Province, Iraq. Indian J Nat Sci 2019; 9: 17545–17554.
Sangeetha K , SM, R , Ravi GS , Raksha Y . Urinary tract infections due to Amp C b-Lactamase producing gram negative bacteria. Res J Med Allied Health Sci 2019; 2: 15–18.
Fam N , Gamal D , El Said M , El Defrawy I , El Dadei E , El Attar S , et al. Prevalence of plasmid-mediated ampC genes in clinical isolates of Enterobacteriaceae from Cairo, Egypt. Microbiol Res J Int 2013; 3: 525–537.
Ben Tanfous F , Alonso CA , Achour W , Ruiz-Ripa L , Torres C , Ben Hassen A . First description of KPC-2-producing Escherichia coli and ST15 OXA-48-positive Klebsiella pneumoniae in Tunisia. Microb Drug Resist 2017; 23(3): 365–375.
Chérif T , Saidani M , Decré D , Boubaker IBB , Arlet G . Cooccurrence of multiple AmpC β-lactamases in Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis in Tunisia. Antimicrob Agents Chemother 2016:60(1): 44–51.
Ghane M , Babaeekhou L , Jafar Shanjan, M . AmpC β lactamases in urinary Klebsiella pneumoniae isolates: first report of ACC type AmpC β-lactamase resistance in Iran. J Adv Med Biomed Res 2019; 27(123): 23–30.
Helmy MM , Wasfi R . Phenotypic and molecular characterization of plasmid mediated AmpC β-lactamases among Escherichia coli, Klebsiella spp., and Proteus mirabilis isolated from urinary tract infections in Egyptian hospitals. BioMed Res Int 2014; 2014: 171548.
Motamedifar M , Mohebi S , Hadadi M , Amirzadegan H . The prevalence of ESBL and AmpC β-lactamases in uropathogenic isolates of Escherichia coli in a tertiary care hospital in Southwest Iran. Gene Rep 2020; 100747: 1–4.
Zorgani A , Daw H , Sufya N , Bashein A , Elahmer O , Chouchani C . Co-occurrence of plasmid-mediated AmpC β-lactamase activity among Klebsiella pneumoniae and Escherichia coli. Open Microbiol J 2017; 11: 195–202.
Said LB , Jouini A , Klibi N , Dziri R , Alonso CA , Boudabous A , et al. Detection of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in vegetables, soil and water of the farm environment in Tunisia. Int J Food Microbiol 2015; 203: 86–92.
Said LB , Jouini A , Alonso CA , Klibi N , Dziri R , Boudabous A , et al. Characteristics of extended-spectrum β-lactamase (ESBL)-and pAmpC beta-lactamase-producing Enterobacteriaceae of water samples in Tunisia. Sci Total Environ 2016; 550: 1103–1109.
Hassena AB , Siala M , Guermazi S , Zormati S , Gdoura R , Sellami H . Occurrence and phenotypic and molecular characterization of antimicrobial resistance of Salmonella isolates from food in Tunisia. J Food Prot 2019; 82(7): 1166–1175.
Dziri O , Dziri R , El Salab AA , Chouchani C . Carbapenemase producing gram-negative bacteria in Tunisia: History of Thirteen Years of challenge. Infect Drug Resist 2020; 13: 4177–4191.
Liao K , Chen Y , Wang M , Guo P , Yang Q , Ni Y , et al. Molecular characteristics of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae causing intra-abdominal infections from 9 tertiary hospitals in China. Diagn Microbiol Infect Dis 2017; 87(1): 45–48.
Azimzadeh N , Derakhshandeh A , Motamedifar M , Naziri Z . Clonal relatedness, Phylotyping and antimicrobial susceptibility of extended-spectrum-beta-lactamase producing uropathogenic Escherichia coli isolates from outpatients and inpatients. Infect Disord Drug Targets 2020; 20(5): 659–666.