Reviving the role of mecillinam against extended spectrum beta-lactamase producing enterobacterales
-
Fatima Kaleem
,
Irum Aftab
,
Umme Farwa
,
Hassan Saleem
,
Saima Ishtiaq
,
Saima Syed
,
Shahid Ahmad Abbasi
Abstract
Background and Objectives: This study was designed to determine the in vitro efficacy of mecillinam against extended spectrum beta lactamse producing Enterobacterales.
Materials and Methods: After proper permission from Ethical Review Committee of the Institute, all samples yielding growth of ESBL producing Enterobacterales were part of the study and were processed according to routine microbiological procedures. Routine antibiotic sensitivity testing was done on Muller Hinton Agar by Modified Kirby Bauer Method. All Gram negative isolates were subjected to concomitant detection of ESBL production by double disc synergy method. All ESBL producers were then subjected to the mecillinam Minimum Inhibitory Concentration (MIC) determination by E test. The results were interpreted as per CLSI Guidelines.
Results: A total of 120 ESBL producing Enterobacterales isolates were included in the study. The mean age of patients with ESBL infection was 45 ± 18.7 years. There were 44% male and 55% female patients. Majority of the ESBL producing Enterobacterales were isolated from urine samples (56%), followed by pus. Among the isolated organisms, Escherichia coli (45%) was the most frequently isolated organism followed by Klebsiella spp. (22%). Overall 83% of the isolates turned out to be sensitive to mecillinam. MIC50 of mecillinam against ESBL producing Gram negative rods (GNR) turned out to be 1 ug/ml and MIC90 turned out to be 2 ug/ml.
Conclusion: Mecillinam shows good in vitro efficacy against ESBL producing Enterobacterales in our study. Further studies with more sample size and from diverse areas across the country should be done to evaluate its efficacy.
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8. D'Angelo RG , Johnson JK , Bork JT , Heil EL. Treatment options for extended-spectrum beta-lactamase (ESBL) and AmpC-producing bacteria. Expert Opin Pharmacother 2016; 17: 953-967.
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13. Logan LK, Weinstein RA. The epidemiology of carbapenem-resistant Enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis 2017; 215 (Suppl 1): S28-S36.
14. Mutters NT, Zimmermann S, Kaase M, Mischnik A. Activity of temocillin, mecillinam, ceftazidime, and ceftazidime/avibactam against carbapenem-non-susceptible Enterobacteriaceae without carbapenemase production. Eur J Clin Microbiol Infect Dis 2015; 34: 2429-2437·
15. Dewar S , Reed LC, Koerner RJ. Emerging clinical role of pivmecillinam in the treatment of urinary tract infection in the context of multidrug-resistant bacteria. J Antimicrob Chemother 2014; 69: 303-308.
16. Giske CG. Contemporary resistance trends and mechanisms for the old antibiotics colistin, temocillin, fosfomycin, mecillinam andnitrofurantoin. Clin Microbiol Infect 2015; 21: 899-905.
17. Karaiskos I, Lagou S, Pontikis K, Rapti V, Poulakou G. The "Old" and the "New" antibiotics for MDR Gram-Negative pathogens: For whom, when, and how. Front Public Health 2019; 7: 151.
18. Bollestad M, Grude N, Solhaug S, Raffelsberger N , Handal N , Nilsen H-JS, et al. Clinical and bacteriological efficacy of pivmecillinam treatment for uncomplicated urinary tract infections caused by ESBL-producing Escherichia coli: a prospective, multicentre, observational cohort study. J Antimicrob Chemother 2018; 73: 2503-2509.
19. Birgy A, Delecourt M, Geslain G, Desselas E, Caseris M, Magnan M, et al. A combination of Mecillinam and amoxicillin/Clavulanate can restore susceptibility of high-level TEM-1-producing Escherichia coli to Mecillinam. J Antimicrob Chemother 2017; 72: 1911-1914.
20. Thulin E, Sundqvist M, Andersson DI. Amdinocillin (Mecillinam) resistance mutations in clinical isolates and laboratory-selected mutants of Escherichia coli. Antimicrob Agents Chemother 2015; 59: 1718-1727.
21. Marrs ECL, Day KM, Perry JD. In vitro activity of mecillinam against Enterobacteriaceae with NDM-1 carbapenemase. J Antimicrob Chemother 2014; 69: 2873-2875.
22. Salomonsson P, Von Linstow M-L, Knudsen JD, Heiberg I, Mola G, Wenger TR, et al. Best oral empirical treatment for pyelonephritis in children: do we need to differentiate between age and gender? Infect Dis (Lond) 2016; 48: 721-725.
23. Jansaker F, Boetius Hertz F, Frimodt-moller N, Dahl Knudsen J. Pivmecillinam treatment of community-acquired uncomplicated pyelonephritis based on sparse data. Glob J Infect Dis Clin Res 2015; 1: 014-017.
24. Chin TL, McNulty C, Beck C, MacGowan A. Antimicrobial resistance surveillance in urinary tract infections in primary care. J Antimicrob Chemother 2016; 71: 2723-2728.
25. Soraas A, Sundsfjord A, Jorgensen SB, Liestol K, Jenum PA. High rate of per oral mecillinam treatment failure in community-acquired urinary tract infections caused by ESBL-producing Escherichia coli. PLoS One 2014; 9(1): e85889.
26. Fleming A, Barry L, Byrne S, Prentice M. Antimicrobial susceptibility of long term care facility and general practice urine samples in patients 65 years and older: an observational study. Eur J Public Health 2017; 27: 307-312.
27. Montelin H, Forsman K-J, Tangden T. Retrospective evaluation of nitrofurantoin and pivmecillinam for the treatment of lower urinary tract infections in men. PLoS One 2019; 14(1): e0211098.
28. Jansåker F, Frimodt-Møller N, Sjögren I, Dahl Knudsen J. Clinical and bacteriological effects of pivmecillinam for ESBL-producing Escherichia coli or Klebsiella pneumoniae in urinary tract infections. J Antimicrob Chemother 2014; 69: 769-772.
29. Lampri N, Galani I, Poulakou G, Katsarolis I, Petrikkos G, Giamarellou H, et al. Mecillinam/clavulanate combination: a possible option for the treatment of community-acquired uncomplicated urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli. J Antimicrob Chemother 2012; 67: 2424-2428.
30. Graninger W. Pivmecillinam--therapy of choice for lower urinary tract infection. Int J Antimicrob Agents 2003; 22 Suppl 2: 73-78.
31. Fuchs F, Ahmadzada A, Plambeck L, Wille T, Hamprecht A. Susceptibility of clinical Enterobacterales isolates with common and rare carbapenemases to mecillinam. Front Microbiol 2021; 11: 627267.
32. Wootton M, Walsh TR, Macfarlane L, Howe RA. Activity of mecillinam against Escherichia coli resistant to third-generation cephalosporins. J Antimicrob Chemother 2010: 65: 79-81.
2. Jansker F, Frimodt-Møller N, Benfield TL, Knudsen JD. Mecillinam for the treatment of acute pyelonephritis and bacteremia caused by Enterobacteriaceae: a literature review. Infect Drug Resist 2018; 11: 761-771.
3. Wassef M, Behiry I, Younan M, El Guindy N, Mostafa S, Abada E. Genotypic Identification of AmpC β-Lactamases production in Gram-negative bacilli isolates. Jundishapur J Microbiol 2014; 7(1): e8556.
4. Thulin E, Thulin M, Andersson DI. Reversion of high-level Mecillinam resistance to susceptibility in Escherichia coli during growth in urine. EBioMedicine 2017; 23: 111-118.
5. Abrar S, Hussain S, Khan RA, Ul Ain N, Haider H, Riaz S. Prevalence of extended-spectrum-β-lactamase-producing Enterobacteriaceae: first systematic meta-analysis report from Pakistan. Antimicrob Resist Infect Control 2018; 7: 26.
6. Iqbal R. Determination of epidemiology and antimicrobial susceptibility of extended spectrum beta lactamase producing uropathogens. J Pak Med Assoc 2019; 69: 690-694.
7. Zykov IN, Sundsfjord A, Smabrekke L, Samuelsen O. The antimicrobial activity of Mecillinam, nitrofurantoin, temocillin and fosfomycin and comparative analysis of resistance patterns in a nationwide collection of ESBL-producing Escherichia coli in Norway 2010–2011. Infect Dis (Lond) 2016; 48: 99-107.
8. D'Angelo RG , Johnson JK , Bork JT , Heil EL. Treatment options for extended-spectrum beta-lactamase (ESBL) and AmpC-producing bacteria. Expert Opin Pharmacother 2016; 17: 953-967.
9. Salamat S, Ejaz H, Zafar A, Javed H. Detection of AmpC β-lactamase producing bacteria isolated in neonatal sepsis. Pak J Med Sci 2016; 32: 1512- 1516.
10. Lee C-S, Doi Y. Therapy of infections due to carbapenem-resistant Gram-negative pathogens. Infect Chemother 2014; 46: 149-164.
11. CLSI. Performance standards for Antimicrobial Susceptibility Testing. 31st ed. CLSI standards M02 and M07. Wayne PA: Clinical and Laboratory Standards Institute; 2021.
12. Monsen TJ, Holm SE, Ferry BM, Ferry SA. Mecillinam resistance and outcome of pivmecillinam treatment in uncomplicated lower urinary tract infection in women. APMIS 2014; 122: 317-323.
13. Logan LK, Weinstein RA. The epidemiology of carbapenem-resistant Enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis 2017; 215 (Suppl 1): S28-S36.
14. Mutters NT, Zimmermann S, Kaase M, Mischnik A. Activity of temocillin, mecillinam, ceftazidime, and ceftazidime/avibactam against carbapenem-non-susceptible Enterobacteriaceae without carbapenemase production. Eur J Clin Microbiol Infect Dis 2015; 34: 2429-2437·
15. Dewar S , Reed LC, Koerner RJ. Emerging clinical role of pivmecillinam in the treatment of urinary tract infection in the context of multidrug-resistant bacteria. J Antimicrob Chemother 2014; 69: 303-308.
16. Giske CG. Contemporary resistance trends and mechanisms for the old antibiotics colistin, temocillin, fosfomycin, mecillinam andnitrofurantoin. Clin Microbiol Infect 2015; 21: 899-905.
17. Karaiskos I, Lagou S, Pontikis K, Rapti V, Poulakou G. The "Old" and the "New" antibiotics for MDR Gram-Negative pathogens: For whom, when, and how. Front Public Health 2019; 7: 151.
18. Bollestad M, Grude N, Solhaug S, Raffelsberger N , Handal N , Nilsen H-JS, et al. Clinical and bacteriological efficacy of pivmecillinam treatment for uncomplicated urinary tract infections caused by ESBL-producing Escherichia coli: a prospective, multicentre, observational cohort study. J Antimicrob Chemother 2018; 73: 2503-2509.
19. Birgy A, Delecourt M, Geslain G, Desselas E, Caseris M, Magnan M, et al. A combination of Mecillinam and amoxicillin/Clavulanate can restore susceptibility of high-level TEM-1-producing Escherichia coli to Mecillinam. J Antimicrob Chemother 2017; 72: 1911-1914.
20. Thulin E, Sundqvist M, Andersson DI. Amdinocillin (Mecillinam) resistance mutations in clinical isolates and laboratory-selected mutants of Escherichia coli. Antimicrob Agents Chemother 2015; 59: 1718-1727.
21. Marrs ECL, Day KM, Perry JD. In vitro activity of mecillinam against Enterobacteriaceae with NDM-1 carbapenemase. J Antimicrob Chemother 2014; 69: 2873-2875.
22. Salomonsson P, Von Linstow M-L, Knudsen JD, Heiberg I, Mola G, Wenger TR, et al. Best oral empirical treatment for pyelonephritis in children: do we need to differentiate between age and gender? Infect Dis (Lond) 2016; 48: 721-725.
23. Jansaker F, Boetius Hertz F, Frimodt-moller N, Dahl Knudsen J. Pivmecillinam treatment of community-acquired uncomplicated pyelonephritis based on sparse data. Glob J Infect Dis Clin Res 2015; 1: 014-017.
24. Chin TL, McNulty C, Beck C, MacGowan A. Antimicrobial resistance surveillance in urinary tract infections in primary care. J Antimicrob Chemother 2016; 71: 2723-2728.
25. Soraas A, Sundsfjord A, Jorgensen SB, Liestol K, Jenum PA. High rate of per oral mecillinam treatment failure in community-acquired urinary tract infections caused by ESBL-producing Escherichia coli. PLoS One 2014; 9(1): e85889.
26. Fleming A, Barry L, Byrne S, Prentice M. Antimicrobial susceptibility of long term care facility and general practice urine samples in patients 65 years and older: an observational study. Eur J Public Health 2017; 27: 307-312.
27. Montelin H, Forsman K-J, Tangden T. Retrospective evaluation of nitrofurantoin and pivmecillinam for the treatment of lower urinary tract infections in men. PLoS One 2019; 14(1): e0211098.
28. Jansåker F, Frimodt-Møller N, Sjögren I, Dahl Knudsen J. Clinical and bacteriological effects of pivmecillinam for ESBL-producing Escherichia coli or Klebsiella pneumoniae in urinary tract infections. J Antimicrob Chemother 2014; 69: 769-772.
29. Lampri N, Galani I, Poulakou G, Katsarolis I, Petrikkos G, Giamarellou H, et al. Mecillinam/clavulanate combination: a possible option for the treatment of community-acquired uncomplicated urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli. J Antimicrob Chemother 2012; 67: 2424-2428.
30. Graninger W. Pivmecillinam--therapy of choice for lower urinary tract infection. Int J Antimicrob Agents 2003; 22 Suppl 2: 73-78.
31. Fuchs F, Ahmadzada A, Plambeck L, Wille T, Hamprecht A. Susceptibility of clinical Enterobacterales isolates with common and rare carbapenemases to mecillinam. Front Microbiol 2021; 11: 627267.
32. Wootton M, Walsh TR, Macfarlane L, Howe RA. Activity of mecillinam against Escherichia coli resistant to third-generation cephalosporins. J Antimicrob Chemother 2010: 65: 79-81.
| Files | ||
| Issue | Vol 14 No 5 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v14i5.10959 | |
| Keywords | ||
| Extended spectrum β-lactamase; In vitro susceptibility | ||
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How to Cite
1.
Kaleem F, Aftab I, Farwa U, Saleem H, Ishtiaq S, Syed S, Abbasi SA. Reviving the role of mecillinam against extended spectrum beta-lactamase producing enterobacterales. Iran J Microbiol. 2022;14(5):662-668.
