Standardized broth microdilution antimicrobial susceptibility testing of Francisella tularensis subsp. holarctica strains from Europe and rare Francisella species

Georgi, Enrico; Schacht, Erik; Scholz, Holger C.; Splettstoesser, Wolf D.

doi:10.1093/jac/dks238

Cited by 29 publications

(29 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…They included 107 type A, 789 type B and four F. tularensis subsp. mediasiatica strains (Table 1 and Table S1) (Scheel et al, 1993; Ikäheimo et al, 2000; Johansson et al, 2000, 2002; García del Blanco et al, 2004; Tomaso et al, 2005; Urich and Petersen, 2008; Valade et al, 2008; Velinov et al, 2011; Yeşilyurt et al, 2011; Georgi et al, 2012; Hotta et al, 2013; Kiliç et al, 2013; Kreizinger et al, 2013; Origgi et al, 2014). AST results were available for 33 antibiotics, although only some of them were tested in all studies (Tables 1– 5 and Table S1).…”

Section: Antibiotic Susceptibility Testing Of F Tularensismentioning

confidence: 99%

“…The broth microdilution technique using enriched caMHB medium should be considered the reference method. As recommended by the CLSI, a final inoculum calibrated at 5 10 5 CFU/mL should be used, as a 10-fold higher or lower inoculum is associated to interpretation errors (Georgi et al, 2012). However, the modified Mueller-Hinton II liquid medium should not be used for F. tularensis AST to avoid reporting MICs that could categorize F. tularensis strains as resistant to aminoglycosides or doxycycline whereas such resistances have never been characterized so far in this pathogen.…”

Section: General Conclusion and Perspectivesmentioning

confidence: 99%

See 1 more Smart Citation

Francisella tularensis Susceptibility to Antibiotics: A Comprehensive Review of the Data Obtained In vitro and in Animal Models

Caspar

Maurin

2017

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

The antibiotic classes that are recommended for tularaemia treatment are the aminoglycosides, the fluoroquinolones and the tetracyclines. However, cure rates vary between 60 and 100% depending on the antibiotic used, the time to appropriate antibiotic therapy setup and its duration, and the presence of complications, such as lymph node suppuration. Thus, antibiotic susceptibility testing (AST) of F. tularensis strains remains of primary importance for detection of the emergence of antibiotic resistances to first-line drugs, and to test new therapeutic alternatives. However, the AST methods reported in the literature were poorly standardized between studies and AST data have not been previously evaluated in a comprehensive and comparative way. The aim of the present review was to summarize experimental data on antibiotic susceptibilities of F. tularensis obtained in acellular media, cell models and animal models since the introduction of fluoroquinolones in the treatment of tularaemia in 1989. We compiled MIC data of 33 antibiotics (including aminoglycosides, fluoroquinolones, tetracyclines, macrolides, β-lactams, chloramphenicol, rifampicin, and linezolid) against 900 F. tularensis strains (504 human strains), including 107 subsp. tularensis (type A), 789 subsp. holarctica (type B) and four subsp. mediasiatica strains, using various AST methods. Specific culture media were identified or confirmed as unsuitable for AST of F. tularensis. Overall, MICs were the lowest for ciprofloxacin (≤ 0.002–0.125 mg/L) and levofloxacin, and ranged from ≤ 0.016 to 2 mg/L for gentamicin, and 0.064 to 4 mg/L for doxycycline. No resistant strain to any of these antibiotics was reported. Fluoroquinolones also exhibited a bactericidal activity against intracellular F. tularensis and lower relapse rates in animal models when compared with the bacteriostatic compound doxycycline. As expected, lower MIC values were found for macrolides against type A and biovar I type B strains, compared to biovar II type B strains. The macrolides were more effective against F. tularensis grown in phagocytic cells than in acellular media.

show abstract

Section: Antibiotic Susceptibility Testing Of F Tularensismentioning

confidence: 99%

Section: General Conclusion and Perspectivesmentioning

confidence: 99%

Francisella tularensis Susceptibility to Antibiotics: A Comprehensive Review of the Data Obtained In vitro and in Animal Models

Caspar

Maurin

2017

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Antibiotic resistance to frontline therapeutics recommended for treatment of tularemia has never been identified in naturally occurring strains of F. tularensis or F. novicida (Ikäheimo et al, 2000; Garcia Del Blanco et al, 2004; Tomaso et al, 2005; Urich and Petersen, 2008; Valade et al, 2008; Georgi et al, 2012). Although treatment failure has been documented for human cases of tularemia, it is not associated with spontaneous antibiotic resistance, but rather a delay in antibiotic initiation (Celebi et al, 2006; Meric et al, 2008; Kaya et al, 2011).…”

Section: Treatmentmentioning

confidence: 99%

Comparative review of Francisella tularensis and Francisella novicida

Kingry

Petersen

2014

Front. Cell. Infect. Microbiol.

171

209

View full text Add to dashboard Cite

Francisella tularensis is the causative agent of the acute disease tularemia. Due to its extreme infectivity and ability to cause disease upon inhalation, F. tularensis has been classified as a biothreat agent. Two subspecies of F. tularensis, tularensis and holarctica, are responsible for tularemia in humans. In comparison, the closely related species F. novicida very rarely causes human illness and cases that do occur are associated with patients who are immune compromised or have other underlying health problems. Virulence between F. tularensis and F. novicida also differs in laboratory animals. Despite this varying capacity to cause disease, the two species share ~97% nucleotide identity, with F. novicida commonly used as a laboratory surrogate for F. tularensis. As the F. novicida U112 strain is exempt from U.S. select agent regulations, research studies can be carried out in non-registered laboratories lacking specialized containment facilities required for work with virulent F. tularensis strains. This review is designed to highlight phenotypic (clinical, ecological, virulence, and pathogenic) and genomic differences between F. tularensis and F. novicida that warrant maintaining F. novicida and F. tularensis as separate species. Standardized nomenclature for F. novicida is critical for accurate interpretation of experimental results, limiting clinical confusion between F. novicida and F. tularensis and ensuring treatment efficacy studies utilize virulent F. tularensis strains.

show abstract

“…Variation due to distinct differences between the A and B strains may cause some B strain macrolide values to be in a poor activity range. Macrolide resistance has been observed with the B strains which are prevalent in Europe and, as a result, are contraindicated for treatment (8,10). With the exception of the macrolide distribution, no other differences were observed between A and B strains for other antibiotics.…”

mentioning

confidence: 99%

In Vitro Antibiotic Susceptibilities of Francisella tularensis Determined by Broth Microdilution following CLSI Methods

Heine

Miller

Halasohoris

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

In vitro susceptibilities for 47 antibiotics were determined in 30 genetic diverse strains of Francisella tularensis by the broth microdilution method following Clinical and Laboratory Standards Institute (CLSI) methods. The F. tularensis strains demonstrated susceptibility to aminoglycosides, fluoroquinolones, and tetracyclines. There was a distinct difference in macrolide susceptibilities between A and B type strains, as has been noted previously. The establishment and comparison of antibiotic susceptibilities of a diverse but specific set of F. tularensis strains by standardized methods and the establishment of population ranges and MIC 50/90 values provide reference information for assessing new antibiotic agents and a baseline to monitor any future emergence of resistance, whether natural or intentional.KEYWORDS Francisella tularensis, antibiotics, susceptibility testing F rancisella tularensis is the causative agent of tularemia, a zoonotic infection in humans, usually transmitted as a result of contact with infected animals or insect bites (1). It also has potential misuse in biowarfare and bioterrorism (2). While the disease is not usually fatal, underlying medical conditions can lead to possibly fatal complications. Antibiotic therapy usually resolves the infection (1). The species is also divided into several biovars, based on metabolic differences, virulence, and geographic location (3). There is scattered information on MICs under a variety of nonstandardized testing conditions, with mostly type B (F. tularensis subsp. holarctica) strains (4-15). A more recent report utilizing standardized testing methods with a variety of North American type A strains (16) has provided some additional data; however, this study looked at only eight antibiotics representing five classes. With a lack of comparative data on type strains and with a variety of antibiotic classes, we report here specific antibiotic susceptibility results according to Clinical and Laboratory Standards Institute (CLSI) microdilution broth methodology for 30 strains of F. tularensis (17). This information will be highly useful as baseline data in the event of wartime or terrorist release, as well as for naturally acquired and laboratory-acquired infections.The F. tularensis strains used in this study are shown in Table 1, and they were obtained from the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) collection and selected to represent the established biovars and geographic diversity (18). Most antibiotics were obtained from U.S. Pharmacopoeia (Rockville, MD), with the following exceptions: ceftriaxone and fusidic acid were from Sigma Chemical Co. (St. Louis, MO), cethromycin was from Advanced Life Sciences; telithromycin was from Sanofi-Aventis, garenoxacin was from Schering-Plough, gemifloxacin was from Oscient, ertapenem was from Merck, faropenem was from Replidyne, and tigecycline was from Wyeth. Most stock solutions (5 mg/ml) were prepared for each drug in the appropriate solvents, based on the current CLS...

show abstract

Standardized broth microdilution antimicrobial susceptibility testing of Francisella tularensis subsp. holarctica strains from Europe and rare Francisella species

Cited by 29 publications

References 20 publications

Francisella tularensis Susceptibility to Antibiotics: A Comprehensive Review of the Data Obtained In vitro and in Animal Models

Francisella tularensis Susceptibility to Antibiotics: A Comprehensive Review of the Data Obtained In vitro and in Animal Models

Comparative review of Francisella tularensis and Francisella novicida

In Vitro Antibiotic Susceptibilities of Francisella tularensis Determined by Broth Microdilution following CLSI Methods

Contact Info

Product

Resources

About