Antimicrobial susceptibility and synergy studies of cystic fibrosis sputum by direct sputum sensitivity testing

Serisier, David J.; Tuck, Andrew; Matley, D.; Carroll, Mary; Jones, Graeme R.

doi:10.1007/s10096-012-1687-6

Cited by 11 publications

(10 citation statements)

References 20 publications

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“…Serisier et al (16) found such a medium to increase the susceptibility of P. aeruginosa to antibacterial inhibition, which is the same effect that we found with an antifungal. Davis and Bruns (18) found that the minimum bactericidal concentration increased for some antibacterials, which is remarkably also the same effect that we found with an antifungal; however, there was no change in killing with some other antibacterials (18).…”

Section: Discussionsupporting

confidence: 89%

“…For that reason, various researchers have attempted to devise media for use in the laboratory that more closely approximate the milieu of CF airways for purposes of susceptibility testing, as well as studying growth, physiology, mutability, etc., of P. aeruginosa under such conditions. Such media have been shown to give disparate results from those obtained for P. aeruginosa using classical methods (16), such as the methods and medium of the Clinical and Laboratory Standards Institute.…”

mentioning

confidence: 99%

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Effect of Media Modified To Mimic Cystic Fibrosis Sputum on the Susceptibility of Aspergillus fumigatus, and the Frequency of Resistance at One Center

Stevens

Moss

Hernandez

et al. 2016

Antimicrob Agents Chemother

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c Studies of cystic fibrosis (CF) patient exacerbations attributed to Pseudomonas aeruginosa infection have indicated a lack of correlation of outcome with in vitro susceptibility results. One explanation is that the media used for testing do not mimic the airway milieu, resulting in incorrect conclusions. Therefore, media have been devised to mimic CF sputum. Aspergillus fumigatus is the leading fungal pathogen in CF, and susceptibility testing is also used to decide therapeutic choices. We assessed whether media designed to mimic CF sputa would give different fungal susceptibility results than those of classical methods, assaying voriconazole, the most utilized anti-Aspergillus drug in this setting, and 30 CF Aspergillus isolates. The frequency of marked resistance (defined as an MIC of >4 g/ml) in our CF unit by classical methods is 7%. Studies performed with classical methods and with digested sputum medium, synthetic sputum medium, and artificial sputum medium revealed prominent differences in Aspergillus susceptibility results, as well as growth rate, with each medium. Clinical correlative studies are required to determine which results are most useful in predicting outcome. Comparison of MICs with non-CF isolates also indicated the CF isolates were generally more resistant. C ystic fibrosis (CF) is a genetic disorder in epithelial anion transport. One result is the development of thick respiratory secretions, which are associated with repeated pulmonary infections and inflammation. The most common bacterium associated with these infections is Pseudomonas aeruginosa. The most common fungal pathogen associated with CF airways is Aspergillus fumigatus. Infection with either has been associated with worsened or a more rapid decline in CF pulmonary function (1-11), with coinfected patients having the worst prognosis (9, 12). In addition, Aspergillus fumigatus causes an allergic bronchopulmonary disease in up to 15% of CF patients (13).An important observation made with respect to Pseudomonas aeruginosa infection in CF patients is the lack of correlation of classical in vitro susceptibility testing of isolates from patients with exacerbations with the treatment outcomes in such patients (14,15). One logical explanation for that dissociation is that classical in vitro susceptibility testing does not mimic the conditions present in CF airways, thus leading to erroneous conclusions with respect to the activity of various antibacterials. For that reason, various researchers have attempted to devise media for use in the laboratory that more closely approximate the milieu of CF airways for purposes of susceptibility testing, as well as studying growth, physiology, mutability, etc., of P. aeruginosa under such conditions. Such media have been shown to give disparate results from those obtained for P. aeruginosa using classical methods (16), such as the methods and medium of the Clinical and Laboratory Standards Institute.With standardization of susceptibility testing for fungi, we wondered whether the routine in vitro...

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Effect of Media Modified To Mimic Cystic Fibrosis Sputum on the Susceptibility of Aspergillus fumigatus, and the Frequency of Resistance at One Center

Stevens

Moss

Hernandez

et al. 2016

Antimicrob Agents Chemother

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“…Our study thus showed that Achromobacter spp. are CF pathogens, for which the intrasample and the intramorphotype antimicrobial susceptibility diversity leads to an underestimation of antibiotic resistance and impairs current strategies of antimicrobial susceptibility testing on each colonial morphotype (10,30). Consequently, some authors have suggested that performing direct sputum susceptibility testing may be more accurate and may overcome the impact of resistance phenotype diversity (30,31).…”

Section: Discussionmentioning

confidence: 99%

Impact of High Diversity of Achromobacter Populations within Cystic Fibrosis Sputum Samples on Antimicrobial Susceptibility Testing

et al. 2017

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Chronic colonization by opportunistic environmental bacteria is frequent in the airways of cystic fibrosis (CF) patients. Studies of Pseudomonas aeruginosa evolution during persistence have highlighted the emergence of pathoadaptive genotypes and phenotypes, leading to complex and diversified inpatient colonizing populations also observed at the intraspecimen level. Such diversity, including heterogeneity in resistance profiles, has been considered an adaptive strategy devoted to host persistence. Longitudinal genomic diversity has been shown for the emergent opportunistic pathogen Achromobacter, but phenotypic and genomic diversity has not yet been studied within a simple CF sputum sample. Here, we studied the genomic diversity and antimicrobial resistance heterogeneity of 132 Achromobacter species strains (8 to 27 strains of identical or distinct colonial morphotypes per specimen) recovered from the sputum samples of 9 chronically colonized CF patients. We highlighted the high within-sample and within-morphotype diversity of antimicrobial resistance (disk diffusion) and genomic (pulsed-field gel electrophoresis) profiles. No sputum sample included strains with identical pulsotypes or antibiotic susceptibility patterns. Differences in clinical categorization were observed for the 9 patients and concerned 3 to 11 antibiotics, including antibiotics recommended for use against Achromobacter. Within-sample antimicrobial resistance heterogeneity, not predictable from colonial morphology, suggested that it may represent a selective advantage against antibiotics in an Achromobacter persisting population and potentially compromise the antibiotic management of CF airway infections.KEYWORDS Achromobacter, antimicrobial susceptibility, cystic fibrosis, diversity, genome B acterial adaptation during persistence in the respiratory tract of cystic fibrosis (CF) patients has mainly been studied for Pseudomonas aeruginosa showing that pathoadaptation mechanisms are particularly efficient, leading to rare and hardly achievable P. aeruginosa eradication. Many studies have revealed a variety of phenotypic pathoadaptative traits during long-term colonization, such as auxotrophy and metabolic modifications, quorum-sensing alterations, biofilm production, loss of motility and virulence factors, emergence of mucoid colonies, and an increase of antibiotic resistance (for a review, see reference 1). Moreover, numerous genomic modifications, which were either directly related to phenotype or not, were observed (1, 2). Other species, such as the Burkholderia cepacia complex, Stenotrophomonas maltophilia, and

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“…This lack of concordance between in vitro tests and clinical outcomes may be as a result of standard in vitro culture methods not accurately reflecting the highly complex microbial community or environmental conditions found in the CF lung. Relevant issues include the inherent phenotypic diversity and instability within a chronically infecting P. aeruginosa population, biofilm growth, anaerobic/microaerophilic conditions, niche-specific nutrition and metabolism, and potential interspecies interactions [54][55][56][57][58]. Furthermore, attempts to develop more clinically relevant susceptibility tests through combination [59,60] or biofilm [56,[61][62][63] directed testing have shown no consistent improvement in clinical or bacteriological outcome.…”

Section: In Vitro Antibiotic Susceptibilitymentioning

confidence: 99%

Molecular detection of CF lung pathogens: Current status and future potential

Pattison

Rogers

Crockard

et al. 2013

Journal of Cystic Fibrosis

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Molecular diagnostic tests, based on the detection and identification of nucleic acids in human biological samples, are increasingly employed in the diagnosis of infectious diseases and may be of future benefit to CF microbiology services. Our growing understanding of the complex polymicrobial nature of CF airway infection has highlighted current and likely future shortcomings in standard diagnostic practices. Failure to detect fastidious or slow growing microbes and misidentification of newly emerging pathogens could potentially be addressed using culture-independent molecular technologies with high target specificity. This review considers existing molecular diagnostic tests in the context of the key requirements for an envisaged CF microbiology focussed assay. The issues of assay speed, throughput, detection of multiple pathogens, data interpretation and antimicrobial susceptibility testing are discussed.

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Antimicrobial susceptibility and synergy studies of cystic fibrosis sputum by direct sputum sensitivity testing

Cited by 11 publications

References 20 publications

Effect of Media Modified To Mimic Cystic Fibrosis Sputum on the Susceptibility of Aspergillus fumigatus, and the Frequency of Resistance at One Center

Effect of Media Modified To Mimic Cystic Fibrosis Sputum on the Susceptibility of Aspergillus fumigatus, and the Frequency of Resistance at One Center

Impact of High Diversity of Achromobacter Populations within Cystic Fibrosis Sputum Samples on Antimicrobial Susceptibility Testing

Molecular detection of CF lung pathogens: Current status and future potential

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