第750回 千葉医学会例会・第2回 磯野外科例会 3.

<div><p>A broad spectrum of symptoms has been associated with <i>C</i>. <i>difficile</i> infection (CDI). Several studies indicate that toxin-production correlates with growth rates of <i>C</i>. <i>difficile</i>. This study aimed to correlate growth rates of <i>C</i>. <i>difficile</i> with disease severity and strain characteristics. From 01/2003 to 10/2011, strains from a prospective cohort of all inpatients with CDI at the University Hospital Basel, Switzerland were analyzed regarding binary toxin, presence of the tcdC deletion and ribotype. Isothermal microcalorimetry was performed to determine growth rates, quantified by the Gompertz function. Ordered logistic regression models were used to correlate disease severity with strain features and clinical characteristics. Among 199 patients, 31 (16%) were infected with binary toxin-producing strains, of which the tcdC gene-deletion nt117 was detected in 9 (4%). Disease severity was classified as mild in 130 patients (65.3%), as severe in 59 patients (29.7%) and as severe/complicated in 10 patients (5.0%). Growth rates were inversely associated with disease severity in univariable (OR 0.514, 95%CI 0.29–0.91, p = 0.023) and multivariable analyses (OR 0.51, 95%CI 0.26–0.97, p = 0.040). While none of the strain characteristics such as presence of the tcdC gene deletion or binary toxin predicted CDI severity, growth rates were inversely correlated with disease severity. Further investigations are needed to analyze growth-regulators and respective correlations with the level of toxin production in <i>C</i>. <i>difficile</i>, which may be important determinants of disease severity.</p></div

Characteristics of patients carrying plasmid-mediated AmpC beta-lactamase- and ESBL-producing Enterobacteriaceae (each 39 patients); univariate logistic regression analysis to define risk factors for plasmid-mediated AmpC beta-lactamase producers.

<p>Abbreviations: pAmpC, plasmid-mediated AmpC beta-lactamase; ESBL, Extended-Spectrum beta-Lactamase; OR, odds ratio; CI, confidence interval; MRE, multidrug-resistant Enterobacteriaceae; eGFR, estimated glomerular filtration rate; COPD, chronic obstructive pulmonary disease</p><p>^* Matching variables</p><p>‡ Patients with known exposure status to antibiotic treatment: 32 in the pAmpC and 33 in the ESBL group</p><p>§ >10 mg prednisone equivalent daily for >3 months</p><p>† McCabe Score: 1 = non-fatal disease (supposed survival >5 years for >50% of patients with the disease), 2 = ultimately fatal disease (supposed survival 1–5 years for >50% of patients with the disease), 3 = rapidly fatal disease (supposed death within 1 year for >50% of patients with the disease)</p><p>Characteristics of patients carrying plasmid-mediated AmpC beta-lactamase- and ESBL-producing Enterobacteriaceae (each 39 patients); univariate logistic regression analysis to define risk factors for plasmid-mediated AmpC beta-lactamase producers.</p

Antimicrobial susceptibility data of plasmid-mediated AmpC beta-lactamase- and ESBL-producing Enterobacteriaceae (each 39 patients).

<p>Abbreviations: pAmpC, plasmidic AmpC beta-lactamase; ESBL, Extended-Spectrum beta-Lactamase; n.a., not available; CLSI, Clinical and Laboratory Standards Institute</p><p>Percentages were calculated using susceptible isolates as nominator and all tested isolates as denominator, which was different for each antibiotic</p><p>* pAmpC producers normally are susceptible to cefepime. In five patients additional ESBL-production was documented partially explaining resistance</p><p>‡ Not available in accordance with the CLSI recommendations during the study period to report ESBL always as non-susceptible to cephalosporins</p><p>§ Susceptibility pattern of the VITEK did not include fosfomycin during the study period, therefore only a part of the isolates was tested (mostly on request by the treating physician)</p><p>Antimicrobial susceptibility data of plasmid-mediated AmpC beta-lactamase- and ESBL-producing Enterobacteriaceae (each 39 patients).</p

Distribution of species and molecular types of plasmid-mediated AmpC beta-lactamase- and ESBL-producing Enterobacteriaceae (each 39 patients).

<p>Abbreviations: pAmpC, plasmid-mediated AmpC beta-lactamase; ESBL, Extended-Spectrum Beta-Lactamase; n.a., not available</p><p>* In one patient both <i>E</i>. <i>coli</i> and <i>K</i>. <i>pneumoniae</i> were isolated; this patient counts only once for the <i>E</i>. <i>coli</i> group</p><p>Distribution of species and molecular types of plasmid-mediated AmpC beta-lactamase- and ESBL-producing Enterobacteriaceae (each 39 patients).</p

PFGE based typing with gel-view and dendrogram.

<p>Dice analysis indicates a very high relatedness in the outbreak-associated cluster. Isolates 21 and 29 are clearly separated.</p

Prevalence of plasmid-mediated AmpC beta-lactamase-producing Enterobacteriaceae from 2006 to 2010.

<p>* Number of positive compared to screened isolates (%)</p><p>Prevalence of plasmid-mediated AmpC beta-lactamase-producing Enterobacteriaceae from 2006 to 2010.</p

MALDI-TOF MS based typing.

<p><b>A. Representative example of mass spectrum differences between ESBL <i>E</i>. <i>coli</i>.</b> Isolates are indicated by color code. Isolates 1, 5, 9, 13, 17 and 25 (outbreak cluster) show a clear distinguished peak at position 4175 m/z, whereas isolates 21 and 29 show a shift to position 4165 m/z (non-related cluster). This corresponds to change of about 10Da. Various other areas of peak shifts have been identified between outbreak and non-related ESBL <i>E</i>. <i>coli</i> clusters. <b>B. MALDI-TOF MS based virtual gel view.</b> MS generated peaks of the protein expression profile are shown for every bacterial isolate. Red labels highlight the non-related isolates. <b>C. Three-dimensional principal component analysis.</b> Based on the Euclidean distance analysis algorithm a three dimensional plot was generated. PC1 and PC2 showed the highest discriminatory potential and indicated a cluster for the outbreak associated isolates, whereas the non-related isolates are less similar. <b>D. PCA-based dendrogram generated by MALDI-TOF MS.</b> The PCA based dendrogram uses a hierarchical clustering algorithm with a Euclidean distance analysis.</p

Associations of strain characteristics with disease severity.

<p>Associations of strain characteristics with disease severity.</p

Comparison of time to treatment failure in different types of prosthetic vascular graft infections.

<p>Infections are compared with respect to the location of the prosthetic vascular graft using Kaplan-Meier estimates.</p

Comparison of primary and secondary outcomes in the treatment of prosthetic vascular graft infection.

<p>PVGI  =  prosthetic vascular graft infection. ^*p-value  = 0.006. ^†p-value  = 0.001. ^‡p-value  = 0.004. ^§p-value  = 0.012. **Removal or replacement of the infected vascular graft. ^††No surgical intervention; antimicrobial treatment only.</p