Comparison of basic parameters of excluded and included cases, controls and overall considered patients.

<p>IQR, interquartile range. CCI, Charlson co-morbidity Index. P-value from Chi-square test or^aWilcoxon rank sum test, respectively.</p

Distribution of CTX-M-genotypes in n = 83 CTX-M-positive community-acquired ESBL <i>E. coli</i> isolates.

<p>Distribution of CTX-M-genotypes in n = 83 CTX-M-positive community-acquired ESBL <i>E. coli</i> isolates.</p

Demographic data for included cases colonized with ESBL-positive <i>E. coli</i> and controls without ESBL colonization.

<p>IQR, interquartile range. BMI, Body Mass Index. CCI, Charlson co-morbidity Index. AIDS, acquired immune deficiency syndrome. P-value from Chi-square test or^aWilcoxon rank sum test, respectively.</p

Results of the multivariable conditional logistic regression analysis of risk factors for colonization with ESBL-positive <i>E. coli</i>.

<p>Results of the multivariable conditional logistic regression analysis of risk factors for colonization with ESBL-positive <i>E. coli</i>.</p

Results of the questionnaire based interview: cases colonized with ESBL-positive <i>E. coli</i> and controls without ESBL colonization.

<p>MRSA, Methicillin resistant <i>S.aureus</i>; VRE, Vancomycin resistant <i>Enterococcus.</i> MDRO, multi drug resistant organism. P-value from Chi-square test. East Asia: China, Japan, Mongolia, North Korea, South Korea, Taiwan. West Asia: Bahrain, Iraq, Israel, Yemen, Jordan, Qatar, Kuwait, Lebanon, Oman, Palestine, Saudi Arabia, Syria, Turkey, UAE, Cyprus. South Asia: Afghanistan, Bangladesh, Bhutan, India, Iran, Maldives, Nepal, Pakistan, Sri Lanka.</p

Results of susceptibility testing (MICs), the molecular analyses of β-lactamases and porins, the efflux properties (EHT), and the synergism testing (FICIs).

<p>The EHT and the FICI values are given as median ± standard deviation. Synergistic FICI values are indicated in bold letters. The FICI values indicated in brackets represent the lowest values for the given combination.</p><p>*Strains were obtained from: NRZ = National Reference Laboratory for multidrug-resistant gram-negative bacteria, Ruhr-University Bochum, Germany, and RKI = Robert-Koch-Institut, Wernigerode, Germany; MEM = meropenem; CST = colistin; TCG = tigecycline; FICI = fractional inhibitory concentration index; EHT = efflux half-time; nm = not measureable; aa = amino acid;:: = gene dispuption by insertion sequence; del = deletion; ins insertion; sub = substitution;</p><p>**non-functional (STOP mutation in <i>bla</i>_OXA-9 gene)</p><p>Results of susceptibility testing (MICs), the molecular analyses of β-lactamases and porins, the efflux properties (EHT), and the synergism testing (FICIs).</p

Recruitment diagram of cases and controls.

<p>EHEC, enterohemorrhagic <i>E. coli.</i> ESBL, extendend-spectrum beta-lactamase.</p

Three Dimensional Checkerboard Synergy Analysis of Colistin, Meropenem, Tigecycline against Multidrug-Resistant Clinical <i>Klebsiella pneumonia</i> Isolates

<div><p>The spread of carbapenem-non-susceptible <i>Klebsiella pneumoniae</i> strains bearing different resistance determinants is a rising problem worldwide. Especially infections with KPC (<i>Klebsiella pneumoniae</i> carbapenemase) - producers are associated with high mortality rates due to limited treatment options. Recent clinical studies of KPC-blood stream infections revealed that colistin-based combination therapy with a carbapenem and/or tigecycline was associated with significantly decreased mortality rates when compared to colistin monotherapy. However, it remains unclear if these observations can be transferred to <i>K</i>. <i>pneumoniae</i> harboring other mechanisms of carbapenem resistance. A three-dimensional synergy analysis was performed to evaluate the benefits of a triple combination with meropenem, tigecycline and colistin against 20 <i>K</i>. <i>pneumoniae</i> isolates harboring different β-lactamases. To examine the mechanism behind the clinically observed synergistic effect, efflux properties and outer membrane porin (Omp) genes (<i>ompK35</i> and <i>ompK36</i>) were also analyzed. Synergism was found for colistin-based double combinations for strains exhibiting high minimal inhibition concentrations against all of the three antibiotics. Adding a third antibiotic did not result in further increased synergistic effect in these strains. Antagonism did not occur. These results support the idea that colistin-based double combinations might be sufficient and the most effective combination partner for colistin should be chosen according to its MIC.</p></div

Alignment of representatives of the CTX-M groups.

<p>The IUPAC code was used to highlight the variable nucleotides within the primer sequences and the sequence positions analyzed by pyrosequencing, for the last the code displays the nucleotide variants within the group (for example K in group 1 = G or T). Positions of PCR and sequencing primers (for details see Material and Methods) are framed and the sense and antisense directions are indicated with arrows. The degenerated nucleotides within the primer annealing positions are highlighted in grey.</p

PCR products of various β-lactamases.

<p>The qRT samples were analyzed on a 1.5 % agarose gel after 45 cycles PCR. (A) PCR-products of NP- region 1; Lines: 1, 16= Low-range molecular ladder (Thermo Scientific), 2 = CTX-M-15, 3 = CTX-M-1, 4 = CTX-M-2, 5 = CTX-M-3, 6 = CTX-M-9, 7 = CTX-M-14, 8 = CTX-M-27, 9 = SHV-4, 10 = TEM-1, 11 = OXA-10, 12 = TEM-1, 13 = NTC, 14 = CTX-M-8, 15 = CTX-M-25. (B) PCR-products of NP-region 2; 1, 16 and 19 = Low-range molecular ladder (Thermo Scientific), 2 = 1 pg CTX-M-15, 3 = 10^-1 pg CTX-M-15, 4 = 10^-2 pg CTX-M-15, 5 = 10^-3 pg CTX-M-15, 6 = CTX-M-1, 7 = CTX-M-2, 8 = CTX-M-3, 9 = CTX-M-9, 10 = CTX-M-14, 11 = CTX-M-27, 12 = OXA-1, 13 = OXA-10, 14 = TEM-2, 15 = SHV-4, 17 = CTX-M-8, 18 = CTX-M-25.</p