Guillain-Barré syndrome following primary cytomegalovirus infection: a prospective cohort study.

BACKGROUND: Little is known about the epidemiology and the prognostic factors of Guillain-Barré syndrome (GBS) following primary infection with cytomegalovirus (CMV-GBS). METHODS: We prospectively followed up 506 patients with cases of GBS who were admitted to our center from 1996 through 2006. We diagnosed 63 (12.4%) CMV-GBS cases by immunoglobulin (Ig) M detection and IgG avidity. Plasma CMV DNA was detected at hospital admission. Patient subgroups were compared using Fisher's exact test and the Wilcoxon rank-sum test. Temporal variations were analyzed with time series methods. RESULTS: Patients with CMV-GBS were mostly young (median age, 32 years; sex ratio, 0.85), but we also identified a subpopulation of patients consisting of women aged >50 years. Sensory defects (in 72% of cases) and facial palsy (49%) were frequent, and test results positive for CMV DNA in plasma at hospital admission (found in 62% of cases) tended to be associated with objective sensory defect (P=.052). The main factors associated with long-term neurological sequelae (21%) were older age (P<.001) and assisted ventilation during hospitalization (P=.005). The number of CMV-GBS cases decreased between 1996 and 2006 (P=.019) and displayed an annual periodicity between the months of July and October. The incidence of CMV-GBS was estimated to be between 0.6 and 2.2 cases per 1000 cases of primary CMV infection (versus 0.25 to 0.65 cases per 1000 cases of Campylobacter jejuni infection). CONCLUSIONS: This study provides new insights about the epidemiology of CMV-GBS and shows that the risk of developing GBS is similar following primary CMV infection or C. jejuni infection. Our results also suggest a direct or indirect involvement of viral replication in the neuropathological processes of CMV-GBS.

Decreased susceptibility to teicoplanin and vancomycin in coagulase-negative Staphylococci isolated from orthopedic-device-associated infections.

We studied 315 coagulase-negative Staphylococcus strains recovered prospectively during 240 surgical procedures (206 subjects) from proven or suspected device-associated bone and joint infections. Sixteen strains (5.1%) had decreased susceptibility to glycopeptides: 15 (12 S. epidermidis strains, 2 S. capitis strains, and 1 S. haemolyticus strain) to teicoplanin alone (MIC of 16 mg/liter, n = 9; MIC of 32 mg/liter, n = 6) and one (S. epidermidis) to both teicoplanin and vancomycin (MIC, 16 and 8 mg/liter, respectively). Decreased susceptibility to teicoplanin was more prevalent in "infecting" strains (i.e., strains recovered from >/=2 distinct intraoperative samples) than in "contaminants" (i.e., strains not fulfilling this criterion) (8.1% [12/149] versus 2.4% [4/166], respectively [P = 0.022]). One hundred percent (13/13) of S. epidermidis strains with decreased susceptibility to teicoplanin were resistant to methicillin (versus 112/173 [64.7%] for S. epidermidis strains susceptible to teicoplanin; P = 0.021).

Novel mechanism of resistance to glycopeptide antibiotics in Enterococcus faecium.

Glycopeptides and beta-lactams are the major antibiotics available for the treatment of infections due to Gram-positive bacteria. Emergence of cross-resistance to these drugs by a single mechanism has been considered as unlikely because they inhibit peptidoglycan polymerization by different mechanisms. The glycopeptides bind to the peptidyl-D-Ala(4)-D-Ala(5) extremity of peptidoglycan precursors and block by steric hindrance the essential glycosyltransferase and D,D-transpeptidase activities of the penicillin-binding proteins (PBPs). The beta-lactams are structural analogues of D-Ala(4)-D-Ala(5) and act as suicide substrates of the D,D-transpeptidase module of the PBPs. Here we have shown that bypass of the PBPs by the recently described beta-lactam-insensitive L,D-transpeptidase from Enterococcus faecium (Ldt(fm)) can lead to high level resistance to glycopeptides and beta-lactams. Cross-resistance was selected by glycopeptides alone or serially by beta-lactams and glycopeptides. In the corresponding mutants, UDP-MurNAc-pentapeptide was extensively converted to UDP-MurNAc-tetrapeptide following hydrolysis of D-Ala(5), thereby providing the substrate of Ldt(fm). Complete elimination of D-Ala(5), a residue essential for glycopeptide binding, was possible because Ldt(fm) uses the energy of the L-Lys(3)-D-Ala(4) peptide bond for cross-link formation in contrast to PBPs, which use the energy of the D-Ala(4)-D-Ala(5) bond. This novel mechanism of glycopeptide resistance was unrelated to the previously identified replacement of D-Ala(5) by D-Ser or D-lactate.