Beta-lactam and macrolide resistance and serotype distribution among Streptococcus pneumoniae isolates from Saudi Arabia.

Three hundred thirty-six clinically significant Streptococcus pneumoniae isolates were collected from laboratories of different hospitals in Riyadh, Saudi Arabia. Most of these isolates were from pulmonary and otitis media (68.2%), and 31.8% were extrapulmonary (blood and CSF). Of the 336 isolates, 44.6% were susceptible to penicillin, and 55.4% were penicillin non-susceptible (35.7% were intermediate and 19.7% were fully resistant). The isolates showed 9.0% resistance to co-amoxiclav, 31.8% to cefuroxime and 39.4% to cefprozil. None of the isolates were resistant to ceftriaxone. Overall macrolide resistance rates were 22.6% to erythromycin, 18.5% to roxithromycin, 17.9% to azithromycin and 17.3% to clarithromycin. Most penicillin non-susceptible pneumococci were of serogroups/types 19 (21.0%), 6 (10.8%), 18 (8.6%), 23 (8.1%) and 14 (7.0%). Serogroups 9, 15, and 1 were found in 5.4%, 4.3%, and 2.2% of the isolates, respectively. Nontypeable strains constituted 6.5%. In exploring the mechanism of resistance to macrolides, 28 of 76 (36.8%) of isolates were erythromycin-resistant due to ribosomal mechanism (all were constitutive type, none were inducible), whereas 48 (63.2%) isolates were resistant due to an efflux mechanism. Good antibiotic control with periodical antibiotic surveillance and appropriate use of pneumococcal vaccine may improve current treatment of pneumococcal infections.

Effect of lipopolysaccharide on mitogen-activated protein kinases and cytosolic phospholipase A2.

The addition of platelet-activating factor (PAF) to human neutrophils increases phosphorylation on tyrosine residues and stimulates the activity of p42erk2 mitogen-activated protein kinase (MAP kinase). This action is rapid and transient. In contrast, p42erk2, p44erk1 and the p40hera MAP kinase isoforms are all not tyrosine phosphorylated or activated in human neutrophils stimulated with low concentrations of lipopolysaccharide (LPS) in combination with serum. In spite of this, the PAF-induced tyrosine phosphorylation and activation of the p42erk2 MAP kinase are greatly potentiated in cells pretreated with LPS. More interestingly, although low concentrations of LPS do not affect MAP kinase isoforms in these cells, they cause the phosphorylation of cytosolic phospholipase A2 (cPLA2), as evidenced by a decrease in the electrophoretic mobility of the enzyme. In addition, this stimulus-induced upward shift in the mobility of the enzyme is not inhibited by the tyrosine kinase inhibitor, genistein. Furthermore, LPS increases the release of arachidonic acid in control and PAF-stimulated human neutrophils. These observations clearly show that cPLA2 can be phosphorylated and activated by kinases other than the currently known MAP kinases. It is proposed that there are MAP kinase-dependent and -independent mechanisms for the phosphorylation of cPLA2.