Healthcare-associated Gram-negative bloodstream infections: antibiotic resistance and predictors of mortality.

This article describes the prevalence of antibiotic resistance and predictors of mortality for healthcare-associated (HA) Gram-negative bloodstream infections (GN-BSI). In total, 831 cases of HA GN-BSI from 17 intensive care units in different centres in Turkey were included; the all-cause mortality rate was 44%. Carbapenem resistance in Klebsiella pneumoniae was 38%, and the colistin resistance rate was 6%. Multi-variate analysis showed that age >70 years [odds ratio (OR) 2, 95% confidence interval (CI) 1.22-3.51], central venous catheter use (OR 2.1, 95% CI 1.09-4.07), ventilator-associated pneumonia (OR 1.9, 95% CI 1.1-3.16), carbapenem resistance (OR 1.8, 95% CI 1.11-2.95) and APACHE II score (OR 1.1, 95% CI 1.07-1.13) were significantly associated with mortality.

Muscarinic receptor-mediated nitric oxide release in a K562 erythroleukaemia cell line.

1 In the present study we have investigated the expression of muscarinic receptors in K562 erythroleukaemic cells and the effects of muscarinic agonist and antagonists on extracellular citrulline levels in these cells, as a marker of nitric oxide (NO) generation. 2 Muscarinic acetylcholine receptors (M(1)-M(5)) play key roles in regulating many diverse physiological processes. Recent studies suggest that muscarinic receptors mediate some cellular events in haematopoietic cells. Multiple subtypes of muscarinic receptors are expressed in different human cells. NO, a free radical and a signaling molecule, is involved in the regulation of many physiological functions and derived from certain nitric oxide synthases (NOS), which are related to muscarinic receptors. 3 In this study, the presence of M(2), M(3) and M(4) subtypes in K562, an erythroleukaemic cell line, was demonstrated by using the reverse transcriptase-polymerase chain reaction. Moreover, the generation of NO induced by carbachol, a non-selective muscarinic agonist, was investigated by using high-performance liquid chromatography to measure changes in extracellular l-citrulline levels. 4 We found that carbachol enhanced l-citrulline production in K562 erythroleukaemic cells. The effect of carbachol on l-citrulline production was antagonized by atropine and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), while tropicamide had little effect. These results suggest that the muscarinic receptor M(3) subtype may mediate NO signaling in K562 erythroleukaemic cells.

In vitro activity of tigecycline, tetracycline and fluoroquinolones against Brucella melitensis.

Brucellosis is a major zoonotic disease of global importance. Forty years after active drug therapy was defined, there is no optimum antibiotic therapy for brucellosis due to relatively high rates of relapse and treatment failure. The aim of this study was to assess the in vitro susceptibility of 60 Brucella melitensis isolates obtained from blood and fluids to tigecycline, tetracycline and three quinolones (ciprofloxacin, levofloxacin, moxifloxacin). The minimum inhibitory concentrations (MICs) of these antibiotics were determined by E-test method. According to the MIC90, levofloxacin (MIC90 0.094 microg/mL) was found to be the most active agent, followed by tigecycline (MIC90 0.125 microg/mL), moxifloxacin (MIC90 0.125 microg/mL), ciprofloxacin (MIC 90 0.19 microg/mL) and tetracycline (MIC90 0.25 microg/mL). The results suggest that tigecycline can be a therapeutic alternative option for the treatment of brucellosis.

Pulmonary nocardiosis in a non-Hodgkin's lymphoma patient.

Nocardiosis is an opportunistic infection especially in immunocompromised patients. Lungs are the most common infection sites and therapy poses some difficulties. We describe a case of pulmonary infection with Nocardia asteroides in a non-Hodgkin's lymphoma patient. Although the mortality from pulmonary nocardiosis is high in immunocompromised patients, our patient was successfully treated with trimethoprim-sulfamethoxazole (TMP/SMZ) and amikacin. Maintenance therapy with TMP/SMZ was continued for 1 year. This case supports the importance of the long-term maintenance treatment after the initial combination therapy.

Evidence for the presence of muscarinic M2 and M4 receptors in guinea-pig gallbladder smooth muscle.

1. The affinities of 10 selective muscarinic receptor antagonists against [3H]-quinuclidinyl benzilate (QNB) binding were determined to characterize the muscarinic receptors present in guinea-pig gallbladder smooth muscle. The highest correlation was obtained for the comparison between the pKi values for the gallbladder smooth muscle and M2 sites. Pirenzepine revealed two binding sites with affinities indicating the presence of muscarinic M2 receptors in abundance and a minor population of an additional site(s). 2. Carbachol produced gallbladder contractions, stimulated phosphoinositide (PI) hydrolysis and inhibited cAMP formation concentration-dependently with pD2 values of 6.12 +/- 0.11, 5.18 +/- 0.33 and 7.19 +/- 0.15, respectively. 3. Pirenzepine, 4-DAMP, HHSiD, pF-HHSiD, AF-DX 116, methoctramine, AQ-RA 741, guanylpirenzepine and AF-DX 384 showed competitive antagonism against carbachol-induced gallbladder contractions. There was no correlation between the pA2 values for the gallbladder and pKi values for the M2 sites, whereas significant correlations were found for the M1, M3 and M4 sites, the best correlation being between the pA2 values for the gallbladder and M4 subtypes. 4. Finally, the presence of both m2 and m4 receptor proteins were demonstrated by Western blot analysis. It is concluded that guinea-pig gallbladder smooth muscle has both muscarinic M2 and M4 receptors, which are coupled to adenylate cyclase inhibition and PI hydrolysis. 5. Although it seems likely that M2 receptors do not play a primary role in carbachol-induced guinea-pig gallbladder contraction, the characterization of the muscarinic subtypes which mediate these contractile responses needs further evidence.