In vitro selected fluoroquinolone-resistant mutants of Citrobacter freundii: analysis of the quinolone resistance acquisition

Ten quinolone-resistant mutants of Citrobacter freundii, which were selected in vitro with fluoroquinolones from two clinical isolates, were studied. The parent isolates were susceptible to quinolones in spite of showing a single substitution in the GyrB (His-417 --> Leu). No change was observed in the outer membrane proteins or in the lipopolysaccharide in any of the ten mutants studied with respect to their parent isolates. The development of quinolone resistance in selected mutants was associated with the appearance of a substitution in the GyrA (Thr-83 --> Ile) in nine of the ten mutants plus enhanced active efflux in all of them.     

Decreased production of AmpC-type beta-lactamases associated with the development of resistance to quinolones in Citrobacter freundii strains

The effect of fluoroquinolones in Citrobacter freundii strains that results in a decreased expression of cephalosporin-hydrolysing beta-lactamases was studied. Resistance to broad-spectrum cephalosporins and penicillins in two C. freundii clinical isolates was associated with moderate production of chromosomal AmpC-type-beta-lactamase in addition to changes in the outer membrane proteins profile with respect to wild-type C. freundii strains. Ten quinolone-resistant mutants were derived from the two clinical isolates using increasing fluoroquinolone concentrations. The level of susceptibility to cephalosporins and meropenem of these 10 mutants was increased and was associated with a 3.6-32% diminution in the hydrolyzing activity of their periplasmic extracts containing beta-lactamases on cephaloridine as compared with those from their parent strains. Susceptibility to cephalosporins and meropenem, as well as the expression of chromosomal AmpC-type-beta-lactamase in C. freundii strains, was influenced by the exposure to quinolones.     

Light chain deposition disease restricted to the brain: The first case report

A 35-year-old white male with symptoms of paranoid schizophrenia was treated by psychiatrists for 13 years. During the final year, he developed severe dysphagia, reduced strength of the upper extremity muscles, and cognitive dysfunction. The patient died in his sleep. The only pathology found in coronal brain sections was ill-defined periventricular foci with prominent, firm vessels. Microscopy revealed abundant, hematoxylin and eosin-eosinophilic, periodic acid-Schiff-positive, thioflavin T-positive, and Congo red-negative deposits in the vessel walls, with hypoxic encephalopathy in the affected regions. Immunohistochemistry showed lambda light chains as the main component of the deposits. Ultrastructural analysis showed amorphous electron dense material in the vessel walls. Perivascular B-cell proliferation was present in the vicinity of affected areas. Polymerase chain reaction was applied for the assessment of B-cell clonality, revealing monoclonal rearrangement of the heavy chain Ig gene. Neither in the kidney nor in any other organ were deposits detected. This is the first case report of light chain deposition disease restricted to the brain.