Activity of imipenem against VIM-1 metallo-beta-lactamase-producing Klebsiella pneumoniae in the murine thigh infection model.

The in-vivo activity of imipenem against VIM-1-producing Klebsiella pneumoniae (VPKP) was assessed in a thigh infection model in neutropenic mice. Animals were infected with three VPKP isolates (imipenem MICs 2, 4 and 32 mg/L, respectively) and a susceptible clinical isolate (MIC 0.125 mg/L) that did not produce any beta-lactamase with broad-spectrum activity. Bacterial density at the site of infection was determined after imipenem treatment (30 and 60 mg/kg every 2 h for 24 h). The log(10) reduction in CFU/thigh was greatest for the wild-type isolate, intermediate for the two imipenem-susceptible VPKP isolates, and lowest for the imipenem-resistant VPKP isolate. Whilst in-vivo imipenem activity appeared reduced against in-vitro susceptible VIM-1 producers compared with a VIM-1-negative control, an increased drug dosage could moderate this reduction.

["Continuum" and "Spectrum" hypotheses of depressive disorders].

Nowadays, the acceptance of depressive disorders as distinct entities in a categorical system with clearly defined diagnostic criteria has been considered by many researchers to be dysfunctional and stringent. An increasing number of patients with mild depressive symptomatology and dysfunction, who do not satisfy specific diagnostic criteria, seek help in primary care settings. Many questions arise in relation to whether contemporary categories of depressive disorders categories adequately reflect the broad spectrum of depressive disorders occurring in the general population. Contemporary classification-categorization systems are based on the development of diagnostic categories using a "threshold" that defines the subjective dimensional depressive spectrum. However, the so-called categorical or "threshold" diagnostic system of depressive disorders is nowadays open to skepticism. According to the "continuum" hypothesis, depressive disorders extend from normality up to exceptionally disturbed symptomatology (i.e. major depression) and behaviour (i.e. suicidality). Moreover, the "spectrum" of depressive disorders includes a variety of signs and symptoms, extending from the core depressive symptoms to temperament characteristics. These symptoms and/or signs could manifest during a depressive episode, between depressive episodes, or even in the absence of depressive episodes. Many researchers argue that subthreshold (subsyndromal) depressive symptoms may be prodromal or residual manifestations of depressive episodes, or may represent early stages of the continuum of major depressive disorders. The continuum and the spectrum hypotheses of depression could be especially beneficial to the development of primary care prevention programms. However, various concerns have been expressed in relation to the depressive continuum and spectrum hypotheses. Such arguments include the decrease of the reliability and validity of the depression diagnosis, as well as the need for introduction of new subgroup categories of depressive disorders, based on special symptoms (i.e. typical or atypical depression). The lack of specific psychometric instruments measuring subthreshold symptoms should also be considered. The above hypotheses of depressive disorders require further theoretical elaboration and confirmation by systematic research studies.