The yellow fluorescent protein (YFP-H) mouse reveals neuroprotection as a novel mechanism underlying chondroitinase ABC-mediated repair after spinal cord injury.

Chondroitinase ABC (ChABC) represents a promising therapeutic strategy for the treatment of spinal cord injury due to its potent effects on restoring function to spinal-injured adult mammals. However, there is limited mechanistic insight as to the underlying effects of ChABC treatment, where the effects are mediated, and which signaling pathways are involved in ChABC-mediated repair. Here we use a transgenic (YFP-H) mouse to demonstrate that cortical layer V projection neurons undergo severe atrophy 4 weeks after thoracic dorsal column injury and that ChABC is neuroprotective for these neurons after ICV infusion. ChABC also prevented cell atrophy after localized delivery to the spinal cord, suggesting a possible retrograde neuroprotective effect mediated at the injury site. Furthermore, neuroprotection of corticospinal cell somata coincided with increased axonal sprouting in the spinal cord. In addition, Western blot analysis of a number of kinases important in survival and growth signaling revealed a significant increase in phosphorylated ERK1 at the spinal injury site after in vivo ChABC treatment, indicating that activated ERK may play a role in downstream repair processes after ChABC treatment. Total forms of PKC and AKT were also elevated, indicating that modification of the glial scar by ChABC promotes long-lasting signaling changes at the lesion site. Thus, using the YFP-H mouse as a novel tool to study degenerative changes and repair after spinal cord injury we demonstrate, for the first time, that ChABC treatment regulates multiple signaling cascades at the injury site and exerts protective effects on axotomized corticospinal projection neurons.

Treatment and outcome of Staphylococcus aureus bacteremia: a prospective study of 278 cases.

BACKGROUND: Staphylococcus aureus bacteremia is still a serious problem, and the optimal treatment is under debate. Only a few studies concerning treatment are available. METHODS: The study population was all patients with a positive blood culture result for S aureus in Copenhagen County, Denmark, from May 1994 through April 1996. Of 278 patients with S aureus bacteremia, 186 were evaluated according to outcome in a prospective, observational follow-up study. The time above the minimum inhibitory concentration was estimated for dicloxacillin sodium for each treatment regimen and evaluated by logistic regression along with other potential risk factors. RESULTS: The following variables were statistically associated with death: the presence of an uneradicated focus (odds ratio [OR], 6.7; 95% confidence interval [CI], 2.1-21.0); the presence of septic shock (OR, 3.7; 95% CI, 1.5-9.1); the total daily dose of penicillinase-stable penicillin less than 4 g (OR, 3.7; 95% CI, 1.3-11.1); and age 60 years or older (OR, 2.4; 95% CI, 1.1-5.3). The following variables were significantly associated with recurrence: the total daily dose of penicillinase-stable penicillin less than 3 g (OR, 3.9; 95% CI, 1.6-10.0) and the presence of a secondary focus (OR, 3.2; 95% CI, 1.3-7.7). Among 155 patients with observation time longer than duration of treatment, this factor (duration of treatment, <14 days) was significantly related to mortality (OR, 0.84; 95% CI, 0.76-0.94). CONCLUSIONS: Focus eradication and the dosing of penicillinase-stable penicillin are important to the outcome of S aureus bacteremia. We recommend treatment with at least 1 g of penicillinase-stable penicillins 4 times daily for longer than 14 days.

[Current microbiological problems. Antibiotic resistance and therapeutic problems raised by Pseudomonas aeruginosa]. / Problèmes microbiologiques d'actualité. Résistance aux antibiotiques et problèmes thérapeutiques posés par Pseudomonas aeruginosa.

RESISTANCE: Pseudomonas aeruginosa is characterized by its low intrinsic susceptibility to many antibiotics and its capacity to acquire additional resistance mechanisms to usually active drugs. Some beta-lactam resistance mechanisms are well known (penicillinase production, cephalosporinase overproduction) and others have been recently identified, such as active efflux systems, which confer coresistance to quinolones, and new beta-lactamases which are limited to a few countries (extended-spectrum beta-lactamases, imipenemase). Ceftazidime remains the most active beta-lactam agent. ACTIVE DRUGS: Among aminoglycosides, amikacin and isepamicin are the most frequently active drugs. The use of fluoroquinolones is limited by a high incidence of acquired resistance. The percentage of resistant strains is highly variable according to countries, hospitals and wards. CLINICAL PRACTICE: Therapy, usually based on a beta-lactam-aminoglycoside combination, will be empirical at first, according to local epidemiological factors, site of infection and previously administered antibiotics, then re-evaluated according to susceptibility results.

Celulitis periestomal por Magnusiomyces capitatus en una paciente portadora de gastrostomía percutánea / Peristomal cellulitis due to Magnusiomyces capitatus in a woman carrying percutaneous gastrostomy tube

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Monoterapia vs. terapia combinada en el tratamiento de las infecciones por bacterias gramnegativas multirresistentes / Monotherapy vs. combined therapy in the treatment of multi-drug resistance gramnegative bacteria

El progresivo aumento de las bacterias gramnegativas multirresistentes, especialmente en personas con factores de riesgo, pero también en otras que sufren infecciones comunitarias, hace cada vez más difícil elegir una terapia antibiótica adecuada. Los mayores problemas los generan las bacterias productoras de β-lactamasas de espectro extendido (BLEE) y las productoras de carbapenemasas. Se discutirá en esta mini-revisión la conveniencia de administrar un carbapémico en los casos sospechosos de infección por BLEE que luego se puede modificar según CMI en el antibiograma y una combinación de antibióticos en los casos de infección por gérmenes productores de carbapenemasas, siendo especialmente importante que la combinación incluya un carbapémico y/o colistina a dosis altas (AU)

The increasing number of multidrug resistant gram negative bacteria, particularly in patients with risk factors, but in those who suffer community infections as well, is doing more and more difficult to choose the appropriate treatment. The most challenging cases are due to the production of extended-spectrum-β-lactamases (ESBL) and carbapenemases. This mini-review will discuss the adequacy of administering carbapenems when suspecting infections due to ESBL that could be modified after knowing the MIC of the isolated bacteria and the combined therapy in cases of carbapenemases, being particularly important to include a carbapenem and/or colistine at high dosages in this combination (AU)

Aproximación terapéutica empírica a la infección por gramnegativos resistentes. Valor de los factores de riesgo / Resistant gram-negative bacteria. Therapeutic approach and risk factors

La rápida diseminación de las bacterias multirresistentes se ha convertido en una grave amenaza, especialmente en las unidades de cuidados críticos, prolongando la estancia hospitalaria. Las enterobacterias tienen una alta capacidad de adaptación a cualquier medio. Son los plásmidos los que les facilita su expansión. La elección de un tratamiento empírico adecuado para la infección intraabdominal complicada y para la infección urinaria exige el conocimiento de la variabilidad microbiológica intrínseca de cada hospital o unidad de cuidados críticos, así como el origen de la infección, la seguridad o la toxicidad del antibiótico, la interacción con otras fármacos, la pauta de administración y la presencia de factores de riesgo. Los carbapenémicos son el fármaco de elección ante la sospecha de enterobacterias productoras de b-lactamasas de expectro extendido (BLEE). Los nuevos antimicrobianos, ceftazidima-avibactam y ceftolozano-tazobactam, abren nuevos horizontes esperanzadores en el tratamiento de enterobacterias multirresistentes (AU)

The rapid spread of multidrug-resistant bacteria has become a serious threat, especially in critical care units, thereby prolonging the hospital stay. Enterobacteriaceae have a high capacity to adapt to any environment. Plasmids are the reason behind their expansion. The choice of empiric therapy for intra-abdominal or urinary infections requires knowledge of the intrinsic microbiological variability of each hospital or critical care unit, as well as the source of infection, safety or antibiotic toxicity, interaction with other drugs, the dosage regimen and the presence of risk factors. Carbapenems are the drug of choice in the case of suspected infection by ESBL-producing Enterobacteriaceae. The new ceftazidime/avibactam and ceftolozane/tazobactam drugs are opening up promising new horizons in the treatment of multidrug-resistant Enterobacteriaceae (AU)

Eikenella corrodens in hand infections.

Clinical and therapeutic information on 21 patients with hand infection due to Eikenella corrodens is reported. Patients given empiric therapy ineffective against E. corrodens had a high incidence of complications, while proper empiric therapy was associated with good recovery. All hand wounds should be cultured aerobically and anaerobically and empiric antibiotic therapy should include a penicillinase-resistant penicillin or cephalosporin in combination with penicillin G.

Motor and electrical signs of epileptiform activity induced by penicillin in the spinal cords of decapitate cats.

Convulsive activity was induced in functionally decapitate cat preparations by topical and by systemic administration of toxic amounts of penicillin. The paroxysmal movement patterns and the electrographic signs of spinal seizure activity recorded from spinal ventral and dorsal roots and from the dorsal surface of the spinal cord are described. Paroxysms of interictal myoclonic twitching as well as tonic and clonic ictal seizures reminiscent of epileptiform convulsions of intact animals were seen in the absence of descending influences from the brain. Tonic seizures consisted of flexion--extension sequences; co-contraction of antagonistic muscles was the rule. Clonic activity consisted of rhythmic discharges at 4--6/sec, In dorsal roots, electrotonically conducted paroxysmal negative potential shifts as well as antidromically conducted trains of impulses were recorded. Ictal paroxysmal waves of the cord dorsum potential consisted of either biphasic positive--negative sequences or of purely negative waves. Diphenylhydantoin effectively controlled spinal seizures in the absence of a functioning cerebellum. Diphenylthiohydantoin changed the pattern of seizures, suppressing all ictal activity and greatly enhancing the amplitude and frequency of interictal bursts. Three different barbiturates suppressed seizure activity, but diazepam was ineffective, indicating that the site of its clinical anticonvulsant action may be supraspinal. Seizure activity, once induced, continued for up to 18 h. Intravenous administration of penicillinase abolished seizures indicating that their usual persistence is caused by the presence of the drug in the tissue, not by an irreversible biochemical lesion.