Pharmacokinetic parameters of CAZ-AVI in the normal lung and in models of pneumonia: lessons for treatment optimization in critical care.

The spread of multidrug-resistant Gram-negative bacterial infections is a significant issue for worldwide public health. Gram-negative organisms regularly develop resistance to antibiotics, especially to ß-lactam antimicrobials, which can drastically restrict the number of therapies. A third-generation cephalosporin and the non-ß-lactam ß-lactamase inhibitor avibactam, which exhibits broad-spectrum ß-lactamase inhibition in vitro, are combined to form ceftazidime-avibactam (CAZ-AVI). In this narrative review, we summarize data on pharmacokinetic (PK) parameters for CAZ-AVI in both animal and human models of pneumonia, as well as in healthy individuals. We assessed current literature performing an extensive search of the literature, using as search words 'CAZ-AVI', 'pharmacokinetics', 'pneumonia', 'lung', and 'epithelial lining fluid'. Overall, lung exposure studies of CAZ-AVI revealed that the epithelial lining fluid penetration ranges between 30% and 35% of plasma concentration. Despite the fair lung penetration of CAZ-AVI, this antimicrobial agent has a pivotal role in managing patients with multi-drug resistant Gram-negative pneumonia, however further studies are needed to better assess its PK profile.

Diagnosis and treatment of pneumonia, a common cause of respiratory failure in patients with neuromuscular disorders.

Patients with neuromuscular diseases, during their illness are more susceptible to respiratory infections due to predisposing factors. Ineffective cough and the presence of atelectasis and hypoventilation, dysphagia and drooling can represent risk factors for the development of respiratory infection and fatal respiratory failure. Infections of respiratory tract with acute respiratory failure are the most common reason for hospitalizations, and pneumonia is among the leading causes of morbidity and mortality worldwide. The setting in which pneumonia is acquired heavily influences diagnostic and therapeutic choices. We will focus on aetiopathogenesis, diagnosis and treatment of pneumonia in these subjects, particularly considering the disease severity, rates of antibiotic resistance and the possible complications. In this case consultations with specialized physicians are strongly recommended.

Combined use of high doses of vasopressin and corticosteroids in a patient with Crohn's disease with refractory septic shock after intestinal perforation: a case report.

BACKGROUND: In this article, we present a clinical case of refractory septic shock resulting from intestinal perforation treated with high doses of vasopressin and hydrocortisone during emergency surgery. The use of such high doses of vasopressin for this type of shock is not described in the literature. CASE PRESENTATION: A 49-year-old white woman with grade III obesity, Crohn's disease, and an intestinal perforation presented with refractory septic shock. Initially, a low dose of vasopressin was used. Then, the dosage was increased to 0.4 U/minute; in the literature, this is defined as "salvage therapy." This therapy consists of an initial load followed by a continuous infusion of hydrocortisone. CONCLUSIONS: The significant increase in her cardiac index and stroke volume index resulted in an improvement in peripheral resistance, gas exchange, and urine output and a decrease in her heart rate, interleukin-6 level, and tumor necrosis factor-α level. The administration of high doses of vasopressin and corticosteroids was demonstrated to be safe for the immune system, to reduce the systemic inflammatory response, and to have direct cardiovascular effects. Further studies are required to examine the use of vasopressin as an initial vasopressor as well as its use in high dosages and in combination with corticosteroids.