Compassionate use of a novel ß-lactam enhancer-based investigational antibiotic cefepime/zidebactam (WCK 5222) for the treatment of extensively-drug-resistant NDM-expressing Pseudomonas aeruginosa infection in an intra-abdominal infection-induced sepsis patient: a case report.

Infections in critically-ill patients caused by extensively-drug-resistant (XDR)-Pseudomonas aeruginosa are challenging to manage due to paucity of effective treatment options. Cefepime/zidebactam, which is currently in global Phase 3 clinical development (Clinical Trials Identifier: NCT04979806, registered on July 28, 2021) is a novel mechanism of action based ß-lactam/ ß-lactam-enhancer combination with a promising activity against a broad-range of Gram-negative pathogens including XDR P. aeruginosa. We present a case report of an intra-abdominal infection-induced sepsis patient infected with XDR P. aeruginosa and successfully treated with cefepime/zidebactam under compassionate use. The 50 year old female patient with past-history of bariatric surgery and recent elective abdominoplasty and liposuction developed secondary pneumonia and failed a prolonged course of polymyxins. The organism repeatedly isolated from the patient was a New-Delhi metallo ß-lactamase-producing XDR P. aeruginosa resistant to ceftazidime/avibactam, imipenem/relebactam and ceftolozane/tazobactam, susceptible only to cefepime/zidebactam. As polymyxins failed to rescue the patient, cefepime/zidebactam was administered under compassionate grounds leading to discharge of patient in stable condition. The present case highlights the prevailing precarious scenario of antimicrobial resistance and the need for novel antibiotics to tackle infections caused by XDR phenotype pathogens.

A case series of melioidosis: An underdiagnosed infection.

Melioidosis is an infection caused by Burkholderia pseudomallei. It is a non notifiable disease and is not included in Integrated Disease Surveillance Program by National Center of Disease Control. India is predicted to have highest burden of disease with an estimated mortality of 32,000 per year. Melioidosis presents with a wide range of clinical manifestations like pneumonia, liver and splenic abscess, septicemia etc. This wide spectrum of presentation and mimicry with other infections leads to its misdiagnosis or underdiagnosis. The only source of disease burden in India is few case reports and the true burden and distribution of disease still needs to be assessed. We, hereby, report a case series of four cases aged 28 years, 53 years, 33 years and 22 years. All cases had different clinical presentation ranging from abdominal wall abscess to septicemia and neurological manifestations making the diagnosis challenging. Three of the four cases were discharged after complete recovery while one case went leave against medical advice. To our knowledge this is the first series describing complete recovery of three out of four cases. This case series will help the physicians to raise their index of clinical suspicion of melioidosis in high risk patients presenting with various findings thus improving the chances of correct diagnosis and treatment.

A Comparative Study of Midazolam Alone or in Combination with Dexmedetomidine or Clonidine for Awake Fiberoptic Intubation.

BACKGROUND: Awake fiberoptic intubation (AFOI) is the gold standard technique for managing patients with anticipated difficult airway. Conscious sedation is desirable, not only to make the procedure more tolerable and comfortable for the patient but also to ensure optimal intubating conditions. Ideal sedation regime for AFOI should provide comfort, cooperation, hemodynamic stability, and amnesia along with maintenance of spontaneous respiration. Several sedative agents have been assessed over the past two decades for this purpose but α2 agonists appear to be the favorable choice owing to its sedative, analgesic, amnestic, and sympatholytic properties along with good hemodynamic profile. AIMS: The present study has been aimed to recognize the characteristics of dexmedetomidine, clonidine, and midazolam and to compare their efficacy in providing optimal intubating conditions as well as hemodynamic stability during AFOI. SETTINGS AND DESIGN: A prospective double-blind randomized study done in tertiary care hospital. MATERIALS AND METHODS: Sixty patients of American Society of Anesthesiologists physical status Classes I and II aged 18-60 years with anticipated difficult airway were randomly allocated into three groups. All the patients received injection midazolam bolus followed by sedation infusion of midazolam, dexmedetomidine, and clonidine according to the allocated group. Primary outcome includes the time to achieve Ramsay Sedation Score (RSS) ≥2, time taken in intubation, intubation score, comfort score for fiberoptic insertion and intubation, and patient tolerance after intubation. The secondary outcome was hemodynamic, and respiratory variables include changes in heart rate (HR), mean arterial pressure (MAP), oxygen saturation (SpO2), and respiratory rate during the procedure. STATISTICAL ANALYSIS: All data were recorded, summarized, tabulated, and statistically analyzed using SPSS 16.0 version (Chicago, Inc., USA). The data were presented in mean ± standard deviation. P < 0.05 was considered as statistically significant. RESULTS: All the three groups were comparable in terms of demographic profile. Time to achieve RSS ≥2 and mean intubation time was significantly less in Groups D and C as compared to Group M (P < 0.001). Among groups, Group D took least time to achieve RSS ≥2 (5.53 ± 0.74) and mean intubation time (4.53 ± 0.91). Similarly, overall intubation score, comfort, and patient tolerance score were significantly more in Group M as compared to Groups D and C (P < 0.001). Among the groups, Group D achieved least intubation score (3.80 ± 0.67) and comfort score (2.53 ± 0.74). Although Groups D and C have a lower mean HR and MAP during the procedure and intubation compared to Group M, the incidence of SpO2 is most frequent with clonidine. CONCLUSIONS: Patients who received α2 agonist were calmer and cooperative with less pain and discomfort than the patients who received midazolam. Dexmedetomidine allows better endurance, stable hemodynamics, and patent airway as compared to clonidine.

Management of traumatic flail chest in intensive care unit: An experience from trauma center ICU.

BACKGROUND/AIM: The thoracic injury and related complications are responsible for upto 25% of blunt trauma mortality. This study is designed to compare these two popular ventilation modes in traumatic flail chest. MATERIALS AND METHOD: A total of 30 patients with thoracic trauma, aged 18-60 years, were enrolled in this study for a period of 1 year. The Thoracic Trauma Severity Score (TTSS) was used for assessing the severity of chest injury. Patients were divided into two treatment groups: one recieved endotracheal intubation with mechanical ventilation (ET group, n = 15) and another recieved noninvasive ventilation (NIV group, n = 15). All patients were observed for the duration of ventilatory days, complications such as pneumonia and sepsis, length of the stay in ICU, and mortality. Statistical analysis was done using statistical software SPSS for windows (Version 16.0). RESULTS: There were no significant differences in age, sex, weight, and length of the stay in ICU in between the two groups. Rate of complications was significantly higher in ET group. Oxygenation was significantly improved in NIV group within 24 hr, later it become equivalent to the ET group patients while the pCO2 level was significantly lower in ET group compared with NIV group. Analgesia in both the groups is maintained to keep the visual analog scale (VAS) score below 2 and was comparable in both the groups. CONCLUSIONS: The endotracheal intubation is also associated with serious complications as compared to NIV. The use of NIV in appropriate patients decreases complications, mortality, length of the stay in ICU, the use of resources, and cost.