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 β-lactam/ β-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 β-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.

The emergence of Klebsiella pneumoniae carbapenemases (KPCs) producing bacteria has become a significant global public health challenge while the optimal treatment remains undefined. We performed a systematic review of published studies and reports of treatment outcomes of KPC infections using MEDLINE (2001-2011). Articles or cases were excluded if one of the following was fulfilled: no individual patient data provided, no treatment regimen specified, no treatment outcome specified, report of colonization, or greater than three antibiotics were used to treat the KPC infection. Data extracted included patient demographics, site of infection, organism, KPC subtype, antimicrobial therapy directed at KPC-infection, and treatment outcome. Statistical analysis was performed in an exploratory manner. A total of 38 articles comprising 105 cases were included in the analysis. The majority of infections were due to K. pneumoniae (89%). The most common site of infection was blood (52%), followed by respiratory (30%), and urine (10%). Forty-nine (47%) cases received monotherapy and 56 (53%) cases received combination therapy directed at the KPC-infection. Significantly more treatment failures were seen in cases that received monotherapy compared to cases who received combination therapy (49% vs 25%; p= 0.01). Respiratory infections were associated with higher rates of treatment failure with monotherapy compared to combination therapy (67% vs 29% p= 0.03). Polymyxin monotherapy was associated with higher treatment failure rates compared to polymyxin-based combination therapy (73% vs 29%; p= 0.02); similarly, higher treatment failure rates were seen with carbapenem monotherapy compared to carbapenem-based combination therapy (60% vs 26%; p= 0.03). Overall treatment failure rates were not significantly different in the three most common antibiotic-class combinations: polymyxin plus carbapenem, polymyxin plus tigecycline, polymyxin plus aminoglycoside (30%, 29%, and 25% respectively; p=0.6). In conclusion, combination therapy is recommended for the treatment of KPC infections; however, which combination of antimicrobial agents needs to be established in future prospective clinical trials.

BACKGROUND: Multidrug-resistant strains of Acinetobacter pose a serious therapeutic dilemma in hospital practice, particularly when they cause meningitis, as the few antimicrobial agents to which these isolates are susceptible have poor central nervous system (CNS) penetration.
METHODS: We retrospectively reviewed the clinical course and outcome of eight consecutive cases of meningitis due to Acinetobacter spp. in children ages 15 years or less, seen in a tertiary care medical center in Karachi, Pakistan.
RESULTS: Of the eight cases of Acinetobacter meningitis, isolates from five patients were pan-resistant, and two were multidrug-resistant. A neurosurgical procedure was performed in five of eight patients followed by external ventricular drain insertion prior to the development of infection. Seven received intravenous (IV) polymyxin (mean; 12.8 days), while 5/8 also received intrathecal (IT) polymyxin (mean; 12.0 days). The mean length of hospitalization was 38.7 ± 19 days. All patients achieved cerebrospinal fluid (CSF) culture negativity by the end of treatment (mean; 5.4 days). Two patients died: one with pan-resistant Acinetobacter, and the second with a multi-drug resistant isolate.
CONCLUSIONS: Post-neurosurgical multidrug-resistant and pan-resistant Acinetobacter meningitis can be successfully treated if appropriate antimicrobial therapy is instituted early. The role of IT polymyxin B administration alone versus combination therapy (IV and IT) needs further study.

A 65-year-old man was admitted because of high grade fever and cough after 3 days of gathering edible wild plants. Although ceftriaxone was given to him, his symptoms did not improve. His high grade fever escalated after changing the antibiotics (imipenem with erythromycin). His situation further declined with disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). As a result, he was transferred to the Department of Respiratory Medicine 7 days after admission. He was intubated and placed on mechanical ventilation and treated by polymyxin-direct hemoperfusion. The eschar on his chest wall caused us to suspect Tsutsugamushi disease and a blood test confirmed our suspicion. Since the antibodies for Tsutsugamushi were elevated we arrived at the diagnosis of Tsutsugamushi disease with DIC and ARDS. The administration of tetracycline was sufficient to significantly improve his condition. Because its complications are life threatening, when we see a patient with fever and eruptions, it is necessary to keep in mind the possibility of Tsutsugamushi disease. Careful anamnesis and physical examinations are most important for the diagnosis of Tsutsugamushi disease.

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