Ceftazidime/Avibactam in Ventilator-Associated Pneumonia Due to Difficult-to-Treat Non-Fermenter Gram-Negative Bacteria in COVID-19 Patients: A Case Series and Review of the Literature

Abstract

Ventilator-associated pneumonia (VAP) in critically ill patients with COVID-19 represents a very huge global threat due to a higher incidence rate compared to non-COVID-19 patients and almost 50% of the 30-day mortality rate. Pseudomonas aeruginosa was the first pathogen involved but uncommon non-fermenter gram-negative organisms such as Burkholderia cepacea and Stenotrophomonas maltophilia have emerged as other potential etiological causes. Against carbapenem-resistant gram-negative microorganisms, Ceftazidime/avibactam (CZA) is considered a first-line option, even more so in case of a ceftolozane/tazobactam resistance or shortage. The aim of this report was to describe our experience with CZA in a case series of COVID-19 patients hospitalized in the ICU with VAP due to difficult-to-treat (DTT) P. aeruginosa, Burkholderia cepacea, and Stenotrophomonas maltophilia and to compare it with data published in the literature. A total of 23 patients were treated from February 2020 to March 2022: 19/23 (82%) VAPs were caused by Pseudomonas spp. (16/19 DTT), 2 by Burkholderia cepacea, and 6 by Stenotrophomonas maltophilia; 12/23 (52.1%) were polymicrobial. Septic shock was diagnosed in 65.2% of the patients and VAP occurred after a median of 29 days from ICU admission. CZA was prescribed as a combination regimen in 86% of the cases, with either fosfomycin or inhaled amikacin or cotrimoxazole. Microbiological eradication was achieved in 52.3% of the cases and the 30-day overall mortality rate was 14/23 (60.8%). Despite the high mortality of critically ill COVID-19 patients, CZA, especially in combination therapy, could represent a valid treatment option for VAP due to DTT non-fermenter gram-negative bacteria, including uncommon pathogens such as Burkholderia cepacea and Stenotrophomonas maltophilia.

Real-Life Assessment of the Ability of an Ultraviolet C Lamp (SanificaAria 200, Beghelli) to Inactivate Airborne Microorganisms in a Healthcare Environment

“…In fact, we had the chance to identify both Gram-positive and Gram-negative cocci and rods, including staphylococci, Bacillus spp., Enterobacterales, and non-fermentative Gram-negative bacilli. Most of them can be opportunistic pathogens responsible for severe infections, such as respiratory tract and bloodstream infections, mainly in immunocompromised patients or in the presence of invasive medical devices [ 20 , 21 ]. Moreover, in healthcare settings, most of these bacteria show alarming patterns of antimicrobial resistance, with high morbidity and mortality rates and poor therapeutic options [ 22 , 23 ].…”

Population Pharmacokinetic Modeling for Ceftazidime‐Avibactam Renal Dose Adjustments in Pediatric Patients 3 months and Older

“…However, analysis of post hoc predicted exposures for adults from the phase III program showed that in multiple subgroups of patients with markers of severe/critical illness, including APACHE II score > 10, systemic inflammatory response syndrome, bacteremia, fever, and augmented renal CL, approved adult doses achieved joint target attainment > 90% 5 . In addition, several real‐world studies have reported positive outcomes for the recommended ceftazidime‐avibactam doses in critically ill adult patients 33–35 . Our modeling approach and the resulting dose recommendations based on matching exposures for pediatric patients (including renal impairment) with adults suggests that the recommended pediatric doses will also be suitable for critically ill children.…”

“…5 In addition, several real-world studies have reported positive outcomes for the recommended ceftazidime-avibactam doses in critically ill adult patients. [33][34][35] Our modeling approach and the resulting dose recommendations based on matching exposures for pediatric patients (including renal impairment) with adults suggests that the recommended pediatric doses will also be suitable for critically ill children.…”

Antibiotic-Resistant ESKAPE Pathogens and COVID-19: The Pandemic beyond the Pandemic

“…Diverse new agents active against certain CR pathogens, including ceftazidime-avibactam [ 125 ], ceftolozane-tazobactam [ 126 , 127 ], piperacillin-tazobactam [ 128 ], meropenem-vaborbactam [ 129 ], imipenem-relebactam [ 130 ], imipenem-cilastatin-relebactam [ 131 ] are used in clinics. Specifically, plazomicin [ 132 ], eravacycline [ 133 ], and cefiderocol [ 134 ] have been approved for clinical use or are reaching late-stage clinical development [ 135 ].…”