Case Commentary: Novel Therapy for Multidrug-Resistant Acinetobacter baumannii Infection

ABSTRACT

Acinetobacter baumannii is a pathogenic bacterium commonly associated with multidrug resistance. In this issue of Antimicrobial Agents and Chemotherapy, a challenging case of ventilator-associated pneumonia is presented in which bacteriophage therapy was used as a last resort treatment in combination with systemic antibiotics. The data are promising, and several key areas are highlighted for future research.

INTRODUCTION

Antimicrobial resistance (AMR) is emerging as a health care crisis that requires solutions now. In 2019, there were more than 2.8 million infections with AMR in the United States (1). Sadly, the number of infections has been steadily growing each year, and it is predicted that over the next 30 years antimicrobial resistance infections will become the number one cause of death (2). Acinetobacter baumannii is a pathogenic bacterium that requires immediate dedication as part of the AMR crisis. A. baumannii is a Gram-negative, aerobic, pleomorphic, nonmotile bacteria and is most commonly implicated in hospital-acquired infections (3). The Center for Disease Control and World Health Organization have labeled A. baumannii as the highest threat level in their ranking system for antibiotic resistant threats (1, 4), based on clinical impact, incidence rate, projections over 10 years, transmissibility, effective antibiotics available, and the barriers for infection prevention. Despite cefiderocol being approved recently by the FDA as a novel siderophore drug used to treat complicated urinary tract infections and hospital-acquired/ventilator-associated pneumonia (5), treatments are still dismal for the complicated cases. Novel and effective therapeutic options are still desperately desired.

In this issue of Antimicrobial Agent and Chemotherapy, Rao et al. present a case report of a patient with significant underlying comorbidities who was admitted to the hospital and developed ventilator-associated pneumonia during the hospital course (6). The sputum sample was positive for multidrug-resistant A. baumannii. Therapeutic options were very limited and the patient did not respond well to initial antibiotic therapy. Cases such as the one presented are particularly difficult, dreaded among all, and not as uncommon as one might believe. As a last resort option, the bacterial isolate was tested against two bacteriophages that were available. With an emergency investigational new drug application approved by the FDA, the patient was started on IV bacteriophage therapy in combination with antibiotic therapy. Subsequently nebulized bacteriophage was added in view of microbiological persistence in repeated sputum cultures. After bacteriophage therapy, along with different antibiotics for more than a month, the patient’s condition improved significantly. He was weaned from mechanical ventilation and was discharged to a long-term rehabilitation facility for continuation of care.

This case sheds light on important questions to be answered before bacteriophage therapy can be widely used in clinical practice. First, systemic antibiotics were used throughout the course of bacteriophage therapy. For example, cefiderocol was part of the treatment but susceptibility testing information was unavailable. The successful patient outcome reported could have been attributed (at least in part) to this novel agent. The role of concurrent antibiotic therapy should be ascertained in appropriately designed studies. Second, an efficient in vitro screening process of different bacteriophages needs to be developed. Ideally the process could be scaled-up and provide clinicians with patient-specific results in a clinically relevant time frame. Finally, dosing and the most appropriate route of administration should be examined for optimal bacteriophage delivery to the site(s) of infection. Nonetheless, bacteriophage therapy is a promising therapeutic option to be further explored. The experience of this case could be potentially extrapolated to other challenging AMR cases.

The views expressed in this article do not necessarily reflect the views of the journal or of ASM.