Darren Wong

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

SUMMARY Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organisms environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)–Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

Novel Beta-Lactamase Inhibitors: Unlocking Their Potential in Therapy

Carbapenem-resistant Enterobacteriaceae are amongst the most feared pathogens due to severely limited treatment options. In response to this threat, three novel β-lactamase inhibitors have been developed in an attempt to reinvigorate and sustain our current antimicrobial therapies. Avibactam, vaborbactam, and relebactam are inhibitor agents with high affinity to Ambler class A and C β-lactamases and favorable outcomes in current clinical trials. However, although they do possess key similarities, these agents have unique differences which may have important clinical implications. The microbiologic spectrum, pharmacokinetics, and key clinical trials for each of these novel agents are reviewed. A proposed role in therapy and potential novel combinations are examined.

Leveraging antimicrobial stewardship into improving rates of carbapenem-resistant Enterobacteriaceae

ABSTRACT Carbapenem-resistant Enterobacteriaceae (CRE) are among the most critical threats facing our healthcare system and account for significant patient mortality. There is considerable interest in the development of new treatment strategies. However, less attention has been paid to reducing CRE infection rates. Antibiotic stewardship programs can be uniquely empowered to reduce widespread pathogen resistance and by extension, optimize patient care and lower healthcare costs.

Facklamia species as an under-recognized pathogen

Abstract Facklamia species are a rarely reported etiology of clinical infection with few cases described in literature. However, the prevalence of infection may be underestimated due to challenges in species identification. We describe 3 cases of Facklamia species bacteremia and the unique microbiologic aspects inherent to this genus that make it particularly challenging to identify. In addition, given the unique susceptibility profile of Facklamia species, we discuss the importance of fully identifying this organism when it is a suspected as a pathogen, to optimize therapy based on its distinct antibiotic resistance profile.

A case of liver abscess and fusobacterium septicemia

Fusobacterium species are well described as the causative pathogen in Lemierre’s syndrome, a suppurative thrombophlebitis of the jugular vein. However, they are less recognized for a unique variant of Lemierre’s syndrome presenting with invasive intraabdominal infection and associated portal vein thrombosis. We describe a case of Fusobacterium nucleatum with hepatic abscess and septic pylephlebitis.

Anti-NMDAR encephalitis, a mimicker of acute infectious encephalitis and a review of the literature

Anti-N-methyl-d-aspartate receptor encephalitis has become an increasingly recognized etiology of acute psychosis in young patients. The diverse constellation of symptoms allows for misdiagnosis as an infectious, psychological, or toxicological entity resulting in delays in treatment with increasing morbidity. We describe a case of anti-NMDAR encephalitis that was a particular challenge to diagnose. Practitioners should maintain a high index of suspicion for anti-NMDAR and related neuroautoimmune syndromes, especially in young patients that present with acute mental status decline or dyskinesia.

Osteomyelitis Complicating Sacral Pressure Ulcers: Whether or Not to Treat With Antibiotic Therapy

The treatment of osteomyelitis in patients with stage IV sacral pressure ulcers is controversial. We conducted a systematic literature review and did not find evidence of benefit of antibacterial therapy in this setting without concomitant surgical debridement and wound coverage. Furthermore, many patients with chronically exposed bone do not have evidence of osteomyelitis when biopsied, and magnetic resonance imaging may not accurately distinguish osteomyelitis from bone remodeling. The goal of therapy should be local wound care and assessment for the potential of wound closure. If the wound can be closed and osteomyelitis is present on bone biopsy, appropriate antibiotic therapy is reasonable. We find no data to support antibiotic durations of >6 weeks in this setting, and some authors recommend 2 weeks of therapy if the osteomyelitis is limited to cortical bone. If the wound will not be closed, we find no clear evidence supporting a role for antibiotic therapy.