In the current era of medicine, the creation of practice guidelines and the way we provide care to our patients are based on:
- a combination of data gathered from large cohorts of retrospective observational studies
- Well-conducted randomized clinical trials
- Reliance on our knowledge and understanding of basic scientific principles
- Our individual and collective accumulated experiences.
However, a significant portion of our daily clinical practice remains rooted in dogma, dictum, and tradition1.
In view of this, intravenous vancomycin and Zosyn are commonly used first-line antibiotics in the empiric management of critically ill patients. The role of antibiotics in the treatment of active infections is to eradicate the causative organisms as quickly and efficiently as possible. In fact, according to the Surviving Sepsis Campaign Guidelines, empiric antimicrobial drugs with activity against all likely pathogens should be administered in the first hour of recognition of sepsis or septic shock. Perhaps, this is why providers often use vancomycin and Zosyn.
But what are vancomycin and Zosyn?
Vancomycin is a lipoglycopeptide antibiotic originally isolated from Amycolatopsis orientalis that was first discovered in the 1950s. Vancomycin has a large antimicrobial spectrum that includes Staphylococcus aureus, coagulase-negative Staphylococci, Streptococcus pneumoniae, Streptococcus spp., Enterococcus spp., C. jeikeium, L. monocytogenes, and Actinomyces2.
Zosyn (piperacillin/tazobactam) is a beta-lactam/beta-lactamase inhibitor, which was approved by the US Food and Drug Administration in 1993. Zosyn’s antimicrobial spectrum includes Staphylococcus aureus (methicillin-susceptible), coagulase-negative Staphylococci, Streptococcus pneumoniae, H. influenzae, Moraxella catarrhalis, Neisseria meningitides, Neisseria gonorrhoaeae, E. coli, Pseudomonas aeruginosa, and Enterobacteriaceae3.
Vancomycin and Zosyn do not cover atypical bacteria such as Legionella, Chlamydia, and Mycoplasma. Furthermore, vancomycin and Zosyn are not indicated for treatment of vancomycin-resistant Enterococcus (VRE), extended-spectrum beta-lactamases (ESBL) organisms, fungal infections, Stenotrophomonas maltophilia, viruses, tuberculosis, and parasites4.
Why should we be concerned about this antibiotic combination?
Mostly, there has been a contentious debate about this combination causing acute kidney injury (AKI). In a large retrospective cohort study, vancomycin and Zosyn were found to have more AKI, hypotension, and a significant increase in the length of hospitalization. The mechanism for the apparent increase in nephrotoxicity with this drug combination is not well understood and warrants further study in both animal models and humans5.
Side effects with any antibiotic are a cause for concern as well. In one study, 17.1 percent of hospitalized patents developed adverse drug effects that were associated with the administration of broad-spectrum antibiotics. Common manifestations were largely gastrointestinal but also had hepatobiliary, dermatologic, and renal involvement6.
Overuse of broad-spectrum antibiotics is especially problematic because of their potential for increased selection of resistant bacterial populations and their role in treating serious infections. Reducing broad-spectrum antibiotics can result in an estimated 26% reduction in inpatient C. difficle infections7.
Furthermore, a retrospective cohort study was conducted between 2012 and 2015 to determine the frequency and cause of inadequate initial antibiotic therapy with vancomycin and Zosyn in patients with severe sepsis and septic shock in the emergency department. Patients were reviewed to determine the appropriateness of antimicrobial therapy, risk factors for inappropriate use, and outcome data. The results showed vancomycin and Zosyn were inappropriate for 24% of patients with severe sepsis or septic shock, largely due to non-susceptible infections, particularly ESBL organisms and C. difficile. Patients with known chronic obstructive pulmonary disease (COPD), residence at a skilled nursing facility, history concerning for C. difficile, and immunosuppression would benefit from an alternative regimen8.
These findings demonstrate the need for judicious use of combination therapy and strengthen the need for antimicrobial de-escalation when appropriate to avoid deleterious effects1.
It is important we treat patients in a timely manner and with optimal doses of appropriate antibiotic therapy if there is a suspected diagnosis of sepsis or septic shock. However, it is imperative we take into account the patient’s past medical history such as a history of ESBL or other multi-drug resistant organisms, C-diff., multiple co-morbidities such as underlying kidney disease, immunosuppression, and drug intolerances or allergies in order to treat our patients effectively with minimal adverse reactions and to reduce the risk of antimicrobial resistance.