What organisms are not covered by Zosyn (Piperacillin/Tazobactam)?

From the Guidelines

Zosyn (piperacillin-tazobactam) does not cover methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecium, many Enterococcus faecalis strains, atypical organisms like Mycoplasma and Chlamydia, and most fungi and viruses. It also has limited activity against many multi-drug resistant gram-negative organisms such as carbapenem-resistant Enterobacteriaceae (CRE) and some strains of Pseudomonas aeruginosa with specific resistance mechanisms 1. Additionally, Zosyn is not effective against Mycobacterium tuberculosis or other mycobacterial species. This coverage gap exists because Zosyn is primarily a beta-lactam/beta-lactamase inhibitor combination that works by disrupting bacterial cell wall synthesis, which is ineffective against organisms with alternative resistance mechanisms like altered penicillin-binding proteins (as in MRSA) or those lacking a traditional cell wall structure (like mycoplasma) 1. When treating infections potentially caused by these uncovered pathogens, additional or alternative antimicrobial agents should be considered based on local susceptibility patterns and patient-specific factors. Some key points to consider when using Zosyn include:

• Its use in patients with ESBLs infections is still controversial, even if in stable patients, it may be still a therapeutic chance 1
• The use of piperacillin/tazobactam in patients with ESBLs infections should be guided by local resistance patterns and patient-specific factors 1
• Zosyn has broad-spectrum activity, including anti-Pseudomonas effect and anaerobic coverage, making it an interesting option for management of severe intra-abdominal infections 1
• However, its use should be limited to preserve activity of this class of antibiotics due to the concern of emerging carbapenem-resistance 1

From the FDA Drug Label

Piperacillin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section The following in vitro data are available, but their clinical significance is unknown At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for piperacillin. However, the safety and effectiveness of piperacillin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Zosyn (piperacillin and tazobactam) does not cover:

• MRSA (Methicillin-resistant Staphylococcus aureus): The label does not mention coverage for MRSA.
• Vancomycin-resistant Enterococci (VRE): The label does not mention coverage for VRE.
• β-lactamase-producing Haemophilus influenzae: The label mentions that non-β-lactamase-producing strains are susceptible, but does not provide information on β-lactamase-producing strains.
• Certain strains of Neisseria gonorrhoeae: The label mentions that β-lactamase testing is recommended to detect one form of penicillin resistance in Neisseria gonorrhoeae, but does not provide information on the coverage of piperacillin for these strains.
• Streptococcus pneumoniae and Streptococcus pyogenes with reduced susceptibility to penicillin: The label mentions that dilution (MICs) susceptibility test methods and interpretative criteria for assessing the susceptibility of these microorganisms to piperacillin have not been established. 2

From the Research

Zosyn Coverage

Zosyn, also known as piperacillin-tazobactam, is a broad-spectrum antibiotic used to treat various bacterial infections. However, there are certain bacteria that Zosyn may not effectively cover.

• Pseudomonas aeruginosa resistance: According to 3, Pseudomonas aeruginosa is a challenging pathogen to treat due to its limited antibiotic options and emerging resistance. While Zosyn has activity against Pseudomonas aeruginosa, resistance rates are increasing, making it essential to consider other treatment options.
• Vancomycin-resistant Enterococcus (VRE): As mentioned in 4, VRE is a significant concern, and Zosyn may not be effective against these strains. However, the study found that a combination of meropenem, piperacillin, and tazobactam showed activity against VRE.
• Methicillin-resistant Staphylococcus aureus (MRSA): Zosyn is not typically considered a first-line treatment for MRSA infections. As stated in 5, vancomycin and daptomycin are preferred options for initial treatment, while ceftaroline and combination therapies may be used for persistent or resistant MRSA bacteremia.
• Specific bacterial strains: The effectiveness of Zosyn can vary depending on the specific bacterial strain. For example, 4 found that USA100-SCCmec type II MRSA isolates were less susceptible to Zosyn, while USA300-SCCmec type IV isolates were more susceptible.

It is essential to note that antibiotic resistance patterns can vary by region and institution, and local epidemiology should guide treatment decisions. Additionally, combination therapies, such as vancomycin plus ceftaroline, may be effective for persistent or resistant infections, as shown in 6.