What is the difference between piperacillin combined with tazobactam and cefoperazone combined with sulbactam?📣📣📣

Due to the extensive use of antibiotics, bacterial resistance to antibiotics continues to rise. The most common pathogens of bacterial infectious diseases are caused by Gram-negative bacteria. The mechanism of resistance in Gram-negative bacteria is mainly the generation of different β-lactamases, such as penicillinase, cephalosporinase, carbapenemase and extended-spectrum β-lactamases (ESBLs). Most β-lactamases produced by bacteria are inactivated by binding to β-lactamase inhibitors. β-lactamase inhibitors can prevent the β-lactam ring in antibiotics from being hydrolyzed, thereby protecting the antibacterial effect of β-lactam antibiotics. In the combination of β-lactamase inhibitor and antibiotics, piperacillin combined with tazobactam and cefoperazone combined with sulbactam are drugs with high clinical use and good efficacy. However, what are the differences between them and how should choose them?

Comparison of antibacterial spectrum of piperacillin combined with tazobactam and cefoperazone combined with sulbactam.

	Piperacillin/tazobactam	Cefoperazone/sulbactamzxad
Acinetobacter	+	+++
Enterobacter	++	+++
Enterococcus	+	-
Escherichia coli	++++	++++
Haemophilus influenzae	+++	+++
Klebsiella	+++	++++
Methicillin-sensitive Staphylococcus aureus	+	+
Moraxella catarrhalis	+	+
Pseudomonas aeruginosa	++++	+++
Stenotrophomonas maltophilia	-	+++
Streptococcus	+	+
"-" means no effect. "+" means it works. The more "+" the table has, the stronger the effect.

Can they treat gram-positive infections?

In general, piperacillin combined with tazobactam and cefoperazone combined with sulbactam will not be used to treat pure gram-positive infections. Although cefoperazone combined with sulbactam may be effective against enterococci (eg, Streptococcus faecalis), cefoperazone combined with sulbactam is generally considered to be ineffective against enterococci. Ampicillin in combination with sulbactam and amoxicillin in combination with clavulanic acid are commonly used drugs for the treatment of gram-positive infections. They have a certain antibacterial ability against methicillin-sensitive staphylococcus aureus, enterococcus and streptococcus.

How effective are they in the treatment of bacterial infections that produce extended-spectrum β-lactamases?

In the in vitro drug susceptibility test, their sensitivity were over 80% to the ESBLs-producing strains. For patients with mild to moderate infection without secondary severe sepsis or septic shock, one of them can be selected according to the results of drug susceptibility testing. However, they are not the first choice for patients with severe infections. Carbapenems are the most effective and reliable drugs for the treatment of various infections caused by enterobacteriaceae that produce extended-spectrum β-lactamases. Studies have shown that the high-dose extended infusion regimen of piperacillin/tazobactam can achieve the best pharmacodynamics, but any regimen of cefoperazone/sulbactam can not achieve the desired pharmacodynamics . Therefore, piperacillin combined with tazobactam is more suitable for the empirical treatment of extended-spectrum β-lactamase-producing bacterial infections.

How effective are they in the treatment of stenotrophomonas maltophilia infections?

Patients with more severe infections generally require combination therapy. Usually, sulfamethoxazole-trimethoprim or tigecycline or quinolones are used as the basic drugs in combination with sensitive β-lactamase inhibitor complexes, usually cefoperazone/sulbactam is more commonly used.

How effective are they in the treatment of acinetobacter baumannii infections?

Piperacillin combined with tazobactam and cefoperazone combined with sulbactam both have potential antimicrobial activity. According to drug susceptibility testing, they can be used to treat acinetobacter baumannii infection. However, sulbactam has strong antibacterial activity against Acinetobacter spp. The combination of cefoperazone and it has synergistic antibacterial activity, and their susceptibility is higher than that of piperacillin/tazobactam. 

How effective are they in the treatment of pseudomonas aeruginosa infections?

Although they have antibacterial activity, some studies indicate that piperacillin/tazobactam is slightly more sensitive than cefoperazone/sulbactam. Although they have antibacterial activity, some studies indicate that piperacillin/tazobactam is slightly more sensitive than cefoperazone/sulbactam. Both of them can be used to treat patients with non-multidrug-resistant pseudomonas aeruginosa infections or with milder disease. Patients with multidrug-resistant pseudomonas aeruginosa infection or severe disease require combination with fluoroquinolone or aminoglycoside antibiotics.

How effective are they in the treatment of anaerobic bacteria infections?

Piperacillin/tazobactam is effective against most anaerobic infections. Cefoperazone/sulbactam is effective against infections such as Preobacterium melanogenum, Peptococcus, Peptococcus, Clostridium, Fusobacterium, Bacteroides, Eubacterium, and Lactobacillus.

What are their clinical applications?

Pneumonia:

• Community-acquired pneumonia: Patients who are hospitalized and have underlying diseases or are older than 65 years old, have high risk factors for Pseudomonas aeruginosa infection, or need to be admitted to the ICU can choose piperacillin/tazobactam or cefoperazone//sulbactam.
• Hospital-acquired pneumonia: They are not the first choice for patients with mild to moderate disease and no risk factors for drug resistance. As long as there are risk factors for multidrug resistance, patients with mild to moderate or severe disease need to be combined with other antibiotics.
• Structural lung disease: For patients with high risk factors for Pseudomonas aeruginosa infection, choose one of them. Depending on the patient's condition, monotherapy or in combination with other antibiotics may be used.
• Aspiration pneumonia: Neither of them would be the drug of choice for patients without high-risk factors for drug-resistant bacteria. Patients with community-acquired pneumonia and with inhalation factors should be treated according to the principles of hospital-acquired pneumonia and need to be covered with anaerobic bacteria.

Blood Infections:

For neutropenic, immunocompromised, and severe systemic infections, treatment should be empirical coverage of multidrug-resistant Gram-negative bacilli. β-lactamase inhibitor complexes are the preferred treatment option, and then the treatment can be adjusted based on the test results.

Abdominal infection:

Patients with mild or moderate infection: Combination of third-generation cephalosporins with metronidazole or β-lactamase inhibitor.

Severe infection in patients: β-lactamase inhibitor combination preparations or carbapenems are recommended as the drugs of choice.

Urinary tract infection:

Hospitalized and Severely Infected: When a patient has a pseudomonas aeruginosa infection, they can use either one and usually require a combination of other medications.

Complicated urinary tract infection: Hospitalization is required in patients with severe infection and/or suspected bacteremia. Piperacillin/tazobactam can be used for empirical antimicrobial therapy. Aminoglycosides can be combined if necessary, and treatment can then be adjusted based on bacterial susceptibility testing.

Fever with agranulocytosis:

High-risk patients should be treated with broad-spectrum antibiotics that cover Pseudomonas aeruginosa and other Gram-negative bacteria. Piperacillin combined with tazobactam and cefoperazone combined with sulbactam are both optional.