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.

Read More

What is diabetic ketoacidosis❓❓❓

One of the most common acute complications of diabetes is diabetic
ketoacidosis. The fatality rate of diabetic ketoacidosis in elderly patients with diabetes is as high as 5 to 16%. Therefore, we should master the diagnosis and treatment of diabetic ketoacidosis.

What are ketone bodies?

Fats are broken down into glycerol and fatty acids. Fatty acids are oxidatively broken down in the liver to form acetone, β-hydroxybutyric acid and acetoacetic acid. These three intermediate products are collectively referred to as ketone bodies. Since both acetoacetic acid and beta-hydroxybutyric acid are acidic substances, they can cause acidosis when they accumulate in large amounts in the body. In the blood, acetone accounts for only about 2% of the total ketone bodies, acetoacetic acid accounts for 28% and β-hydroxybutyric acid accounts for 70%. The blood concentration of β-hydroxybutyrate can directly reflect the ketone bodies in the body. However, the urine ketone measurement method can only measure acetone and acetoacetic acid, but not β-hydroxybutyric acid. 

What are the main causes of diabetic ketoacidosis?

Infection is the most common cause of diabetic ketoacidosis. Inappropriate dose reduction or interruption of insulin therapy is also a common cause of it. Insulin promotes the synthesis of fatty acids and glycerol into fat. When a patient's insulin is acutely deficient, it accelerates the breakdown of fat and increases the concentration of free fatty acids. Increased free fatty acid concentrations are oxidatively broken down in the liver to generate large amounts of ketone bodies. It will cause ketoacidosis.

How can a patient be diagnosed with diabetic ketoacidosis?

A lack of insulin in diabetics can increase blood sugar and accelerate fat breakdown. Hyperglycemia can cause osmotic diuresis. It causes dehydration and electrolyte loss in patients. Accelerated lipolysis increases free fatty acids in the patient's body. The oxidation and decomposition of fatty acids into ketone bodies will also increase. It can cause acidosis in patients.

Laboratory tests:

Blood sugar > 13.9 mmol/L.

Blood ketone ≥ 3 mmol/L or urine ketone(++).

Blood pH < 7.3 and/or HCO₃- < 18 mmol/L.

Diabetic ketoacidosis can be diagnosed with the above test results. The normal blood ketone value is 0.03 to 0.5 mmol/L. Plasma pH is normal 7.35 to 7.45. Serum HCO₃^- normal value is 22 to 27mmol/L. The clinical manifestations of diabetic ketoacidosis are lethargy, headache, abdominal pain, nausea, vomiting and rapid breathing (the exhaled breath will smell like rotten apples with acetone). Severe cases can cause dehydration, varying degrees of disturbance of consciousness and even coma.

What is the treatment for diabetic ketoacidosis?

Rehydration therapy: It is the primary treatment for patients with diabetic ketoacidosis. 0.9% Sodium Chloride Injection is the recommended treatment of choice. In principle, the rehydration treatment should be fast first and then slow. 1.0 to 1.5 L of normal saline should be infused during the first hour, and pre-estimated fluid losses should be replenished within the first 24 hours.

Insulin therapy: Insulin doesn't just lower a patient's blood sugar. It also reduces fat breakdown and inhibits the production of ketone bodies. Insulin is recommended as a continuous intravenous infusion of 0.1 U/kg/h. Insulin will generally correct ketosis more slowly than hyperglycemia. Therefore, when the patient's blood glucose was lowered to 11.1 mmol/L, the insulin input needed to be reduced and the patient started to be given 5% dextrose. It can maintain the patient's blood sugar at 8.3 to 11.1 mmol/L until the diabetic ketoacidosis is relieved.

Potassium supplementation therapy: If the patient's serum potassium is less than 3.3mmol/L, potassium supplementation therapy should be given priority to the patient. Insulin therapy should be started when the patient's serum potassium rises to 3.3 mmol/L. Cell membrane Na+-K⁺-ATPase is activated by insulin. It increases the intracellular potassium concentration, thereby reducing the blood potassium concentration. If the patient has normal urine output but serum potassium is less than 5.2 mmol/L after starting rehydration therapy and insulin, the patient should receive intravenous potassium supplementation. In general, 1.5 to 3.0 g of potassium chloride is added to each liter of infusion solution to maintain the patient's serum potassium level between 4 and 5 mmol/L.

Correction of acidosis: lipolysis is inhibited by insulin. It reduces the production of ketone bodies so that the acidosis is corrected. If the patient's circulation is not depleted, they generally do not need additional alkaline supplements. Generally, the use of 5% sodium bicarbonate solution for alkaline supplementation is only considered in the case of patients whose pH is less than or equal to 6.9.

Read More