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.

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What are the treatments for Pseudomonas aeruginosa?💊💊💊

Pseudomonas aeruginosa is a non-fermenting gram-negative bacillus and is a common opportunistic pathogen. It is widely distributed in the daily environment. Its main source is domestic sewage. It can cause lung infections, bloodstream infections, skin infections (often in people with burns), among others. In addition, Pseudomonas aeruginosa often causes nosocomial infections in patients. Studies have pointed out that patients with low immunity, skin and mucous membrane damage (such as mechanical ventilation, tracheal intubation, indwelling central venous catheter, etc.), structural lung disease (such as cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, etc.), as well as patients who are using broad-spectrum antibiotics and have been hospitalized for a long time have a higher risk of infection with Pseudomonas aeruginosa. In addition, in patients with cystic fibrosis, respiratory infections caused by Pseudomonas aeruginosa may develop into chronic infections that are more difficult to treat.

Commonly used drugs against Pseudomonas aeruginosa.

β-lactam antibiotics:

• Penicillin: Piperacillin 9 to 16g intravenously daily, divided into 3 to 4 times.
• Penicillin/β-lactamase inhibitor: Piperacillin/tazobactam 4.5g intravenously every 6 to 8 hours.
• Cephalosporins: Ceftazidime 2g intravenously every 8 hours. Cefoperazone 2g intravenously every 8 hours. Cefepime 2g intravenously every 8 to 12 hours.
• Third generation cephalosporins/β-lactamase inhibitor: Cefoperazone/sulbactam 3g intravenously every 8 hours.
• Monobactams: Aztreonam 2g intravenously every 6 to 8 hours.
• Carbapenems: Imipenem/cilastatin 0.5 g intravenously every 6 hours or 1 g intravenously every 6 to 8 hours. Meropenem is administered intravenously at 1 g every 6 to 8 hours.

Aminoglycosides:

• Gentamicin: The dose is 7mg/(kg x d).
• Tobramycin: The dose is 7mg/(kg x d).
• Amikacin: The dose is 15mg/(kg x d).

Quinolones:

• Ciprofloxacin: The dose is 0.4g every 8 to 12 hours.
• Levofloxacin: The dose is 0.5 to 0.75 g daily.

Other:

• Polymyxin B: The dose is 2.5 to 5 mg/(kg x d) by intravenous infusion, divided into 3 to 4 times.
• Polymyxin E: The dose is 2.5 to 5 mg/(kg x d) by intravenous infusion, divided into 3 to 4 times.
• Fosfomycin: The dose is 300mg/(kg x d) by intravenous infusion, divided into 2 to 3 times.

Among these anti-Pseudomonas aeruginosa drugs, aztreonam, aminoglycosides, polymyxin and fosfomycin generally need to be used in combination with other antibiotics, and are not used alone. Clinically, the course of treatment will be determined according to the patient's condition. If the patient's condition is stable within 3 days after taking the drug, the recommended treatment course is 8 days. If the patient's efficacy is poor after treatment, the course of treatment can be extended to 10 to 14 days.

The drug resistance mechanism of Pseudomonas aeruginosa and its recommended medication.

Pseudomonas aeruginosa develops drug resistance by expressing efflux pumps, forming biofilms, changing target sites and outer membrane proteins, and producing β-lactamases. Some studies have pointed out that the resistance rate of Pseudomonas aeruginosa to polymyxin and amikacin is low, but the resistance rate to carbapenem can be as high as 23%. Drug-resistant Pseudomonas aeruginosa can be divided into:

• Multi-drug resistance: Pseudomonas aeruginosa is not susceptible to 3 or more antibacterial drugs against Pseudomonas aeruginosa.
• Extensive drug resistance: generally refers to that Pseudomonas aeruginosa is not sensitive to other antibiotics and only sensitive to polymyxins.
• Pandrug resistant: Pseudomonas aeruginosa is not sensitive to existing antibiotics.

Dual therapy regimens for extensively drug-resistant Pseudomonas aeruginosa:

1. Combined use of two β-lactam antibiotics: Ceftazidime + Piperacillin/tazobactam, Aztreonam + Piperacillin/tazobactam, Ceftazidime + Aztreonam, Ceftazidime + Cefoperazone/sulbactam.
2. Ciprofloxacin-based: Combine a β-lactam antibiotic or aminoglycoside.
3. Polymyxin-based: Combine a β-lactam antibiotic, ciprofloxacin, fosfomycin or rifampicin.
4. Based on β-lactam antibiotics: combined with ciprofloxacin, aminoglycoside or fosfomycin.

Triple therapy for extensively drug-resistant Pseudomonas aeruginosa:

1. Polymyxin + β-lactams + Ciprofloxacin.
2. Polymyxin + β-lactams + Fosfomycin.
3. Polymyxin (intravenous) + Polymyxin (aerosol inhalation) + Carbapenems.
4. Aztreonam + Ceftazidime + Amikacin.

Due to the increased risk of side effects (eg, increased nephrotoxicity with polymyxin and aminoglycosides, immune-mediated thrombocytopenia with rifampicin and piperacillin), rational drug selection and monitoring The patient's drug response.

Inhaled antimicrobials are believed to be the mainstay of treatment for Pseudomonas aeruginosa-related lung infections.

The goal of treatment for pulmonary infections caused by Pseudomonas aeruginosa is to reduce bacterial counts in the respiratory tract and improve patient outcomes. Antibiotics for inhalation have the advantage of a dosage form that allows the drug to accumulate in the respiratory tract to increase local drug concentration. This is believed to significantly improve the patient's respiratory symptoms and improve the patient's quality of life. There are now many inhaled formulations of antibiotic drugs into the field of research.

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Important points about the use of azithromycin.📜📜📜

Azithromycin is a macrolide antibiotic. The structure of these antibiotics has a giant ring lactone and has one or more deoxysugar linkages. They can be used as replacement drugs in patients allergic to β-lactam antibiotics. Azithromycin has many clinical advantages. There is no need for a skin test before using it. It has a broad antibacterial spectrum. Under normal circumstances, patients only need to take it once a day, which can improve patient compliance. Therefore, it is a very commonly used oral antibiotic. The following will explain how to properly use azithromycin.

Pharmacological effects.

Azithromycin irreversibly binds to the 23SrRNA of the 50S ribosomal subunit of susceptible bacteria, thereby inhibiting the transfer step of bacterial protein synthesis and preventing the assembly of the 50S ribosomal subunit. 

Dosage form and usage.

Azithromycin is clinically available in different dosage forms, but their potency is not necessarily the same. They need to pass the consistency evaluation to be considered equal.

• Tablets ≠ dispersible tablets ≠ enteric-coated tablets. Capsule ≠ soft capsule ≠ enteric-coated capsule.

Different dosage forms are used differently. 

For azithromycin tablets, take orally once daily and swallow the tablet whole. It can be taken with or without food.

For azithromycin capsules, take orally once daily and swallow the tablet whole. It should be taken at least one hour before meal or at least two hours after meal. 

Azithromycin dispersible tablets, enteric-coated tablets or soft capsules are generally taken at least one hour before meal or at least two hours after meal. The actual situation is based on the drug instruction.

The half-life of azithromycin is 68 hours, which is relatively long. Patients stop taking it after 3 days and it will still work in the body for 3 to 4 days. Therefore, mild and moderate infection patients take 500mg once a day for three days, with a total dose of 1500mg. 

Is azithromycin preferred for mycoplasma pneumonia?

In the past, azithromycin was the first choice for mycoplasma pneumonia. However, with the increasing rates of resistance to erythromycin and azithromycin in mycoplasma isolated from adult patients with community-acquired pneumonia. Although these mycoplasmas have increased resistance to macrolides, they remain susceptible to quinolones, doxycycline, or minocycline. When a patient is suspected of having mycoplasma pneumonia, antibiotics are selected according to his age: 

• When the patient is less than 8 years old, azithromycin is the first choice for him.
• When the patient is 8 years or older, azithromycin is preferred for him. Alternatively, doxycycline or minocycline may be used on him.
• When the patient is 18 years or older, doxycycline and minocycline are preferred. In addition, quinolone antibiotics such as moxifloxacin can also be considered for him.

Off-label medication.

In addition to its broad antibacterial effects, azithromycin has many other effects including disruption of biofilms, changes in macrophage phenotype, modulation of the immune system, and regulation of airway surface liquid electrolytes and mucus. Therefore, azithromycin will be used off-label.

1. Prevention and treatment of bronchial asthma: Asthma patients have persistent symptoms despite the use of combined treatment with moderate or high doses of inhaled corticosteroids and long-acting β₂ agonists. Addition of azithromycin can reduce acute asthma attack and improve quality of life in patients. Patients received oral azithromycin 250 to 500 mg three times a week for 26 to 48 weeks.
2. Treatment of adult bronchiectasis: For patients with acute exacerbations of bronchiectasis greater than or equal to 3 times per year, it is recommended that patients receive oral low-dose azithromycin for at least 3 months. The initial therapeutic dose is 250 mg orally, 3 times a week to once a day. Adjust the dose or discontinue the drug according to clinical efficacy and adverse reactions.
3. Treatment of chronic obstructive pulmonary disease: Consider adding azithromycin to patients who still experience acute exacerbations on combination therapy with inhaled corticosteroids, long-acting β₂ agonists and long-acting muscarinic antagonists, especially those with a history of smoking. Studies have shown that cigarette-induced lung inflammation and emphysema in mice can be alleviated by low-dose azithromycin.

Precautions for medication.

The capsule form of azithromycin should not be taken with food.

Azithromycin promotes gastrointestinal motility and may cause dysbiosis in the gastrointestinal tract. Therefore, patients who develop bloody or watery stools during medication or for 2 months or longer after medication should go to see a doctor as soon as possible.

Azithromycin prolongs the QT interval. Patients should go to see a doctor as soon as possible if they experience cardiac discomfort during or after taking azithromycin.

Azithromycin is hepatotoxic and ototoxic. If the patient develops related symptoms, the drug should be discontinued immediately.

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Treatment options for Helicobacter pylori.👀

Helicobacter pylori (Hp) is a bacterium with a high infection rate in clinical practice. It can cause stomach ulcers and chronic gastritis and other stomach diseases. The long-term effects of these stomach problems can even lead to stomach cancer. Some studies have pointed out that the incidence of stomach disease caused by Hp is about 6 times that of stomach disease caused by other reasons. About 90% of patients with chronic gastritis and gastric ulcers carry Helicobacter pylori.

Indications for Helicobacter pylori.

The infection rate of Helicobacter pylori in the world is very high. Hp infection rates in some countries exceed 50%. Gastritis caused by Hp is an infectious disease. Treatment is generally necessary for Hp-positive patients. For Hp-positive patients with the following indications, they should undergo Hp eradication therapy. 

Eradication therapy is strongly recommended for Hp-positive patients with the following indications:

1. Peptic ulcer with or without activity and with or without a history of complications.
2. Gastric mucosa-associated lymphoid tissue.

Eradication therapy is recommended for Hp-positive patients with the following indications:

1. Has a family history of gastric cancer.
2. Chronic gastritis is accompanied by symptoms of gastric mucosal atrophy, erosion or indigestion.
3. Long-term use of proton pump inhibitors (PPIs).
4. The treatment plan requires long-term use of non-steroidal anti-inflammatory drugs.
5. Early gastric tumors have undergone endoscopic resection or subtotal gastrectomy.
6. Idiopathic thrombocytopenic purpura.
7. Unexplained iron deficiency anemia.
8. Other Hp-related diseases such as hyperplastic gastric polyps, lymphocytic gastritis.
9. Hp infection has been confirmed.

Drugs that can eradicate Helicobacter pylori.

The main treatment regimen for empirical eradication of Helicobacter pylori is PPI + 2 kinds of antibacterial drugs + bismuth. It is recommended to use for 10 or 14 days. Eradication rates with these regimens can reach 85 to 94%.

1. Proton pump inhibitors.

PPIs can inhibit the secretion of gastric acid and increase the pH of the stomach. It will increase the chemical stability of antibiotics, the concentration of antibiotics in the stomach and reduce the minimum inhibitory concentration to enhance the effect of antibiotics. In order to improve the eradication rate, it should generally be used the drugs with high curative effect, stable action and less influence by CYP2C19 gene polymorphisms, such as rabeprazole. They are generally recommended to be taken twice a day, half an hour before meals. 

1. Omeprazole: It is a first-generation PPI. Its recommended dose is 20mg daily. Its onset is slower.
2. Lansoprazole: It is a first-generation PPI. Its recommended dose is 30mg daily. It onset is faster than omeprazole.
3. Pantoprazole: It is a first-generation PPI. Its recommended dose is 40mg daily. It onset is similar to that of omeprazole.
4. Rabeprazole: It is a second-generation PPI. Its recommended dose is 10mg or 20mg daily. It onset is the fastest.
5. Esomeprazole: It is a second-generation PPI. Its recommended dose is 20mg daily. It onset is similar to that of lansoprazole.

2. Antibacterial drugs.

Acidic environments reduce their efficacy. It is generally recommended to take it after meals. The following are commonly used antibacterial drug combinations:

• Amoxicillin 2 times a day, 1000mg each time + Clarithromycin 2 times a day, 500mg each time.
• Amoxicillin 2 times a day, 1000mg each time + Levofloxacin 500mg once a day or 200mg twice a day.
• Amoxicillin 2 times a day, 1000mg each time + Furazolidone 2 times a day, 100 mg each time.
• Tetracycline 3 or 4 times a day, 500mg each time + Metronidazole 3 or 4 times a day, 400 mg each time.
• Tetracycline 3 or 4 times a day, 500mg each time + Furazolidone 2 times a day, 100 mg each time.
• Amoxicillin 2 times a day, 1000mg each time + Metronidazole 3 or 4 times a day, 400 mg each time.
• Amoxicillin 2 times a day, 1000mg each time + Tetracycline 3 or 4 times a day, 500mg each time.

Gastric acid had relatively little effect on the activity of tetracycline, metronidazole, and furazolidone. The other effects of gastric acid were amoxicillin > clarithromycin > levofloxacin.

3. Bismuth.

Bismuth pectin (undetermined standard dose) and bismuth citrate (220 mg) are recommended to be taken twice a day, half to one hour before meals. Stools will turn black after taking bismuth. Short-term use of bismuth for 1 to 2 weeks has a high safety. Helicobacter pylori is not resistant to bismuth because it is directly killed by bismuth. Bismuth can additionally increase the eradication rate of resistant strains of Hp by 30 to 40%. A quadruple regimen containing bismuth should be used whenever possible in the empirical treatment of Hp, unless the patient has a contraindication to bismuth or resides in a low resistance rate.

How to choose a treatment plan?

The choice of treatment regimen is to choose a combination of antibiotics. The choice of PPI and bismuth is generally not limited unless the patient has a contraindication or intolerance. The selection of antibiotics should be based on the patient's allergy history, medication history, and local Hp antibiotic resistance. Efficacy, cost, convenience, and adverse reactions should also be considered.

1. Initial empirical treatment.

The above combinations of antibacterial drugs are not divided into first-line or second-line. The combination with high efficacy should be used in the initial treatment. However, Combinations containing levofloxacin are not intended as initial treatment regimens. The main reason for the decrease in eradication rate is the increased drug resistance of Hp. If Hp is resistant to one of the two antibacterial drugs, the eradication rate drops to 50 to 60%. If Hp is resistant to both antibiotics, the eradication rate is only about 10%. Antibiotics were selected according to the resistance of local Hp. Drug susceptibility testing can be performed if necessary. Amoxicillin generally has a strong effect on Hp and is not easy to develop drug resistance. Patients without allergies have fewer adverse reactions. It can be considered as the first choice. Furazolidone has more serious adverse reactions. It is only used for Hp infections that are difficult to eradicate.

Primary resistance rate of Hp:

	Resistance rate
Amoxicillin	0-5%
Clarithromycin	20-50%
Furazolidone	0-1%
Levofloxacin	20-50%
Metronidazole	40-70%
Tetracycline	0-5%

Eradication rates and incidence of adverse effects of treatment regimens:

	Eradication rate	The incidence of adverse reactions
Amoxicillin + Clarithromycin	85-94%	Low
Amoxicillin + Levofloxacin	85-89%	Medium
Amoxicillin + Tetracycline	85-89%	Medium
Tetracycline + Metronidazole	85-94%	Medium to high
Tetracycline + Furazolidone	85-94%	Medium to high
Amoxicillin + Metronidazole	85-94%	Medium to high
Amoxicillin + Furazolidone	85-94%	Medium to high

2. After failure of initial treatment.

Choose one of the remaining treatment options for treatment. The selection should refer to past treatment regimens. It is generally not reused. 

Metronidazole at conventional doses is fully functional when Hp is not resistant, but it is completely ineffective when resistant. Its dose can increase to 1600mg daily in 4 divided doses to overcome drug resistance. Therefore, if repeated use of metronidazole is required, its dose needs to be increased to 1600 mg per day. When this dose has been used for the initial treatment, it should not be used again. 

In addition, increasing the dose of metronidazole (1600mg/day) or furazolidone (300mg/day) can improve the efficacy, but the adverse reactions will also increase.

3. Treatment of patients with penicillin allergy.

Tetracycline can be used instead of amoxicillin. It is recommended to use tetracycline in combination with furazolidone or metronidazole. Tetracycline combined with levofloxacin is also effective.

When tetracycline cannot be used, clarithromycin can be used instead. Such as clarithromycin combined with furazolidone, metronidazole or levofloxacin.

Prevention of Hp.

The main route of Hp infection is the digestive tract. Saliva can be its carrier. Therefore, pay attention to the hygiene of tableware and disinfect regularly.

Studies have shown that Hp can survive in fresh water for at least 3 years. It also survives 4 to 10 days in tap water. Water should be cooked thoroughly before drinking.

The development of an Hp vaccine may be the best way to prevent infection in the future.

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The difference between imipenem, meropenem and biapenem.👀

Carbapenems are a class of atypical β-lactam antibiotics with the broadest
antibacterial spectrum. They have strong antibacterial activity against Gram-positive, Gram-negative, and anaerobic bacteria. At present, imipenem, meropenem and biapenem are commonly used in clinical practice. Carbapenems bind to a variety of bacterial penicillin binding proteins (PBPs). This will prevent the synthesis of the cell wall and play a role, which has a relatively significant post antibiotic effect (PAE).

Characteristics of imipenem, meropenem and biapenem.

Imipenem: It is the first carbapenem approved for clinical use. It is metabolically inactivated by dehydrogenase I (DHP-I) in human kidney epithelial cells. Therefore, a specific enzyme inhibitor, cilastatin, was added to block the metabolism of imipenem in the kidneys, thereby ensuring sufficient antibacterial concentration of imipenem in urine. At the same time, cilastatin can also prevent imipenem from entering renal tubular epithelial cells to reduce its excretion and reduce renal toxicity. Imipenem and Cilastatin are β-lactamase stable. It has a broad antibacterial spectrum. It has strong activity against most Gram-positive and Gram-negative bacteria.

Meropenem: It is more stable to DHP-I and more active against Gram-negative bacteria than imipenem, especially Pseudomonas aeruginosa. Meropenem easily penetrates the blood-brain barrier and can effectively treat intracranial infections. At the same time, it has no affinity for γ-aminobutyric acid receptors. Its safety in the central nervous system is better than that of imipenem. It is more suitable for the treatment of the elderly, children and patients with central nervous system infection or severe infection accompanied by mental symptoms.

Biapenem: Compared with other carbapenems, it has lower nephrotoxicity and central nervous system toxicity.

• Anti-Gram-positive bacteria activity: Imipenem > Biapenem, Meropenem.
• Anti-Gram-negative bacteria activity: Meropenem > Biapenem > Imipenem.
• Anti-Pseudomonas aeruginosa activity: Meropenem = Biapenem > Imipenem.
• Anti-anaerobic activity: Biapenem > Imipenem = Meropenem.

Carbapenems are generally resistant to Stenotrophomonas maltophilia (chromosome-mediated β-lactamase that candhydrolyze carbapenems), Burkholderia cepacia, Enterococcus faecium, oxacillin-resistant Staphylococcus aureus and so on are ineffective.

Dosage of imipenem, meropenem and biapenem.

Imipenem/Cilastatin: 1-2 g in 3-4 divided doses daily is recommended for most infections. The maximum dose is 4g per day. It does not require a skin test. Patients with renal insufficiency require dose adjustment.

Meropenem: The recommended dose is 0.5 or 1 g every 8 hours. Meningitis patients 2g every 8 hours. The maximum dose is 6g per day. It does not require a skin test. Patients with renal insufficiency require dose adjustment.

Biapenem: The recommended dose is 0.3 g every 12 hours. The maximum dose is 1.2g per day. It does not require a skin test. Patients with renal insufficiency require dose adjustment.

Precautions of imipenem, meropenem and biapenem.

Imipenem/Cilastatin: When the dose is ≤ 0.5g, the intravenous infusion time should be no less than 20-30 minutes. When the dose is > 0.5g, the intravenous infusion time should not be less than 40-60 minutes. It has partial cross-allergic reactions with other β-lactams, penicillin, and cephalosporins. When it is combined with sodium valproate, it causes the sodium valproate concentration to decrease. This will increase the risk of seizures. Furthermore, increasing the dose of sodium valproate was not sufficient to overcome the interaction between them. Imipenem/Cilastatin can cause central nervous system accumulation and lead to psychiatric symptoms. It may also cause pseudomembranous colitis. If using imipenem/cilastatin while breastfeeding, breastfeeding should be discontinued.

Meropenem: Intravenous push time should be greater than 5 minutes. It has partial cross-allergic reactions with other β-lactams, penicillin, and cephalosporins. When it is combined with sodium valproate, it causes the sodium valproate concentration to decrease. This will increase the risk of seizures. It also competes with probenecid to activate tubular secretion and inhibit renal metabolism. This results in prolonged half-life of meropenem and increased plasma concentrations. Patients with a history of epilepsy or central nervous system dysfunction are more likely to develop central nervous system symptoms. It may also cause symptoms of vitamin K deficiency. If using meropenem while breastfeeding, breastfeeding should be discontinued.

Biapenem: The intravenous infusion time should be 30-60 minutes each time. It has partial cross-allergic reactions with other β-lactams, penicillin, and cephalosporins. When it is combined with sodium valproate, it causes the sodium valproate concentration to decrease. It can cause epileptic seizures. Patients with a history of epilepsy or central nervous system dysfunction are more likely to develop central nervous system symptoms. It may also cause symptoms of vitamin K deficiency. Safety during breastfeeding has not been established.

Clinical application characteristics of imipenem, meropenem and biapenem.

Imipenem/Cilastatin: When it comes into contact with bacteria, it turns the bacteria into a spherical shape. The endotoxin released by bacteria is reduced and the initial bactericidal effect is extremely strong. It is widely distributed in the body. It can cross the placental barrier, but it cannot cross the blood-brain barrier. It can cause central nervous system toxicity, so it should not be used in the treatment of meningitis. Its sterilization speed is fast. 1 hour bactericidal activity is twice that of meropenem. It is ineffective against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. The activity against gram-positive bacteria is stronger than that of meropenem.

Meropenem: When it comes into contact with bacteria, it swells the bacteria. Bacteria release a lot of endotoxin, and the initial bactericidal effect is poor. It can cross the blood-brain barrier. It can reach effective concentrations in cerebrospinal fluid. Common adverse reactions are similar to imipenem, but it may have a slightly lower risk of seizures than imipenem. Meropenem is the first choice for patients with renal insufficiency and central nervous system disease. The activity against Acinetobacter baumannii is lower than that of imipenem. However, the ability to resist Gram-negative bacteria is 2-16 times that of subpulmonary penem and the anti-Pseudomonas aeruginosa effect is 2-4 times that of imipenem.

Biapenem: When it comes into contact with bacteria, it turns the bacteria into a spherical shape. The endotoxin released by bacteria is reduced and the initial bactericidal effect is extremely strong. Multiple doses do not accumulate in the body. It is ineffective against Enterococcus faecium and methicillin-resistant Staphylococcus aureus. Its antibacterial activity is similar to meropenem. The activity of inhibiting Pseudomonas aeruginosa and anaerobic bacteria is 2-4 times that of imipenem. It has extremely low nephrotoxicity and CNS toxicity compared to other carbapenems. It does not induce epilepsy. It can be used in the treatment of bacterial meningitis. Adverse reactions are also relatively few.

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Knowledge about streptococcal infection.📜📜📜

Streptococcus has a wide variety of bacteria and is widely distributed. Some streptococci are normal human flora, while others are pathogenic bacteria of humans. 

1. What is streptococcus?

Streptococcus is a gram-positive cocci and the bacteria are purple after Gram staining. According to whether hemolysis occurs on blood agar, Streptococcus bacteria are divided into three categories: α-hemolytic streptococcus, β-hemolytic streptococcus and γ-streptococcus.

Medically important streptococci:

1. α-hemolytic streptococcus: Streptococcus pneumoniae, Streptococcus viridans.
2. β-hemolytic streptococcus: Group A Streptococcus (also call streptococcus pyogenes), group B, group C, group D and group G streptococcus.
3. γ-streptococcus: They are generally not causing disease.

2. Common streptococcus infections:

• Streptococcus pneumoniae: Streptococcus pneumoniae is distributed in the nasopharynx of 5-10% of adults and 20-40% of children. Most of the strains are not pathogenic and only a few strains are pathogenic. It is the main pathogen of bacterial pneumonia. It causes diseases such as acute bacterial otitis media, acute bacterial sinusitis, community-acquired pneumonia and lung abscess.
• Streptococcus viridans: It is mainly distributed in the oropharynx and gastrointestinal tract. It1 is a common pathogen causing dental caries, infective endocarditis and bacteremia.
• Streptococcus pyogenes: It is mainly distributed in the throat and is the most pathogenic bacteria among streptococci. It accounts for about 90% of streptococcal infections. It is the main pathogen of acute bacterial pharyngitis and tonsillitis. It can also cause lymphangitis, acute cellulitis, acute rheumatic fever, and glomerulonephritis.

3. Commonly used antibacterial drugs for streptococcal infections.

• Penicillin is the first choice for streptococcal infections. The antibacterial activity of the first and second generation cephalosporins against Streptococcus pneumoniae is less than penicillin. The drug resistance of streptococcus is caused by genetic mutations. Streptococcus pneumoniae is also less resistant to them. Streptococcus is not sensitive to penicillin. Amoxicillin, ceftriaxone and cefotaxime will have good antibacterial activity. 
• Penicillin-resistant Streptococcus pneumoniae is highly sensitive to vancomycin, linezolid and carbapenems.
• The resistance rate of macrolides and clindamycin is high.
• Aminoglycosides have no antibacterial activity against streptococci, but have synergistic effects with β-lactam antibiotics.

Acute bacterial pharyngitis and tonsillitis:

The common pathogen is group A hemolytic streptococcus. Penicillin is the first choice. Optional amoxicillin. Amoxicillin/clavulanic acid should not be used. This is mainly because hemolytic streptococcus does not produce β-lactamase, and clavulanic acid is useless at all. Since non-suppurative complications (acute rheumatic fever and glomerulonephritis) can occur after infection of group A hemolytic streptococcus, antibacterial treatment is aimed at removing bacteria and the course of treatment takes 10 days.

Acute bacterial otitis media and acute bacterial sinusitis:

The common pathogens are Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae. The first choice is amoxicillin or amoxicillin/clavulanic acid. 

Mainly reasons:

• Anti-Gram-positive bacteria activity (group A hemolytic streptococcus, streptococcus pneumoniae): amoxicillin ≈ penicillin.
• Anti-Gram-negative bacteria activity (Moraxella catarrhalis, Haemophilus influenzae): amoxicillin/clavulanic acid> amoxicillin> penicillin.

	Common pathogens	Antibacterial drugs
Acute bacterial pharyngitis and tonsillitis	Group A hemolytic streptococcus	l   Penicillin, amoxicillin. l   Patients who are allergic to penicillin can choose tetracyclines or fluoroquinolones that are sensitive to hemolytic streptococci (such as levofloxacin, moxifloxacin).
Acute cellulitis and lymphangitis.	Group A hemolytic streptococcus	l   Penicillin, amoxicillin. l   Amoxicillin/clavulanic acid, ceftriaxone.
Acute bacterial otitis media.	Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae.	l   Amoxicillin. l   If Moraxella catarrhalis and Haemophilus influenzae which producing β-lactamase strains are common in the local area, amoxicillin/clavulanic acid should be used. l   If the patient has no effect after taking the medicine for 3 days, it should be considered as possible penicillin-resistant Streptococcus pneumoniae infection. Ceftriaxone should be used.
Acute bacterial sinusitis.	Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae.	l   Amoxicillin/clavulanic acid.
Infective endocarditis	Streptococcus viridans.	l   Penicillin is used in combination with gentamicin. l   Combine ceftriaxone or cefotaxime with gentamicin.
Purulent meningitis (age < 1 month)	Group B hemolytic streptococcus, Escherichia coli, Listeria and Klebsiella pneumoniae.	l   Combine ceftriaxone or cefotaxime with ampicillin. l   Gentamicin is combined with ampicillin.

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