A few months ago, I visited a primary hospital and found that some patients with renal insufficiency were still using "conventional doses" of antibiotics, is this reasonable? Let's start with two cases:
Case 1
A 73-year-old male, admitted to the hospital for 3 days with fever, cough and chest tightness, with a history of coronary heart disease, hypertension, diabetes mellitus, and chronic renal insufficiency, was admitted to the hospital with a diagnosis of coronary heart disease, heart failure, atrial fibrillation, cardiac function grade III, pneumonia, and type I respiratory failure.
入院查血肌酐 137 μmmol/L。
予左氧氟沙星 0.5 iv gtt qd 抗感染治疗。
ECG during treatment showed QT interval prolongation and was not taken seriously.
On the 5th day of levoxitherapy, the patient developed torsion de pointes, which improved after rescue treatment such as lidocaine, and malignant arrhythmias such as torsades de pointes did not occur after the discontinuation of levoxigen.
Case 2
An 80-year-old woman admitted to hospital with cough, sputum production for 1 week. Admission diagnosis: pulmonary infection, coronary heart disease.
入院查血肌酐 203 μmmol/L。
Drowsiness and incontinence occurred 5 days after treatment with cefepime 2.0 IV GTT every 12 hours. Urgent CT of the head showed no obvious abnormalities. Mental improvement on day 2 after discontinuation of cefepime.
In the above two cases, adverse events occurred during hospitalization, mainly due to the failure to adjust the dose according to creatinine clearance in patients with renal insufficiency and elderly patients.
Renal function can reduce the excretion rate of antibiotics, and it is easy to accumulate in the body after the use of conventional or larger doses of antimicrobial drugs, resulting in high blood concentrations, which can easily induce adverse reactions of antibiotics.
Case 1: Elderly patient with renal insufficiency, 0.5 qd leads to accumulation of left oxygen, cardiac electrophysiologic toxicity of left oxygen is amplified, QT interval prolongation and torsade de pointes occur, and there is a tendency to develop ventricular fibrillation.
Case 2: In the same elderly patient with renal insufficiency, the regular dose of cefepime led to an abnormal increase in blood concentration, and a large amount of the drug passed through the blood-brain barrier, eventually leading to antibiotic encephalopathy.
01
What are the antibiotics that are mainly metabolized by the kidneys?
Most antibiotics are excreted in urine through the kidneys and in feces through bile to a lesser extent.
Antibiotics that are mainly metabolized by the kidneys are: most β-lactams (including penicillins, cephalosporins, carbapenes, etc.), aminoglycosides (such as amikacin, netimicin, etc.), quinolones (ciprofloxacin, levofloxacin, etc., except moxifloxacin), vancomycin, SMZ, acyclic guanosine, oseltamivir, nirmatrelvir/ritonavir, etc.
Therefore, for antibiotics metabolized by the kidneys, renal insufficiency or the elderly should consult the drug instructions before use, and adjust the dosage according to the creatinine clearance rate to prevent adverse reactions induced by drug accumulation.
02
Which antibiotics do not require dose adjustment in the case of renal insufficiency?
Antibiotics metabolized primarily by the liver generally do not require dose adjustment in renal insufficiency, and conventional doses such as:
Cefoperazone (currently most used in clinical practice is cefoperazone/sulbactam, and the dose still needs to be adjusted when renal insufficiency), ceftriaxone (it is not broken down in the body, but only inactive metabolites converted by the intestinal flora), moxifloxacin, macrolides (including azithromycin, etc.), clindamycin, metronidazole, linezolid, itraconazole, caspofungin, voriconazole (intravenous preparations contain the excipient sulfonbetacyclodextrin sodium, and the creatinine clearance rate is < 50 mL/min, which is easy to cause accumulation and nephrotoxicity, while oral preparations do not have this excipient), tigecycline, doxycycline, etc.
03
How is creatinine clearance (CrCl) calculated?
According to the Cockcroft-Gault formula [1]:
男性：肌酐清除率 =（140 - 年龄）× 体重/（0.818 × 肌酐（μmmol/L））
Female: × 0.85 based on the above results
04
Practice: How to consult the manual?
病例 1：患者的 CrCl =（140 - 73）× 50/0.818/137 = 29.9 mL/min。
Open the "Medication Assistant APP" on the mobile phone and find the instructions for levooxygen, it can be seen that when the CrCl is 20~49 mL/min, the first dose of 500 mg is recommended, and then 250 mg qd, which shows that the excessive dosage of this patient is the main cause of severe arrhythmia (as shown in the table below).
病例 2：患者的 CrCl =（140 - 80）× 50/0.818/203 × 0.85 = 15.3 mL/min。
Open the "Medication Assistant APP" and find the instructions of cefepime, it can be seen that when the CrCl is 11~29 mL/min, if the original plan is 2 g q12h, 1 g qd is recommended, and the excessive dosage of this patient is the main cause of antibiotic encephalopathy due to drug accumulation (as shown in the table below).
05
Other considerations?
The irrational use of antibiotics in clinical practice is not uncommon, in case 1 patients, it may be more reasonable to choose cephalosporins for anti-infection, quinolones have the risk of adverse reactions such as central nervous toxicity and cardiotoxicity, and the main advantage of quinolones over cephalosporins is that they can cover atypical pathogens, but Mycoplasma pneumoniae pneumonia is rare in elderly patients, and Legionella pneumonia is generally manifested as severe pneumonia, which is inconsistent with this case, and it is not necessary to choose quinolones similar, and it is recommended to avoid them as appropriate.
Reducing the irrational use of antibiotics also reduces the additional damage of antibiotics, and there is no harm if they are not used.
It is recommended that antibiotic dose selection in renal insufficiency should be consulted first and the dose adjusted according to creatinine clearance. However, there are also some special circumstances, such as linezolid is theoretically metabolized by the liver, and the instructions also believe that there is no need to adjust the dose when renal insufficiency, but some studies have found that linezolid is more common when the blood concentration is too high when renal insufficid, which can easily lead to adverse reactions of thrombocytopenia.
There is an expert consensus in China [2] that the recommended dose of linezolid for patients with renal insufficiency (non-hemodialysis) is 300 mg every 12 h (the conventional dose is 600 mg every 12 h), and it is recommended to monitor the blood concentration, and the recommended target trough concentration is 2~7 mg/L to achieve the best effectiveness and minimum blood toxicity.
Therefore, it is still recommended to check the dose of antibiotics for renal insufficiency, and learn the consensus of the latest guidelines to keep pace with the times.
06
summary
1. The indications of antibiotics should be strictly grasped in clinical treatment;
2. In addition to focusing on the antibacterial effect, antimicrobial treatment should also pay close attention to its adverse reactions, which may be life-threatening once they occur;
3. Patients with renal insufficiency and elderly patients should adjust the dose and medication interval according to the creatinine clearance;
4. If conditions permit, the blood concentration can be monitored, and the dose can be further adjusted according to the blood concentration;
5. Closely monitor the changes in the condition, identify adverse drug reactions as soon as possible, stop the drug immediately and give appropriate treatment.
This article is transferred from the Lilac Garden Medication Guide