Super full summary! The distribution of various types of antibacterial drugs throughout the body, 7 tables are sorted out

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Commonly used antibacterial drugs, how are they distributed in various tissues in the body?

The concentration of antibacterial drugs at the site of infection directly determines the efficacy of antibacterial drugs and the duration of antibacterial activity. The penetration of the drug to the tissue depends on the fat solubility of the drug, the relative molecular mass, the molecular structure and the binding rate of serum proteins.

Hydrophilic antibacterial drugs are not easily passed through lipid cell membranes, mainly distributed in blood and body fluids, and their apparent volume of distribution (Vd) is generally small;

Lipophilic antibacterial drugs are mainly distributed in adipose tissue and easily enter the cell through the cell membrane.

According to the "Expert Consensus on the Clinical Application of Antimicrobial Pharmacokinetics/Pharmacodynamic Theory" [1], the distribution of antibacterial drugs in different tissues is summarized and sorted out into 7 tables.

1

In the lower respiratory tissues

Macrolides, quinolones, tigecycline, and linezolid are concentrated in the respiratory epithelial lining at higher concentrations than in the blood drug.

Table 1 Commonly used antibacterial drugs in alveolar epithelial lining fluid concentration/blood concentration

It can be seen that the concentration of quinolones in the bronchial mucosa or secretions is higher than the concentration of the blood drug, while the concentration of β-lactam drugs in the bronchial mucosa or secretions is lower than 50% of the blood concentration.

Table 2 Bronchial mucosal or secretion concentrations/blood concentrations of commonly used antimicrobials

Macrolides and quinolones are found in high concentrations in alveolar macrophages, while drugs such as β-lactams and aminoglycosides have difficulty entering cells.

Table 3 Alveolar macrophage concentrations/blood concentrations of commonly used antimicrobial drugs

Antimicrobials with higher concentrations of lung tissue distribution are selected, with macrolides, quinolones, or tetracyclines to treat infections with atypical pathogens such as Legionella, Mycoplasma, and Chlamydia.

Linezolid is recommended when MRSA vancomycin MIC > 1 mg/L is required. Daptomycin is easily inactivated by alveolar surfactant in the lungs and cannot be used to treat lung infections.

2

In central nervous system (CNS) tissues

The distribution of anti-infective drugs in the CNS depends not only on the relative molecular mass, charge, lipophilicity, plasma protein binding rate of the blood-brain barrier, etc., but also on the host's own factors.

Table 4 Common antimicrobial cerebrospinal fluid/blood drug concentrations

Note: a can not yet reach the therapeutic concentration of Pseudomonas aeruginosa meningitis; b can not reach the treatment concentration of highly resistant penicillin Streptococcus pneumoniae meningitis; c imipenem is easy to cause convulsions and other adverse reactions are prudent to use for CNS infection; d can be injected intrathecal drugs.

Antibacterial drugs with higher concentrations in cerebrospinal fluid: third and fourth generation cephalosporins, aztrenam, carbapenems, sulfonamides, quinolones, vancomycin, rifampicin and isoniazid have higher penetration of the blood-brain barrier and higher concentrations in cerebrospinal fluid, and the above drugs can be selected for single or combined therapy with reference to the susceptibility test results of pathogenic bacteria.

3

In the abdominal tissue

Penicillins, cephalosporins, β-lactamase inhibitor combinations, quinolones, carbapenems, metronidazole, and vancomycin are concentrated in ascitic fluid.

Table 5 Concentrations of antibacterial drugs in the abdominal tissue

Selection of antimicrobial agents with higher intraperitoneal distribution concentrations: when empiric therapy requires coverage of Escherichia coli and Klebsiella pneumoniae, drugs with high concentrations of peritoneal tissues such as piperacillin/tazobactam, ticarcillin/clavulanate, and ceftazidime can be selected.

4

In the bloodstream

The distribution of commonly used antibacterial drugs in the bloodstream can be considered by considering the drug Vd and protein binding rate (PB), when the drug Vd is smaller, the higher the PB, indicating that the drug penetrates slower into the tissue, the blood concentration is high, the residence time is long, and the better the effect on bloodstream infection.

Drugs with higher Vd are quinolones and macrolides;

Vd centered are metronidazole, doxycycline, and linezolid;

The lower Vd are penicillins, cephalosporins, β-lactamase inhibitor combinations, carbapenems, vancomycin and daptomycin.

Drugs with high PB are benzoxicillin, cefoperazone, cefazolin, ceftriaxone, doxycycline, teicoplanin, and daptomycin;

PB centered are ticarcillin and vancomycin;

The lower PB is some penicillins, cephalosporins, β-lactamase inhibitor combinations, carbapenems, quinolones, metronidazole, and linezolid.

Considering Vd and PB, the blood concentrations of benzoxicillin, ticarcillin, cefazoline, ceftriaxone, daptomycin and vancomycin are higher, stay in plasma for a longer time, and have a better effect on bloodstream infections.

5

In the skin and soft tissues of the skin

Generally, lipophilic antibacterial drugs often have higher skin and skin soft tissue permeability than hydrophilic antibacterial drugs, and the ratio of the area under the curve (AUC) to plasma AUC of hydrophilic antibacterial drugs is lower than that of lipophilic drugs.

Common hydrophilic antimicrobials are β-lactams, aminoglycosides, glycopeptides, polymyxins, and fluconazole.

Common lipophilic antimicrobials are quinolones, macrolides, lincomycin, and tigecycline. Linezolid is a moderate lipophilic antibacterial drug.

When sepsis is concomitant, the distribution of lipophilic antimicrobials is less affected and generally does not require dose adjustment, but the Vd of hydrophilic antimicrobials is more influential and requires dose adjustment.

Antimicrobials with high concentrations and permeability in the skin and soft tissues, such as gatifloxacin, linezolid, and levofloxacin, can be selected.

6

Distribution in the urinary system

Bacterial lower urinary tract infections should be selected with sensitive antibacterial drugs with high concentrations in the urine; in the case of bacterial upper urinary tract infections, it is necessary to ensure a high concentration in both the urine and blood because it may be accompanied by bloodstream infections.

Table 6 Urinary tract infections commonly used antimicrobial drugs with prototype excretion rates from the urine

Whether the prototype of the antibacterial drug or its active ingredient is excreted through the urinary system is an important factor in the selection of antibacterial drugs in the urinary system.

Most quinolones and β-lactams have high plasma and urine concentrations and can be used to treat upper and lower urinary tract infections. The high urine concentrations of levofloxacin and ciprofloxacin in quinolones are not recommended, as the concentration in its urine is not high.

Β-lactams have higher concentrations in the urine of second-generation cephalosporins (cefuroxime, ceftiam); some third-generation cephalosporins and fourth-generation cephalosporins have anti-Pseudomonas species activity (ceftazidime, cefpiramides) in addition to higher concentrations in the urine.

Drugs such as nitrofurantoin and fosfomycin have very high concentrations in the urine, but because of their low blood concentrations, they are only used to treat lower urinary tract infections.

The antibacterial activity of fosfomycin increases with the decrease of urine pH, and when the urine pH decreases to 6.0, the sensitivity of bacteria to fofomycin increases significantly.

7

Distribution of antibacterial drugs in bone and joint tissues

Antimicrobials that can achieve effective therapeutic concentrations in bone and joint tissues include lincomycin, clindamycin, fosfomycin, quinolones, and vancomycin, while high-dose penicillins and cephalosporins can also achieve concentrations.

Table 7 Commonly used antibacterial drugs in bone tissue concentrations

Fight against infection in bone and joint tissue sites: high concentrations of bactericidal agents in bone and joint tissue with fast onset of action should be selected and given adequate doses.

Monotherapy such as penicillins, lincomycin, clindamycin, and quinolones is susceptible to drug resistance. In clinical use, it can be combined with other drugs, and in order to ensure the bactericidal concentration in the blood and bone tissue, intravenous infusion should be given during initial treatment.

In the treatment of diabetic foot, daptomycin 6 mg / kg, 1 time / day, after administration 3 hours of tissue and bone concentration has reached a higher concentration at this dose, can effectively treat MRSA and coagulase-negative staphylococcus and β-hemolytic streptococcus caused osteoarticular infections.

High-dose penicillins and cephalosporins can also be found in blood and bone-joint infections.