Five generations of cephalosporins – super-complete usage comparison, and precautions!

Cephalosporin antibacterial drugs are semi-synthetic antibacterial drugs synthesized by connecting the parent nucleus of cephalosporins with different side chains (7-ACA), and are the most widely used β-lactam antibacterial drugs

Concise comparison of the first and fifth generations of cephalosporin

Due to the variety of cephalosporins, the indications, antibacterial profiles, stability and adverse reactions of β-lactamase of each drug are not the same, which is easy to cause confusion and confusion, so we first make a simple comparison of the five generations of cephalosporins to facilitate memory

Table 1: Representative drugs of the fifth generation of cephalosporins

Clinically, there are also commonly used cefxitins, cefminol classified as the second generation; Laoxycephalosporin belongs to the third generation

Table 2: Antimicrobial profiles, enzyme stability and nephrotoxicity of five generations of cephalosporins

Second, the first generation of cephalosporins pharmacological characteristics

The first generation of cephalosporins was introduced in the early 1960s, mainly acting on aerobic gram-positive (G+) coccidioides, and only a small number of gram-negative (G-) bacillus have certain antibacterial activity

However, the resistance of the first generation of cephalosporin to the β-lactamase of G-bacteria is weak, it is easier to resist drugs, and the stability of the enzyme is not as good as that of the second and third generations

It is mainly used for respiratory tract, urinary tract, skin and soft tissue infections

Table 3: Pharmacological characteristics of first-generation cephalosporins

Third, the second generation of cephalosporin pharmacological characteristics

Compared with the first generation of cephalosporins, the antibacterial effect of the second generation of cephalosporins on G+ bacteria was slightly weakened, but the antibacterial effect and enzyme stability of G- bacteria were enhanced, and the nephrotoxicity was relatively small

It is commonly used to treat respiratory tract, biliary tract, intestinal urinary tract and soft tissue, bone and joint, obstetrics and gynecology infections

Table 4: Pharmacological characteristics of second-generation cephalosporins

Fourth, the pharmaceutical characteristics of the third generation of cephalosporins

The third generation of cephalosporins is a broad-spectrum antibacterial drug, its anti-G- bacteria activity is stronger (the antibacterial spectrum covers Pseudomonas aeruginosa), the effect on G+ bacteria is not as good as the first and second generations, and the β-lactamase is more stable, basically no nephrotoxicity

Clinically, it is mainly used for serious infections caused by sensitive bacteria such as urinary tract, respiratory tract, meningitis, sepsis and other infections

Table 5: Pharmacological characteristics of third-generation cephalosporins

Fifth, the fourth generation of cephalosporin pharmacological characteristics

Fourth-generation cephalosporin anti-G+ activity is similar to ceftriaxone, and anti-G-bacterial activity (including Pseudomonas aeruginosa) is similar to ceftazidime, which is more stable for β-lactamase but slightly less

Clinically, it is mainly used for various serious infections such as respiratory tract infections, urinary tract infections, biliary tract infections, sepsis, etc.

Table 6: Pharmacological characteristics of fourth-generation cephalosporins

Sixth, the fifth generation of cephalosporin pharmacological characteristics

Fifth-generation cephalosporins currently have only two types:

Currently, it is clinically approved for the treatment of community-acquired pneumonia and complex skin and skin tissue infections, including MRSA

Table 7: Pharmacological characteristics of fifth-generation cephalosporins

Seven and five generations of cephalosporin indications

Nephrotoxicity of the eighth and fifth generations of cephalosporin

Fifth generation (almost nothing) = fourth generation (little) < third generation (small) < second generation (smaller) < second generation (larger)

Cephalosporin antibiotics are mainly excreted by the kidneys, and patients with moderate or greater renal insufficiency should adjust the dose

The nephrotoxicity of the first generation of cephalosporins is large, and the combination with diuretics and aminoglycosides may aggravate the nephrotoxicity of the former, and attention should be paid to monitoring renal function

In moderate or above hepatic hypofunction, cefoperazone and ceftriaxone may need to be adjusted in dose
.

9.
Acute bacterial meningitis

Antibacterial drugs that easily cross the blood-brain barrier are selected, and if necessary, they are combined, and are generally administered intravenously at the maximum therapeutic dose
.

Ampicillin has excellent activity against Listeria mononuclearum, a cause of meningitis in immunocompromised patients
.

Ceftriaxone easily penetrates the blood-brain barrier, cefotaxime easily penetrates the inflamed meninges, and meropenem can achieve an effective concentration
in cerebrospinal fluid.

10.
Varieties that need to be tested

1.
The specification requires the variety of skin test

Ceftiam, cefmexime, cefminol sodium, ceftiazole sodium, cefotaxime sodium sulbactam sodium, cefotaphene sodium, etc
.

2.
Cross allergies between cephalosporins

Cefazolin, cefofuroxime, and cefotiam have the lowest similarities to other cephalosporin antibiotics, but cefotiam must be tested
in the skin.

3.
Cross allergy with penicillins

The incidence of cross-allergic reactions between first-generation cephalosporins and penicillins is about 4%;

The incidence of cross-allergic reactions between second-generation cephalosporins and penicillins is about 1%;

Third- and fourth-generation cephalosporins differ from penicillin-like side chains, and cross-allergic reactions are rare
.

11.
Disulfiram-like reaction

1.
Main mechanism

Inhibits the activity of acetaldehyde dehydrogenase, so that acetaldehyde accumulates in the blood, disulfiram-like reactions occur, facial flushing, headache, dizziness, abdominal pain, stomach pain, nausea, vomiting, rapid heartbeat, shortness of breath, chest tightness, decreased blood pressure, drowsiness, hallucinations, etc
.

2.
Represents the drug

The structure contains thiometrizozole groups of cephalosporin antibiotics, such as cefmendo, cefnixi, ceftiam, cefoperazone, cefomexime, cefpiramide, cefametazole, cefrazine, ceftitan, cefminol, laxercephalosporin, fluoxy cephalosporin and so on
.

Cephalosporin antibiotics without thiophotrezole groups in the molecule, such as ceftriaxone, cefazoline, cefotaxime, ceftazidime, ceftaxin, cefaclos, etc.
, can also cause disulfiram-like reactions
.
The mechanism of action needs to be further studied
.

11.
Be wary of cephalosporin encephalopathy

Mainly associated with antagonistic inhibitory transmitter γ-aminobutyric acid binding to receptors
.
Presents with hyperinstaticism, hallucinations, mania, limb tremors, and even induced epileptic or psychotic seizures
.

Patients with chronic renal insufficiency are susceptible to cephalosporin encephalopathy
.
Dicitracheal excretion of cefoperazone hepatic and renal channels, rarely causing antibiotic encephalopathy; 90% of cefotaxime and ceftazidime are excreted by the kidneys and should be avoided in patients with
chronic renal insufficiency.

Although ceftriaxone is excreted through the liver and kidney double channel, due to its good tissue permeability, it is easy to pass through the blood-brain barrier and also easily cause cephalosporin encephalopathy
.
Retrospective analysis found that cefepime caused the largest number of cases of encephalopathy, which may be related to almost all of its excretion through the kidneys
.

Resources:

[1] He Lixian et al.
National guidelines for antimicrobial therapy[M].
Beijing: People's Medical Publishing House, 2017: 342 pp.

Sanford Guidelines for Antimicrobial Therapy[M].
Beijing: Peking Union Medical College Press, 2017: 273 pp.

The difference between five generations of cephalosporins[J].
Health Management, 2017(12): 93-95.

Li Tongzeng.
Cephalosporin family generational view[J].
Physician Online, 2016, 6(19): 14-15.

[5] Sixteen cephalosporins are characterized and prescribed for administration,