Pharmacology
Infections
Regarding cephalosporin antibiotics, which of the following statements is INCORRECT:
Answer:
The principal side effect of the cephalosporins is hypersensitivity. Patients with a history of anaphylaxis, urticaria, or rash immediately after penicillin use should not receive a penicillin or other beta-lactam antibiotics; about 0.5 – 6.5 % of penicillin-sensitive patients will also be allergic to the cephalosporins.Cephalosporins
Pharmacology / Infections
Last Updated: 26th March 2019
Mechanism of Action
The cephalosporins are broad-spectrum beta-lactam antibiotics that attach to penicillin binding proteins to interrupt cell wall synthesis, leading to bacterial cell lysis and death.
They are used for the treatment of septicaemia, pneumonia, meningitis, biliary tract infections, peritonitis, and urinary tract infections. Cephalosporins penetrate the cerebrospinal fluid poorly unless the meninges are inflamed; cefotaxime and ceftriaxone are suitable cephalosporins for infections of the CNS (e.g. meningitis).
Side Effects
The principal side effect of the cephalosporins is hypersensitivity. Patients with a history of anaphylaxis, urticaria, or rash immediately after penicillin use should not receive a penicillin or other beta-lactam antibiotics; about 0.5 – 6.5 % of penicillin-sensitive patients will also be allergic to the cephalosporins.
Gastrointestinal effects such as diarrhoea, nausea and vomiting are common with cephalosporins. Antibiotic-associated colitis may occur, more commonly with second- and third-generation cephalosporins.
Cefalexin
The orally active first generation cephalosporin, cefalexin is useful for urinary tract infections which do not respond to other drugs or which occur in pregnancy, respiratory tract infections, otitis media, sinusitis, and skin and soft-tissue infections.
Cefuroxime
The second generation cephalosporin, cefuroxime is less susceptible than the earlier cephalosporins to inactivation by beta-lactamases. It is therefore active against certain bacteria which are resistant to the other drugs and has greater activity against Haemophilus influenzae.
Cefuroxime is indicated first line for community acquired septicaemia, early-onset hospital acquired pneumonia and acute pyelonephritis.
Cefotaxime and Ceftriaxone
The third generation cephalosporins, cefotaxime and ceftriaxone have greater activity than the second generation cephalosporins against certain Gram-negative bacteria e.g. N. gonorrhoeae, N. meningitidis. However, they are less active than cefuroxime against Gram-positive bacteria, most notably Staphylococcus aureus. Their broad antibacterial spectrum may encourage superinfection with resistant bacteria or fungi (e.g. C. difficile colitis).
Cefotaxime (or ceftriaxone) are indicated first line in:
- Blind treatment of meningitis in patients > 3 months (with amoxicillin if patient > 50 years)
- Meningitis caused by meningococci
- Meningitis caused by pneumococci
- Meningitis caused by H. influenzae
- Severe or invasive salmonellosis
- Typhoid fever
- Gonorrhoea
- Gonococcal arthritis
- Haemophilus influenzae epiglottitis
Ceftriaxone has a longer half-life and therefore needs to be given only once daily. The calcium salt of ceftriaxone forms a precipitate in the gallbladder which may rarely cause symptoms but these usually resolve when the antibiotic is stopped.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
