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Pharmacology

Infections

Question 178 of 180

Regarding phenoxymethylpenicillin (penicillin V), which of the following statements is CORRECT:

Answer:

Phenoxymethylpenicillin (penicillin V) is less active than benzylpenicillin but has a similar antibacterial spectrum. It is gastric-acid stable and therefore suitable for oral administration, but should not be used for serious infections because absorption can be unpredictable and plasma concentrations variable. It is given primarily for respiratory tract infections in children, for streptococcal tonsillitis and for continuing treatment after one or more injections of benzylpenicillin when clinical response has begun. It is also used for prophylaxis against streptococcal infections following rheumatic fever and against pneumococcal infections following splenectomy or in sickle-cell disease. It should not be used for meningococcal or gonococcal infections.

Penicillins

Mechanism of Action

Penicillins are beta-lactam antibiotics that inhibit bacterial cell wall synthesis by inactivating bacterial transpeptidases and preventing the cross-linking of peptidoglycan polymers that is essential for bacterial cell wall integrity. This results in loss of rigidity and a susceptibility to rupture. The major cause of resistance is the production of beta-lactamases (penicillinases) that are produced by certain strains of bacteria.

Penicillins diffuse well into body tissues and fluids, but penetration into the cerebrospinal fluid is poor except when the meninges are inflamed.

Side Effects

Common side effects include: Anaphylaxis; angioedema; diarrhoea (very common, occurs most commonly with broad-spectrum antibiotics, may be associated with colitis); fever; hypersensitivity reactions; joint pains; rashes; serum sickness-like reaction; urticaria

Rare side effects include: Cerebral irritation (may result from excessively high doses or in patients with severe renal failure); CNS toxicity (including convulsions); coagulation disorders; encephalopathy; haemolytic anaemia; interstitial nephritis; leucopenia; thrombocytopenia

Allergy

The most important side effect of the penicillins is hypersensitivity which can be fatal.

Penicillin allergy is a potentially serious adverse reaction which can be life threatening. It is the most commonly noted drug allergy in the UK, reported by about 10% of the population. It is estimated, however, that only around 20% of those reporting penicillin allergy are truly allergic.

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.

Patients with a history of a more minor rash (i.e. non-confluent, non-pruritic rash restricted to a small area of the body) or delayed reaction (rash occurring more than 72 hours after penicillin administration), may not be truly allergic and may be considered for penicillin or beta-lactam treatment in severe infection (although possibility of allergy should be borne in mind). Other beta-lactam antibiotics (including cephalosporins) can be used in these patients.

Indications

First Line Antibiotic Indications
Ampicillin or amoxicillin Blind therapy for native valve endocarditis; endocarditis caused by enterococci (with low-dose gentamicin); endocarditis caused by HACEK organisms (with low-dose gentamicin); blind treatment of meningitis in adults > 50 years (with cefotaxime/ceftriaxone); meningitis caused by Listeria (with gentamicin); otitis media; sinusitis; oral infection; exacerbation chronic bronchitis; low-severity community acquired pneumonia; moderate-severity community acquired pneumonia (with clarithromycin)
Co-amoxiclav Severe or resistant otitis media; resistant sinusitis; severe or resistant dental infection; high-severity community acquired pneumonia (with clarithromycin); hospital acquired pneumonia (non severe signs or symptoms and not at higher risk of resistance); animal and human bite wounds
Flucloxacillin Native valve endocarditis caused by staphylococci; prosthetic valve endocarditis caused by staphylococci (with rifampicin and low-dose gentamicin); spreading/severe otitis externa; osteomyelitis; septic arthritis; widespread impetigo; severe erysipelas; cellulitis; mastitis during breastfeeding
Benzylpenicillin Meningococcal disease (prehospital); endocarditis caused by streptococci (with or without low-dose gentamicin); endocarditis caused by enterococci (with low-dose gentamicin); meningitis caused by meningococci; erysipelas
Phenoxymethylpenicillin Erysipelas, acute tonsillitis
Piperacillin/tazobactam Community acquired septicaemia, hospital acquired septicaemia; peritonitis; hospital acquired pneumonia (severe signs or symptoms or at higher risk of resistance); complicated infections involving the urinary tract, skin and soft tissues, or intra-abdomen

Benzylpenicillin

Benzylpenicillin sodium remains an important and useful antibiotic but is inactivated by bacterial beta-lactamases. It is effective for many streptococcal (including pneumococcal), gonococcal, and meningococcal infections and also for anthrax, diphtheria, gas-gangrene, and leptospirosis. Pneumococci, meningococci, and gonococci which have decreased sensitivity to penicillin have been isolated; benzylpenicillin sodium is no longer the drug of first choice for pneumococcal meningitis. Although benzylpenicillin sodium is effective in the treatment of tetanus, metronidazole is preferred. Benzylpenicillin is inactivated by gastric acid and absorption from the gastrointestinal tract is low; therefore it must be given by injection.

If meningococcal disease (meningitis with non-blanching rash or meningococcal septicaemia) suspected, benzylpenicillin sodium should be given before transfer to hospital, so long as this does not delay the transfer. If a patient with suspected bacterial meningitis without non-blanching rash cannot be transferred to hospital urgently, benzylpenicillin sodium should be given before the transfer.

Phenoxymethylpenicillin

Phenoxymethylpenicillin (penicillin V) is less active than benzylpenicillin but has a similar antibacterial spectrum. It is gastric-acid stable and therefore suitable for oral administration, but should not be used for serious infections because absorption can be unpredictable and plasma concentrations variable.

It is given primarily for respiratory tract infections in children, for streptococcal tonsillitis and for continuing treatment after one or more injections of benzylpenicillin when clinical response has begun. It is also used for prophylaxis against streptococcal infections following rheumatic fever and against pneumococcal infections following splenectomy or in sickle-cell disease. It should not be used for meningococcal or gonococcal infections.

Flucloxacillin

Flucloxacillin is unique in that it is beta-lactamase stable and it can be used in infections caused by beta-lactamase producing staphylococci e.g. S. aureus. It is acid-stable and can therefore be given by mouth as well as by injection.

It is used first line for treatment of widespread impetigo infection, cellulitis, mastitis, osteomyelitis, septic arthritis, severe erysipelas, severe/spreading otitis externa and infective endocarditis caused by staphylococci.

The most common adverse effects of flucloxacillin include nausea, vomiting, skin rash, and diarrhoea. Cholestatic jaundice and hepatitis may occur very rarely, up to two months after treatment with flucloxacillin has been stopped. Administration for more than 2 weeks and increasing age are risk factors.

Ampicillin

Ampicillin is active against certain Gram-positive and Gram-negative organisms but is inactivated by penicillinases. Ampicillin is associated with high levels of resistance, therefore it is often not appropriate for blind treatment of infection. It is principally indicated for the treatment of exacerbations of chronic bronchitis and middle ear infections, both of which may be due to Streptococcus pneumoniae and H. influenzae, and for urinary tract infections.

Maculopapular rashes commonly occur with ampicillin (and amoxicillin) but are not usually related to true penicillin allergy. They almost always occur in patients with glandular fever; thus broad-spectrum penicillins should not be used for blind treatment of a sore throat. The risk of rash is also increased in patients with acute or chronic lymphocytic leukaemia or in cytomegalovirus infection.

Amoxicillin

Amoxicillin is a derivative of ampicillin and has a similar antibacterial spectrum. It is better absorbed than ampicillin when given orally, producing higher plasma and tissue concentrations; unlike ampicillin, absorption is not affected by the presence of food in the stomach. The adverse effects of amoxicillin are mainly gastrointestinal and mild and include nausea, vomiting and diarrhoea.

Amoxicillin is used first line for low to moderate severity community acquired pneumonia, exacerbations of chronic bronchitis, for acute otitis media, for acute sinusitis, for oral infections/dental abscess, for Listeria meningitis (in combination with another antibiotic), for infective endocarditis (in combination with another antibiotic) and for H. Pylori eradication (in combination with metronidazole/clarithromycin and a proton pump inhibitor).

Co-amoxiclav

Co-amoxiclav consists of amoxicillin with the beta-lactamase inhibitor clavulanic acid. Clavulanic acid itself has no significant antibacterial activity but, by inactivating beta-lactamases, it makes the combination active against beta-lactamase-producing bacteria that are resistant to amoxicillin. These include resistant strains of Staph. aureus, E. coli, and H. influenzae, as well as many Bacteroides and Klebsiella spp, causing infections such as respiratory tract infections, bone, joint and soft tissue infections, genitourinary and abdominal infection. Co-amoxiclav should be reserved for infections likely, or known, to be caused by amoxicillin-resistant beta-lactamase-producing strains.

The most common adverse effects of co-amoxiclav include nausea, vomiting, skin rash and diarrhoea. Pseudomembranous colitis should be considered if a person develops severe diarrhoea during or after treatment with co-amoxiclav. Cholestatic jaundice can occur either during or shortly after the use of co-amoxiclav. An epidemiological study has shown that the risk of acute liver toxicity was about 6 times greater with co-amoxiclav than with amoxicillin. Cholestatic jaundice is more common in patients above the age of 65 years and in men; these reactions have only rarely been reported in children. Jaundice is usually self-limiting and very rarely fatal.

Antipseudomonal Penicillins

Piperacillin, a ureidopenicillin, is only available in combination with the beta-lactamase inhibitor tazobactam. Ticarcillin, a carboxypenicillin, is only available in combination with the beta-lactamase inhibitor clavulanic acid. Both preparations have a broad spectrum of activity against a range of Gram-positive and Gram-negative bacteria, and anaerobes. Piperacillin with tazobactam has activity against a wider range of Gram-negative organisms than ticarcillin with clavulanic acid and it is more active against Pseudomonas aeruginosa. These antibacterials are not active against MRSA. They are used in the treatment of septicaemia, hospital-acquired pneumonia, and complicated infections involving the urinary tract, skin and soft tissues, or intra-abdomen. For severe pseudomonas infections these antipseudomonal penicillins can be given with an aminoglycoside (e.g. gentamicin) since they have a synergistic effect.

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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

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