Chemical structure of Flucloxacillin.
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Flucloxacillin

Flucloxacillin (INN) or floxacillin (USAN) is a narrow spectrum beta-lactam antibiotic. It is used to treat infections caused by susceptible Gram-positive bacteria. Notably, it is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most penicillins. It is very similar to dicloxacillin and these two agents are considered interchangeable. Flucloxacillin is available under a variety of trade names including Flopen (CSL) and Floxapen (GSK). more...

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Mode of action

Like other β-lactam antibiotics, flucloxacillin acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of Gram-positive bacteria.

Medicinal chemistry

Flucloxacillin is insensitive to beta-lactamase (also known as penicillinase) enzymes secreted by many penicillin-resistant bacteria. The presence of the isoxazolyl group on the side chain of the penicillin nucleus facilitates the β-lactamase resistance, since they are relatively intolerant of side-chain steric hindrance. Thus it is able to bind to penicillin binding proteins (PBPs) and inhibit peptidoglycan crosslinking, but is not bound by or inactivated by β-lactamases.

Clinical use

Flucloxacillin is more acid-stable than many other penicillins and can be given orally, in addition to parenteral routes. However, like methicillin, it is less potent than benzylpenicillin against non-β-lactamase-producing Gram-positive bacteria.

Flucloxacillin has similar pharmacokinetics, antibacterial activity and indications to dicloxacillin and the two agents are considered interchangeable. It is believed to have higher incidence of severe hepatic adverse effects than dicloxacillin, but a lower incidence of renal adverse effects. (Rossi, 2006)

Available forms

Flucloxacillin is commercially available as the sodium salt flucloxacillin sodium, in capsules (250 or 500 mg), oral suspensions (125 mg/5 mL or 250 mg/5 mL), and injections (powder for reconstitution, 250, 500 and 1000 mg per vial).

Indications

Flucloxacillin is indicated for the treatment of infections caused by susceptible bacteria. Specific approved indications include: (Joint Formulary Committee, 2005; Rossi, 2006)

  • Staphylococcal skin infections and cellulitis – including impetigo, otitis externa, folliculitis, boils, carbuncles, and mastitis
  • Pneumonia (adjunct)
  • Osteomyelitis, septic arthritis
  • Septicaemia
  • Empirical treatment for endocarditis
  • Surgical prophylaxis

Flucloxacillin has relatively poor activity, as noted above, against non-β-lactamase-producing bacteria including Streptococcus pyogenes. Therefore empirical therapy for significant cellulitis often involves dual-therapy to cover both staphylococci and streptococci, using either penicillin or ampicillin in addition to flucloxacillin. The latter is available as a standardardised combination preparation co-fluampicil (flucloxacillin+ampicillin).

Precautions/contraindications

Flucloxacillin is contraindicated in those with a previous history of allergy to penicillins, cephalosporins or carbapenems. It should also not be used in the eye, or those with a history of cholestatic hepatitis associated with the use of dicloxacillin or flucloxacillin. (Rossi, 2006)

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Diagnosis challenge: how many did you get right?
From Diabetic Foot, The, 9/22/04 by Frank Webb

Below are the answers to the case studies provided by Consultant Podiatrist Frank Webb that featured on pages 145-146 of this issue.

Case study 1

Diagnosis

Hallux limitus affecting first metatarsal phalangeal joint with osteophyte formation and joint space narrowing, which has been present for a number of years. Incidence of a stress fracture in the past six to 12 months. On closer discussion with the patient, he informs that he had pain in the foot approximately nine months ago with no visible swelling but quite marked tenderness.

X-rays show a displaced fracture with bone callus formation and signs of bone healing of the second metatarsal. Due to the second metatarsal being displaced and shortened, increased pressure is put on and around the first metatarsal phalangeal joint, resulting in the increasing discomfort in this area.

Treatment

The hallux limitus could either be treated locally with orthotics to redistribute pressure, or with cortisone injections for symptomatic relief. Surgery would involve cheilectomy and/or fusion of the first metatarsal phalangeal joint.

Case study 2

Diagnosis

The extensive changes at the first metatarsal phalangeal joint and interphalangeal joint of the hallux are due to large punched-out erosions related to gout. A thick discharge was diagnosed as gouty tophi on microscopy. There is virtually total loss of the distal and intermediate phalanges of the fourth toe due to gouty erosions. Swabs were taken for culture and sensitivity of the wound, as well as samples of fluid to identify infecting bacteria. Bloods were taken to establish the status of his urate.

Treatment

Debridement of the gouty tophi from the ulcerated site to promote healing. Unfortunately, the patient was not a suitable candidate for allopurinol due to intolerance, so his water tablets were reduced to try and control the amount of fluid loss. Surgical shoes were provided to protect his feet. The patient re-ulcerated, however, due to gouty tophi, which then required debridement from the ulcerated site to promote healing. This was done after the soft tissue infection was controlled using intravenous antibiotics, namely flucloxacillin and amoxicillin in conjunction with metronidazole.

Case study 3

Diagnosis

There is a fusion to his first metatarsal phalangeal joint, osteoarthritis to the second metatarsal phalangeal joint, osteomyelitis affecting the third metatarsal with marked loss of the head and part of the base of the proximal phalanx of the third. Periosteal reaction is extending down the shaft. There is sequestra formation and the early formation of involucrum. Calcified vessels are also noted. There is some periosteal reaction at the base of the third phalanx also.

Magnetic resonance scans were used to show the level of bone oedema in order to give a good indication of the extent of the infected bone before surgery. STIR image is shown, which clearly demonstrates a cross-sectional view of the foot showing the third metatarsal to be white showing oedema (infection) whereas the other metatarsals appear grey.

Treatment

Patient was admitted for intravenous antibiotics (clindamycin and ciprofloxacin). The surgical procedure involved removal of a third ray under local anaesthetic after the draining of an abscess three days earlier.

Case study 4

Diagnosis

Fracture of calcaneus with osteomyelitis evident, with loss of bone and irregular cortex--early periosteal reaction.

Treatment

Treatment was to place the patient in a removable cast.

Attempts were made to address his glucose levels as well as his renal function. This was extremely difficult due to poor compliance, diet and lack of attention to restricted fluid intake. This caused problems with the amount of fluid retention in the foot.

He ultimately developed methicillin-resistant Staphylococcus aureus (MRSA), which was located in the bone on biopsy. The patient was taken to theatre for debridement of the osteomyelitic calcaneus, with a plan to take him at a later stage for fusion. At the time of debridement the wound was cleaned and packed with gentamicin beads as well as a Collatamp (gentamicin collagen dressing).

Initially the patient made good progress. He eventually went on to fixation of the calcaneus, which failed, and now awaits further surgery.

Frank Webb is Consultant Podiatrist in the Department of Podiatry and Foot Health, Hope Hospital, Salford

COPYRIGHT 2004 S.B. Communications
COPYRIGHT 2004 Gale Group

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