Jan, 2001. Intravenous antibiotics [online]. Seacroft and St James's University Hospitals, Leeds, UK. Available from http://www.cysticfibrosismedicine.com

There are four main indications for intravenous antibiotic therapy.

1) To eradicate early Pseudomonas aeruginosa infection as an alternative to oral ciprofloxacin and nebulised Colomycin, or where this treatment has failed.

2) To treat a new cough that has not settled with the addition of an oral antibiotic.

3) To treat a respiratory exacerbation

4) As a routine three-monthly treatment for patients with chronic Pseudomonas aeruginosa infection.

Eradication of early Pseudomonas aeruginosa infection: The standard treatment for the first Pseudomonas aeruginosa isolate, or for intermittent and infrequent Pseudomonas aeruginosa isolates, is a course of oral ciprofloxacin and nebulised colistin, (Frederiksen et al, 1997). If this treatment fails to eradicate this Pseudomonas aeruginosa infection we would try a two week course of intravenous anti-pseudomonal antibiotics in combination with nebulised colistin. In young children where there is difficulty in getting good compliance with oral ciprofloxacin and nebulised colistin, it would be reasonable to go straight to a two week course of intravenous anti-pseudomonal antibiotics, if possible with nebulised colistin.

The new cough: Many mildly affected patients are treated with intravenous antibiotics if they develop a new cough which has persisted despite additional oral antibiotic therapy (excluding other causes for cough eg asthma, nasal drip, smoking, reflux etc) . There is commonly an impressive response to intravenous treatment.

Treatment of a respiratory exacerbation: Respiratory exacerbations are loosely defined in terms of more breathlessness, increased cough, change in sputum colour to more yellow or green, changes on chest x-ray, and loss of appetite. The reported increased severity of two or more lower respiratory tract symptoms and a fall of 10% or more from baseline FEV1 or FVC often best reflects a new respiratory exacerbation (Pond & Conway, 1996).

Elective intravenous antibiotic therapy: There is abundant evidence that intravenous antibiotics are effective in the treatment of exacerbations of chest infection due to Pseudomonas and other pathogens (Smith et al, 1988; Regelmann et al, 1990). Patients chronically infected by P. aeruginosa may be given regular three-monthly courses of I.V. antibiotics to reduce the amount of bacterial infection within the airways. This is considered preferable to waiting for the respiratory infection to progress to a stage when the patient is obviously unwell and has increasing symptoms and signs. The Copenhagen CF Centre has demonstrated improved outlook for patients chronically infected with P. aeruginosa by the policy of regular three monthly treatments (Jensen et al, 1989; Frederiksen et al, 1996). There are obvious problems with such a policy, not least a severe interference with the patient's and family's life style. This can be minimised by teaching the family and/or patient to administer the treatment at home. The policy of frequent ward admissions also increases the opportunities for cross infection as the patient spends two months of every year in hospital with other chronically infected CF patients (Jensen et al, 1989). Outbreaks of multi-resistant organisms have been described with such a policy in Copenhagen (Pedersen et al, 1986). Finally, there is the cost of treatment to the hospital and health service and the extra costs incurred by hospitalisation for the patient and relatives. These problems have stimulated the development of home intravenous antibiotic treatment. Many of the units in the UK have taken up this regimen of treatment with intravenous anti-pseudomonal antibiotics every three months. Unfortunately, its value has never been proven in a controlled trial and is now unlikely to be so as the data from Copenhagen are so persuasive. It is the Leeds practice that the advantages and disadvantages of a regular three monthly intravenous antibiotic programme are eplained to the patient and parents so that they can come to their own decisions. If asked to advise, we would be in favour of this regimen of treatment.

Treatment as an inpatient: It is important to stress that the "hospital treatment package" includes removal from the home environment (where there may be exposure to cigarette smoke!), rest, temporary transfer of the responsibility of treatment from the patient/family to the hospital staff, expert dietary advice, regular meals with possible increased compliance with pancreatic enzymes and vitamin supplements. These are additional advantages over and above the regular professional physiotherapy and intravenous antibiotics.

Duration of antibiotics and which one should be used: The duration of a course of intravenous antibiotic therapy varies but is usually about 2 weeks. The frequency of courses varies between patients. Some may require four or more courses a year and others only an occasional course every year or so. Some will remain stable for years without further iv treatment. Usually an aminoglycoside is combined with a ureidopenicillin or beta lactam. Using two antibiotics decreases the risk of antibiotic resistance developing (Cheng et al, 1996). Choice of antibiotics will depend on the sensitivities of the organisms. A significant number of patients have drug allergies and a clear past drug history should be taken. In the event of recent sputum results being unavailable then treatment should be based on the last sputum sensitivities and adapted at a later date if necessary. In the event of a multi-resistance or poor clinical response standard combination therapy is used and alternated according to response. Tobramycin and piperacillin, or tobramycin and ceftadizime, are popular combinations. Imipenem, meropenem, aztreonam, and colomycin (Conway et al, 1997) are also used intravenously, depending on the organisms and their sensitivities. Colomycin should remain a second line antibiotic and substituted for tobramycin in the event of antibiotic resistance or tobramycin allergy/side effect. The use of colomycin in combination with tobramycin is not usually given due to possible renal toxicity. In retrospective and prospective studies once daily tobramycin appears to be as effective and safe as thrice daily administration (Whitehead et al, 1996; Whitehead et al, 1999). Results of a larger study are awaited. Once daily dosage is more convenient and preferred by patients. Close monitoring is essential and trough levels should be <1 mg/litre. Oral probenecid should be added to the regimen when using Piperacillin or Azlocillin. Imipenem and Meropenem are potent B-lactamase inducers. Avoid use with Piperacillin, Ceftazidime and Aztreonam. Studies indicate that ceftazidime is as effective when given as two rather than three doses each day - an added convenience particularly for patients on home treatment (Conway, 1996). It is important to use two antibiotics, as monotherapy may result in resistant organisms (Cheng et al, 1996; Denton et al, 1996).

Response to antibiotic therapy: Improvement during a course of iv treatment can be demonstrated by performing regular respiratory function tests and carefully assessing other signs including body weight. In Leeds a record of daily clinical score is kept to monitor the details of progress particularly sputum volume and colour, cough, wheeze, temperature and respiratory rate (Conway et al, 1985). Pan-resistant bacteria should be treated with the antibiotics that by experience have produced the best clinical response in that individual patient. When several different Pseudomonas types are cultured from the same sputum sample, each with a differing antibiotic sensitivity pattern, the antibiotic combination used should cover all strains as far as this is possible. Clinical improvement is found even with treatment with antibiotics to which the bacteria have shown in vitro resistance. This may be due to anti-inflammatory and/or antioxidant effects (Adeboyeku et al, 1999; Ledson et al, 1999). Multiple combinations of antibiotics might be of benefit in treating resistant B. cepacia infection through synergistic interaction, e.g. meropenem-tobramycin, meropenem-ceftazidime. When triple therapy is given, e.g. meropenem-tobramycin-ceftazidime, growth of another micro-organism is frequently found (Aaron et al, 1999).

The Leeds philosophy: The frequent and early use of intravenous antibiotics is probably the most important factor in maintaining the improved condition of many patients. Reluctance to treat with every available means as vigorously as possible contributes to the deterioration of the chest condition in some patients. If in doubt treat and review the patient's response in detail as described. The improvement usually fully justifies the more intensive treatment.

For more details see CF (UK) Trust antibiotic consensus section

References

Adeboyeku DU, Burgess JC, Hodson ME. Antibiotic sensitivity and clinical outcome of acute respiratory exacerbations in adult CF patients colonised with P. Aeruginosa. Pediatr Pulmonol 1999; Suppl 19: 264

Aaron SD, MacDonald N, Ferris W. Multiple combination bactericidal antibiotic testing for CF exacerbations caused by Burkholderia cepacia organisms. Pediatr Pulmonol, 1999; Suppl 19; 270.

Conway SP, Pond MN, Watson AJ, Etherington C, Goldman MH. Robey H. Intravenous colistin sulphamethate in acute respiratory exacerbations in adult patients with cystic fibrosis. Thorax 1997; 52: 987-993

Cheng K, Smyth RL, Govan JRW, Doherty C, Winstanley C, Denning N, et al. Spread of B-lactam-resistant Pseudomonas aeruginosa in a cystic fibrosis clinic. Lancet 1996; 348: 639-642

Denton M, Todd NJ, Littlewood JM. Role of anti-pseudomonal antibiotics in the emergence of Stenotrophomonas maltophilia in cystic fibrosis patients. Eur J Clin Microbiol Infect Dis 1996; 15: 402-405

Frederiksen B, Koch C, Hoiby N. Antibiotic treatment at time of initial colonisation with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration in pulmonary function in patients with cystic fibrosis. Pediatr Pulmonol 1997; 23: 330-335

Jensen T, Pedersen SS, Hoiby N, Koch C, Flensborg EW. Use of antibiotics in cystic fibrosis. The Danish approach. Antibiot Chemother 1989;42: 237-246

Ledson M, Gallagher MJ, Hart CA, Walshaw MJ. Differential effect of antibiotic therapy on colony counts and inflammatory markers in CF patients colonised with B. cepacia or P. aeruginosa. Pediatr Pulmonol 1999; Suppl 19: 274

Pedersen SS, Koch C, Hoiby N, Rosendal K. An epidemic spread of multiresistant Pseudomonas aeruginosa in a cystic fibrosis centre. J Antimicrob Chemother 1986; 17: 505-516

Pond MN, Conway SP. Towards a definition of pulmonary exacerbation for young adults with CF. Israel J Med Sci 1996; 32(Suppl): S243

Pond M, Carr I, Littlewood JM, Conway SP. A longitudinal study of anti-Pseudomonas aeruginosa ELISA in young adults with cystic fibrosis. 19th European Cystic Fibrosis Conference, Paris, 1994: p24

Regelmann WE, Elliott GR, Warwick WJ, Clawson CC. Reduction of sputum Pseudomonas aeruginosa density by antibiotics improves lung function in cystic fibrosis more than do bronchodilators and chest physiotherapy alone. Am Rev Respir Dis 1990; 141: 914--921

Smith AL, Redding G, Doershuk C, Goldman D, Gore E, Hilman B et al. Sputum changes associated with therapy for endobronchial exacerbation in cystic fibrosis. J Pediatr 1988; 112: 547-554

Whitehead A, Conway SP, Dave J. Once daily administration of tobramycin is an effective and safe treatment of acute respiratory exacerbations in adults with cystic fibrosis. Israel J Med Sci 1996; 323: S257

Whitehead et al. Efficacy and safety of once daily tobramycin in treating acute respiratory exacerbations in adult patients. The Netherlands J Med 1999; 54(Suppl): S36.

Copyright © cysticfibrosismedicine