282
QUINOLONES IN ACUTE NON-TRAVELLERS’ DIARRHOEA Acute
gastrointestinal infections are common even developed countries. In the UK, for example, it can
in be calculated from survey datal that over 1 ’3 million adults and 800 000 children visit their general practitioner annually for proven or presumed infectious diarrhoea. Few patients have microbiological investigations, which explains the finding of pathogens in only 2-2% of episodes,! but bacteria are the likely cause in up to 35% of cases; viruses and protozoa account for the remainder. Until lately, the inherently different sensitivities of salmonellae, shigellae, campylobacter, and less common bacterial pathogens to oral antibiotics acted as a disincentive to antibiotic therapy for what is usually an acute self-limiting infection. Moreover, the clinical response to some antibiotics was unsatisfactory despite in-vitro activity,2 and the emergence of resistant strains was noted.3 There is also a tendency for overgrowth of other antibiotic-resistant bacteria because normal flora are suppressed by many antibiotics,4 and for salmonella carriage to be prolonged by treatment.5 Several new quinolones have in-vitro activity against all the common bacterial pathogens causing gastroenteritis,6 and clinical studies have shown that these agents do not suppress the anaerobic flora of the gut,7 so overgrowth of other organisms after treatment is rare. Resistance to quinolones occurs largely as a result of mutation.8 Plasmidmediated resistance to nalidixic acid has been reported only in Shigella dysenteriae type 1,9 is not widespread, and has not been demonstrated to the newer quinolones. Ciprofloxacin and norfloxacin have been extensively studied and found to be efficacious in both acute bacterial diarrhoea and travellers’ diarrhoea, and these agents successfully eradicate salmonellae and other bacterial pathogens.10-15 Thus some of the earlier arguments against antibiotic therapy cannot be used against these two compounds. In a double-blind trial in the USA in non-travellers’ diarrhoea, Goodman and colleagues have now shown a significantly better microbiological response with ciprofloxacin than with co-trimoxazole or placebo.16 However, the slight reduction in duration of diarrhoea did not reach significant levels in the group with proven bacterial pathogens, and further studies are needed. In the light of these data, what is the role of the new quinolones in the treatment of non-travellers’ diarrhoea? These agents are contraindicated in children, except under special circumstances. They are also expensive-eg, if every adult consulting a doctor in the UK for gastroenteritis was prescribed ciprofloxacin, the cost would be ;[24 million. The 13 000 kg that would be prescribed annually must also be expected to have an impact on microbial resistance. Ciprofloxacin-resistant campylobacter have been reported, but the mechanism of resistance was not identified,16 and mutation to ciprofloxacin resistance has also been reported in Salmonella typhimurium.17 In addition, some patients experience side-effects. There is a danger that some doctors will prescribe liberally, but in the absence of any data showing major economic benefits they should firmly resist this temptation. 3 years ago, Gorbach reviewed the treatment of bacterial diarrhoea in The Lancet and produced an algorithm showing when to obtain samples or consider antibiotic therapy .18 The newer quinolones will have a useful role for treatment of those adults identified in the algorithm. In addition,
of proven bacterial gastroenteritis in health care workers or those employed in catering should shorten absences from work. Quinolones also have an important role in the control of outbreaks in hospitals"’-21 and other institutions and in certain situations for the eradication of chronic salmonella carriage. 19 Controlled trials are needed, however, to compare the efficacy of the newer treatment
quinolones. 1. Office of
Population Censuses and Surveys. Morbidity statistics from general practice 1981-2. Third National Survey. Series MB5 No. 1. London. HM Stationery Office, 1986. 2. Levine MH, Antimicrobial therapy of infectious diarrhea. Rev Infect Dis 1986; 8 (suppl 2): S 207-16. 3. Murray BE. Resistance of shigella, salmonella and other selected enteric pathogens to antimicrobial agents. Rev Infect Dis 1986; 8 (suppl 2): S 172-82. 4. Van der Waaiz D. Colonization resistance of the
digestive tract: Clinical
consequences and implications. J Antimicrob Chemother 1982; 10: 263-70. 5. Nye FJ. Do antibiotics really prolong salmonella excretion? J Antimicrob Chemother 1981; 7: 215-16. 6. Finch RG, Gabbay FJ. The 6-fluoroquinolones: in vitro activity, pharmacokinetic behaviour and in vivo considerations. In: Quinolones-their future in clinical practice. R Soc Med Int Congr Symp Ser 1986; 104: 17-27. 7. Reeves D S. The effect of quinolone antibacterials on the gastrointestinal flora compared with that of other antibacterials. J Antimicrob Chemother 1986; 16: (suppl D): 89-102. 8. Piddock LVJ, Wise R. Mechanisms of resistance to quinolones and clinical perspectives. J Antimicrob Chemother 1989; 23: 475-83. 9. Munshi MH, Sack DA, Haider K, et al. Plasmid-mediated resistance to nalidixic acid in Shigella dysenteriae type 1. Lancet 1987; ii: 419-21. 10. Rogerie R, Ott D, Vandepitte J, et al. Comparison of norfloxacin and nalidixic acid for treatment of dysentery caused by Shigella dysenteriae in adults. J Antimicrob Chemother 1986; 29: 883-86. 11. Wang C, Sabbaj J, Corrado M, et al. World-wide clinical experience with norfloxacin: efficacy and safety. Scand J Infect Dis 1986; 48: (suppl) 81-89. 12. DuPont HL, Corrado ML, Sabbaj J. Use of norfloxacin in the treatment of acute diarrheal disease. Am J Med 1987; 82: S 79-83. 13. Ericsson CD, Johnson PC DuPont HL, et al. Ciprofloxacin or trimethoprim sulfamethoxazole as initial therapy for traveller’s diarrhea. Ann Intern Med 1987; 106: 216-20. 14. Pichler HET, Diridl G, Stickler K, Wolf D. Clinical efficacy of ciprofloxacin compared with placebo in bacterial diarrhea. Am J Med
1987; 82: 329-32. 15. Lolenkha S, Patanacharoen S. Clinical and microbiologic efficacy of norfloxacin for treatment of acute diarrhea. Rev Infect Dis 1988; 10: S 210-11. 16. Goodman LJ, Trenholme GM, Kaplan RL, et al. Empiric antimicrobial therapy of domestically acquired acute diarrhea in urban adults. Arch Intern Med 1990; 150: 541-46. 17. Piddock LVJ, Whale K, Wise R. Quinolone resistance in salmonella: clinical experience. Lancet 1990; 335: 1459. 18. Gorbach SL. Bacterial diarrhoea and its treatment. Lancet 1987; ii: 1378-82. 19. Damjanovic V, Willietts TH, Glynne Thomas D, et al. Eradication of salmonella by oral ciprofloxacin in food handlers. Lancet 1990; 335: 974. 20. Williams HMS, Richards J. Single-dose ciprofloxacin for shigellosis. Lancet 1990; 335: 1343-44. 21. Willocks LJ, Thompson C, Emmanuel FXS, et al. Hospital outbreak of Salmonella enteriditis infection treated with ciprofloxacin. Lancet 1990; 335: 1404-05.
REFLUX AND RESPIRATORY SYMPTOMS Much has been written about gastro-oesophageal reflux (GOR) and respiratory disorders since Kennedy’ first proposed an association almost 30 years ago. Numerous respiratory complaints have been attributed to acid reflux,2-4 but asthma has attracted most attention.5-10 Since reports with persuasive pathophysiological data in support of this
QUINOLONES IN ACUTE NON-TRAVELLERS’ DIARRHOEA Acute
gastrointestinal infections are common even developed countries. In the UK, for example, it can
in be calculated from survey datal that over 1 ’3 million adults and 800 000 children visit their general practitioner annually for proven or presumed infectious diarrhoea. Few patients have microbiological investigations, which explains the finding of pathogens in only 2-2% of episodes,! but bacteria are the likely cause in up to 35% of cases; viruses and protozoa account for the remainder. Until lately, the inherently different sensitivities of salmonellae, shigellae, campylobacter, and less common bacterial pathogens to oral antibiotics acted as a disincentive to antibiotic therapy for what is usually an acute self-limiting infection. Moreover, the clinical response to some antibiotics was unsatisfactory despite in-vitro activity,2 and the emergence of resistant strains was noted.3 There is also a tendency for overgrowth of other antibiotic-resistant bacteria because normal flora are suppressed by many antibiotics,4 and for salmonella carriage to be prolonged by treatment.5 Several new quinolones have in-vitro activity against all the common bacterial pathogens causing gastroenteritis,6 and clinical studies have shown that these agents do not suppress the anaerobic flora of the gut,7 so overgrowth of other organisms after treatment is rare. Resistance to quinolones occurs largely as a result of mutation.8 Plasmidmediated resistance to nalidixic acid has been reported only in Shigella dysenteriae type 1,9 is not widespread, and has not been demonstrated to the newer quinolones. Ciprofloxacin and norfloxacin have been extensively studied and found to be efficacious in both acute bacterial diarrhoea and travellers’ diarrhoea, and these agents successfully eradicate salmonellae and other bacterial pathogens.10-15 Thus some of the earlier arguments against antibiotic therapy cannot be used against these two compounds. In a double-blind trial in the USA in non-travellers’ diarrhoea, Goodman and colleagues have now shown a significantly better microbiological response with ciprofloxacin than with co-trimoxazole or placebo.16 However, the slight reduction in duration of diarrhoea did not reach significant levels in the group with proven bacterial pathogens, and further studies are needed. In the light of these data, what is the role of the new quinolones in the treatment of non-travellers’ diarrhoea? These agents are contraindicated in children, except under special circumstances. They are also expensive-eg, if every adult consulting a doctor in the UK for gastroenteritis was prescribed ciprofloxacin, the cost would be ;[24 million. The 13 000 kg that would be prescribed annually must also be expected to have an impact on microbial resistance. Ciprofloxacin-resistant campylobacter have been reported, but the mechanism of resistance was not identified,16 and mutation to ciprofloxacin resistance has also been reported in Salmonella typhimurium.17 In addition, some patients experience side-effects. There is a danger that some doctors will prescribe liberally, but in the absence of any data showing major economic benefits they should firmly resist this temptation. 3 years ago, Gorbach reviewed the treatment of bacterial diarrhoea in The Lancet and produced an algorithm showing when to obtain samples or consider antibiotic therapy .18 The newer quinolones will have a useful role for treatment of those adults identified in the algorithm. In addition,
of proven bacterial gastroenteritis in health care workers or those employed in catering should shorten absences from work. Quinolones also have an important role in the control of outbreaks in hospitals"’-21 and other institutions and in certain situations for the eradication of chronic salmonella carriage. 19 Controlled trials are needed, however, to compare the efficacy of the newer treatment
quinolones. 1. Office of
Population Censuses and Surveys. Morbidity statistics from general practice 1981-2. Third National Survey. Series MB5 No. 1. London. HM Stationery Office, 1986. 2. Levine MH, Antimicrobial therapy of infectious diarrhea. Rev Infect Dis 1986; 8 (suppl 2): S 207-16. 3. Murray BE. Resistance of shigella, salmonella and other selected enteric pathogens to antimicrobial agents. Rev Infect Dis 1986; 8 (suppl 2): S 172-82. 4. Van der Waaiz D. Colonization resistance of the
digestive tract: Clinical
consequences and implications. J Antimicrob Chemother 1982; 10: 263-70. 5. Nye FJ. Do antibiotics really prolong salmonella excretion? J Antimicrob Chemother 1981; 7: 215-16. 6. Finch RG, Gabbay FJ. The 6-fluoroquinolones: in vitro activity, pharmacokinetic behaviour and in vivo considerations. In: Quinolones-their future in clinical practice. R Soc Med Int Congr Symp Ser 1986; 104: 17-27. 7. Reeves D S. The effect of quinolone antibacterials on the gastrointestinal flora compared with that of other antibacterials. J Antimicrob Chemother 1986; 16: (suppl D): 89-102. 8. Piddock LVJ, Wise R. Mechanisms of resistance to quinolones and clinical perspectives. J Antimicrob Chemother 1989; 23: 475-83. 9. Munshi MH, Sack DA, Haider K, et al. Plasmid-mediated resistance to nalidixic acid in Shigella dysenteriae type 1. Lancet 1987; ii: 419-21. 10. Rogerie R, Ott D, Vandepitte J, et al. Comparison of norfloxacin and nalidixic acid for treatment of dysentery caused by Shigella dysenteriae in adults. J Antimicrob Chemother 1986; 29: 883-86. 11. Wang C, Sabbaj J, Corrado M, et al. World-wide clinical experience with norfloxacin: efficacy and safety. Scand J Infect Dis 1986; 48: (suppl) 81-89. 12. DuPont HL, Corrado ML, Sabbaj J. Use of norfloxacin in the treatment of acute diarrheal disease. Am J Med 1987; 82: S 79-83. 13. Ericsson CD, Johnson PC DuPont HL, et al. Ciprofloxacin or trimethoprim sulfamethoxazole as initial therapy for traveller’s diarrhea. Ann Intern Med 1987; 106: 216-20. 14. Pichler HET, Diridl G, Stickler K, Wolf D. Clinical efficacy of ciprofloxacin compared with placebo in bacterial diarrhea. Am J Med
1987; 82: 329-32. 15. Lolenkha S, Patanacharoen S. Clinical and microbiologic efficacy of norfloxacin for treatment of acute diarrhea. Rev Infect Dis 1988; 10: S 210-11. 16. Goodman LJ, Trenholme GM, Kaplan RL, et al. Empiric antimicrobial therapy of domestically acquired acute diarrhea in urban adults. Arch Intern Med 1990; 150: 541-46. 17. Piddock LVJ, Whale K, Wise R. Quinolone resistance in salmonella: clinical experience. Lancet 1990; 335: 1459. 18. Gorbach SL. Bacterial diarrhoea and its treatment. Lancet 1987; ii: 1378-82. 19. Damjanovic V, Willietts TH, Glynne Thomas D, et al. Eradication of salmonella by oral ciprofloxacin in food handlers. Lancet 1990; 335: 974. 20. Williams HMS, Richards J. Single-dose ciprofloxacin for shigellosis. Lancet 1990; 335: 1343-44. 21. Willocks LJ, Thompson C, Emmanuel FXS, et al. Hospital outbreak of Salmonella enteriditis infection treated with ciprofloxacin. Lancet 1990; 335: 1404-05.
REFLUX AND RESPIRATORY SYMPTOMS Much has been written about gastro-oesophageal reflux (GOR) and respiratory disorders since Kennedy’ first proposed an association almost 30 years ago. Numerous respiratory complaints have been attributed to acid reflux,2-4 but asthma has attracted most attention.5-10 Since reports with persuasive pathophysiological data in support of this
