Lesson of the Week: Dangers of oral fluoroquinolone treatment in community acquired upper respiratory tract infectionsBMJ 1994; 308 doi: https://doi.org/10.1136/bmj.308.6922.191 (Published 15 January 1994) Cite this as: BMJ 1994;308:191
- J R Korner,
- S D Reeves,
- P A MacGowan
- Department of Medical Microbiology and Regional Antimicrobial Reference Laboratory, Southmead Health Services NHS Trust, Westbury- on-Trym, Bristol BS10 5NB
- Correspondence to: Dr Korner.
- Accepted 13 July 1993
Respiratory tract infections are among the commonest presenting to general practitioners. Upper respiratory tract infections of bacterial origin, such as acute otitis media and sinusitis, are commonly caused by Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, and Moraxella catarrhalis. Lower respiratory tract infections, such as pneumonia, are most commonly caused by Streptococcus pneumoniae2,3 followed by Mycoplasma pneumoniae.4 The antimicrobial agents most often used for empirical treatment of these infections are amoxycillin, co-amoxiclav, and erythromycin. We have noticed that fluoroquinolones such as ciprofloxacin and ofloxacin are increasingly being used to treat community acquired upper respiratory tract infection even though they have poor activity against S pneumoniae. We report here two cases of life threatening systemic pneumococcal infection originating in the upper respiratory tract in which a fluoroquinolone was prescribed unsuccessfully as first line empirical antibiotic treatment.
A previously fit 28 year old woman was admitted with acute onset of severe headache and subsequent confusion and agitation. Two weeks earlier she had experienced a flu-like illness, with migraine-like headache, worsening cough, and large amounts of pus discharging from her nose. In the early morning before admission she had woken up with severe frontal headache worsening when leaning forward. She was seen urgently by her general practitioner, who found her blood pressure normal, a pulse rate of 90 beats/min, and a temperature of 39.5°C. She was given 100 mg pethidine intramuscularly for pain relief and 500 mg ciprofloxacin by mouth. Four hours later her general practitioner referred her to hospital.
A computed tomographic scan of her head showed bilateral opaque maxillary and ethmoidal sinuses but no sign of raised intracranial pressure or intracranial abnormalities. A turbid cerebrospinal fluid on lumbar puncture showed a white cell count of 13.5x104/l, 99% of which were polymorphonuclear white cells, and an erythrocyte count of 80x10(SUP 4)/l. The Gram film showed Gram positive cocci suggestive of pneumococci. As a penetrating sinus abscess could not be excluded treatment was started with 3 g cefotaxime every six hours and 500 mg metronidazole every eight hours. The next day S pneumoniae serotype 6, sensitive to penicillin, was isolated from the cerebrospinal fluid, blood cultures, and the pus from her nose. Her treatment was changed to 1.8 g benzylpenicillin three hourly intravenously. Serum concentrations of penicillin were maintained below toxic concentrations. Over the 10 day course she recovered slowly but steadily.
A 67 year old man was admitted with a three day history of right sided muscular weakness, sore throat, and severe dehydration due to worsening dysphagia. His history was unremarkable apart from hypertension and shortness of breath on exertion. A week before admission an upper respiratory tract infection had been diagnosed and treated with oral ofloxacin and linctus by his general practitioner. On admission he had a temperature of 38.5°C and painful, swollen, and hot right elbow and ankle joints as well as swollen metacarpophalangeal joints of the right hand.
While being admitted he developed severe stridor and an emergency intubation had to be performed. He developed septic shock and was admitted to the intensive care unit, where an ankle aspirate was taken. A Gram film showed streptococci and intravenous penicillin and netilmicin was started. A laryngoscopy performed in the intensive care unit showed a large solid laryngeal cyst, though no specimen was taken for culture. Next day S pneumoniae serotype 9, sensitive to penicillin and resistant to ofloxacin, was isolated from blood cultures and from the ankle aspirate. Subsequently an IgG myeloma and diabetes mellitus were diagnosed. The patient recovered slowly from this episode of septic polyarthritis complicated by acute renal failure and was discharged from intensive care after four weeks.
The oral fluoroqumolones currently available in the United kingdom, ofloxacin and ciprofloxacin, show excellent activity against Gram negative organisms, but their activity against Gram positive organisms, in particular streptococci and pneumococci, is limited. The minimum inhibitory concentrations of ofloxacin against S pneumoniae range from 1 to 4 mg/l and of ciprofloxacin from 0.5 to 4 mg/l, concentrations which are only marginally exceeded in bronchial secretions.5 In addition, there is in vivo and in vitro selection of ciprofloxacin resistant mutants of previously sensitive pneumococcal isolates.6,7 According to their datasheets both antibiotics are licensed for treating respiratory tract infections, but the datasheet for ciprofloxacin does not recommend it in S pneumoniae infection8; that for ofloxacin states that in vitro activity against S pneumoniae is variable.9
Though our second patient presented with symptoms of an upper respiratory tract infection, his malignant haematological disorder probably made him more susceptible to invasive pneumococcal disease. Even though the myeloma was not suspected, the use of ofloxacin as initial treatment is questionable. The pneumococcal scrotype isolated is not especially pathogenic, nor does it have an uncommon sensitivity pattern which might explain the failure of treatment.10,11 As a non-bacterial infective agent was the more likely cause of his initial upper respiratory tract infection, ofloxacin might have exerted selective pressure on the upper respiratory tract flora, leading to the emergence of S pneumoniae as a secondary pathogen. That ciprofloxacin was the initial choice of antibiotic in our first patient is worrying since a likely cause of her purulent nasal discharge was sinusitis, which is commonly caused by pneumococci.
Early clinical and experimental studies reported that ofloxacin was successful in treating otitis media and acute sinustitis caused by S pneumonise and Staphylococcus aureus,12,13 but only a few patients were investigated and neither diagnostic methods nor evaluation criteria have been reported in full in English. Life threatening and fatal pneumococcal infections such as meningitis have subsequently been reported in patients treated with ciprofloxacin for respiratory tract infection or otitis media.14,15 The point these two cases reinforce is that neither ofloxacin nor ciprofloxacin is indicated for initial treatment of community acquired upper respiratory tract infection where S pneumoniae is likely to be a pathogen. The antibiotic of choice should be fully active against S pneumoniae as well as the other likely bacterial pathogens.