Quinolones ========== þ Cost (for community-acquired pneumonia, all for 10 days) - Rexar (grepafloxacin) 600 mg daily $61.80 - Levaquin (levofloxacine) 500 mg daily $73.51 - Floxin (ofloxacin) 400 mg BID $87.46 - Zagam (sparfloxacin) 400 mg stat + 200 daily $73.58* *slightly better in vitro against PCN-resistant pneumococcus - Cipro (ciprofloxacin) 500/750 mg BID $72.47 þ Psych: - Known to cause psychosis, especially in the elderly [Sternbach H, State R, Harv Rev Psychiatry 1997;5:214] [Abouesh A et al. J Clin Psychopharmacol 2002;22:71] - but sulfa and cephalosporins and Flagyl can cause confusion, too [Sternbach H, State R, Harv Rev Psychiatry 1997;5:214] þ Hypoglycemia þ Fourth generation fluoroquinalones - Moxifloxacin + 400 mg daily + less likely to induce resistance + less likely to cause phototoxicity + fewer interactions - Gatafloxacin (Tequin) + 200 mg BID Oxazolidinones - Linezolid + covers atypicals, gram positves. + used for sick patients with VRE or other bad Gram + infection Daptomycin - Vanco derivative - shelved due to neurotoxicity, CPK elevations, renal excretion Synercid - for MRSA, VRE Trovafloxacin (Trovan) þ for children Does anyone have any experience in the use of quinolones in children? Although the official product labeling for these drugs does not sanction their use under the age of 18, my understanding is that human toxicity, unlike early animal studies, has not confirmed the occurence of cartilage abnormalities (1,2,3,4). On the advice of the head of our ID department we did give use it in a 6 year old a few months ago. H. Louzon MD (1) Hayem G, Carbon C A reappraisal of quinolone tolerability. The experience of their musculoskeletal adverse effects. Drug Saf 1995 Dec;13(6):338-42 The experience of the rheumatological adverse effects of fluoroquinolones should be helpful for both toxicologists and epidemiologists. In the case of fluoroquinolone-related arthropathy, the paediatric clinical experience seems to support the possible use of newer derivatives like ciprofloxacin in children who really need it. This therapeutic attitude is still contradictory to the labelling of fluoroquinolones. Inversely, there has been an important time-lag between the first reports of fluoroquinolone-related tendinopathies and the official recognition of this unusual toxic phenomenon. This delay, along with the widespread use of fluoroquinolones, makes it difficult to return to more reasonable prescribing guidelines for these very useful and effective anti-microbial compounds. The reasons why potentially serious adverse effects of fluoroquinolones were not anticipated before their commercialisation may be related to the lack of adequate in vitro and in vivo models, and the unexpectedness of the events. When it occurs, fluoroquinolone-induced arthropathy is most frequently benign, and heals without sequelae. The prognosis is not so favourable in the case of fluoroquinolone-related tendinopathy, which carries an important risk of immediate or secondary tendon rupture. Increasingly, fluoroquinolones are being prescribed for benign infections of the urinary or bronchopulmonary tracts. Sometimes, they are even used for antimicrobial prophylaxis before surgical or endoscopic procedures. We believe that for any prescription, the risk/benefit ratio of the fluoroquinolones should be carefully considered, since better tolerated, less expensive drugs can usually be prescribed. Clear information dedicated both to physicians and patients regarding the cautions for use and possible adverse effects of fluoroquinolones would help reduce the risk and severity of adverse reactions. This is especially important for phototoxicity, tendinopathy and cardiovascular adverse effects. As underlined by Ball and Tillotson in this issue, the future clinical use of the fluoroquinolones will be determined by the balance between the antibacterial efficacy and adverse effects of these agents. The adverse reactions affecting the musculoskeletal system provide a good example of this dilemma. Given the absence of an adequate model of tendinopathy and the poor predictivity of animal manifestations in arthropathy and cartilage lesions in humans, careful monitoring of patients during phase II and III trials and, more importantly, long term pharmacovigilance during the postmarketing period, are still strongly warranted. (2) Pradhan KM, Arora NK, Jena A, Susheela AK, Bhan MK Safety of ciprofloxacin therapy in children: magnetic resonance images, body fluid levels of fluoride and linear growth. Acta Paediatr 1995 May;84(5):555-60 We evaluated the safety of ciprofloxacin administered in a dose of 15-25 mg/kg for 9-16 days, in a case series of 58 children who were between 8 months and 13 years of age. No arthropathy was observed during therapy and follow-up. Blinded evaluation of 22 pairs of nuclear magnetic resonance scans obtained before and between day 10 and 15 of therapy did not reveal any cartilage damage. After the first dose of ciprofloxacin (10 mg/kg), serum fluoride levels increased at 12 h in 15 of 19 (79%) patients; 24-h urinary fluoride excretion was higher on day 7 compared with basal values in 16 of 18 (88.9%) patients. Height z scores of 53 patients at a mean of 22.5 months of follow-up were not significantly different from basal scores (p = 0.12). In conclusion, ciprofloxacin may be recommended for use in children for short duration when effective alternative antibacterials are unavailable. However, there is a need for further studies to evaluate the tissue accumulation of fluoride and its potential to cause toxic effects. (3) Schaad UB Use of the new quinolones in pediatrics. Isr J Med Sci 1994 May-Jun;30(5-6):463-8 For many years quinolone-induced cartilage toxicity observed in experiments with some skeletally immature animals represented indisputable contraindication for the use of these promising antimicrobials in prepubertal patients. Our clinical, magnetic resonance imaging and histopathological monitoring of ciprofloxacin use, together with the published experiences of other groups, suggest that the quinolone antibiotics do not cause arthropathy in humans. Conditions that potentially qualify for quinolone use (especially ciprofloxacin) in children include oral antipseudomonal (or antistaphylococcal) therapy for pulmonary exacerbation in cystic fibrosis, and for complicated urinary tract, skeletal, aural and shunt infections. In addition to these rare indications, there is an urgent need in developing countries for availability of the new quinolones for treating children with endemic and epidemic shigellosis and invasive salmonellosis. At present these compounds are not approved for pediatric patients; therefore each such treatment must be part of a controlled study or respect the compassionate use regularities. (4) Danisovicova A, Brezina M, Belan S, Kayserova H, Kaiserova E, Hruskovic I, Orosova K, Dluholucky S, Galova K, Matheova E, et al Magnetic resonance imaging in children receiving quinolones: no evidence of quinolone-induced arthropathy. A multicenter survey. Chemotherapy 1994 May-Jun;40(3):209-14 Twenty-nine children with cystic fibrosis (CF) were investigated for quinolone-induced arthropathy. Magnetic resonance imaging (MRI) was performed in 14/14 children treated with ofloxacin or ciprofloxacin and in 10/15 of those never treated with quinolones. The frequency of pathologic MRI findings, concerning cartilage thickness, careful analysis of the cartilage structure, presence of edema, cartilage-bone borderline and the presence of fluid in joints did not show any difference between both groups. Thus the presence of quinolone-induced arthrotoxicity cannot be confirmed in this study.