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Fluoroquinolones Safe and Effective for Osteomyelitis: Presented at ECCMID

By Chris Berrie

BARCELONA, Spain -- April 22, 2008 -- Fluoroquinolones are as safe and effective as beta-lactams for the treatment of osteomyelitis, according a meta-analysis of randomised controlled trials (RCTs) presented here at the 18th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).

Osteomyelitis remains difficult to cure because the infected bone can become necrotic and avascular, and thus, systemic antibiotics cannot adequately penetrate to the infected site. In addition, the infections can show both Gram-positive (mainly Staphylococcus aureus) and Gram-negative (mainly Pseudomonas aeruginosa) pathogens.

Therefore, treatment options need to have broad-spectrum antimicrobial activity, although most can only be administered intravenously (IV). They also often need to be administered as combination regimens, leading to more toxicity and higher costs.

Coinvestigator Dimitrios Matthaiou, MD, Research Fellow, Alfa Institute of Biomedical Sciences, Athens, Greece, indicated in his presentation on April 19 that the fluoroquinolones would appear to satisfy the necessary criteria for use here. They have a broad antimicrobial spectrum, can be administered either IV or orally, and have good oral availability for bone and adjacent soft-tissue penetration.

Dr. Matthaiou and colleagues conducted a search and identified 7 RCTs. These showed comparators of ciprofloxacin (3 studies), ofloxacin (3 studies), and pefloxacin (1 study). These were administered either exclusively parenterally (5 studies) or IV and then orally (1 study); the administration route for 1 RCT was not clear. Fluoroquinolones were administered either exclusively orally (4 studies), or parenterally then orally (3 studies).

The researchers analysed benefits of fluoroquinolone versus beta-lactam therapy according to the Mantel-Haenszel fixed-effect model. Treatment success was defined as resolution of all signs and symptoms of active infection (7 RCTs, 194 patients). Bacteriological success was defined as absence of all causative organisms. Superinfections were defined as isolation of new pathogens from site of infected bone.

Treatment success showed an odds ratio (OR) of 0.99 (95% confidence interval [CI], 0.51-1.91; P = .97), and bacteriological success (6 RCTs; 201 isolates) had an OR of 0.88 (95% CI, 0.45-1.70; P = .71).

For superinfections (6 RCTs; 173 patients), treatment tended to be fluoroquinolones, with an OR of 1.75 (95% CI, 0.63-4.90; P = .28), and this drug class was also used for reappearance of the causative pathogen (5 RCTs; 153 patients), (OR, 1.23; 95% CI, 0.46-3.31; P = 0.68).

Adverse events were evaluated in 5 RCTs (170 patients) and showed a trend towards benefit for fluoroquinolones, with an OR of 0.47 (95% CI, 0.21-1.06; P = .07).

This analysis shows that fluoroquinolone use for treatment of patients with osteomyelitis is indeed as effective and safe as beta-lactam use. Therefore, Dr. Matthaiou stressed, the advantages of fluoroquinolones will lie mainly in their oral administration, with comparator beta-lactams generally administered IV.

He also indicated some limitations of this analysis, with the overall total numbers of patients remaining relatively small, making true differences between compared treatments difficult to detect. The studies were also generally conducted more than 15 years ago and yielded quality assessments with Jadad scores for study design/reporting quality of 2, indicating weak design/quality, he said.

However, these are all RCTs, and they indicate that fluoroquinolones are indeed useful oral alternatives for treatment of patients with osteomyelitis in an outpatient setting. "However, they should be used with caution and according to the resistance patterns of the pathogens in each setting to preserve their potency against increasingly resistant bacteria," he added.


[Presentation title: Fluoroquinolones Versus Beta-Lactam-Based Regimens for the Treatment of Osteomyelitis: A Meta-Analysis of Randomised Controlled Trials. Abstract O81]

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