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SPINE Volume 33, Number 10, pp E297–E304

©2008, Lippincott Williams & Wilkins

Fluoroquinolones Versus ␤-Lactam Based Regimens for
the Treatment of Osteomyelitis
A Meta-Analysis of Randomized Controlled Trials
Eirinaios M. Karamanis, MD,* Dimitrios K. Matthaiou, MD,* Lampros I. Moraitis,†
and Matthew E. Falagas, MD, MSc, DSc*‡§

Study Design. A meta-analysis of randomized control
trials.
Objective. To compare fluoroquinolones to ␤-lactams
for the treatment of osteomyelitis.
Summary of Background Data. Treatment of osteomyelitis remains a real challenge in medicine necessitating
the use of broad-spectrum antibiotics, because of the
variety of the pathogens causing the infection and the fact
that the infected bone may become necrotic and avascular, preventing systemic antibiotics from adequately penetrating to the infection site.
Methods. A literature search was performed by 2 reviewers independently (PubMed database and the Cochrane Central Register of Controlled Trials).
Results. We identified 7 studies eligible for inclusion in
our meta-analysis; ciprofloxacin, ofloxacin, and pefloxacin were used in 3, 3, and 1 study, respectively, while
various ␤-lactams (mainly in the intravenous form) were
used as comparators. There was no difference in treatment success for osteomyelitis between fluoroquinolones and ␤-lactams [194 patients, fixed effect model (FEM),
odds ratio (OR) ⫽ 0.99, 95% confidence interval (CI) 0.51–
1.91], bacteriological success (201 isolates, FEM, OR ⫽ 0.88,
95% CI ⫽ 0.45–1.70), superinfections (173 patients, FEM,
OR ⫽ 1.75, 95% CI ⫽ 0.63– 4.90), relapses (153 patients, FEM,
OR ⫽ 1.23, 95% CI ⫽ 0.46 –3.31), or adverse events (170
patients, FEM, OR ⫽ 0.47, 95% CI ⫽ 0.21–1.06).
Conclusion. Fluoroquinolones are as effective as ␤-lactams for the treatment of osteomyelitis and can be considered as a useful alternative in the physician’s armamentarium. The value of fluoroquinolones for the treatment of
osteomyelitis lies in the fact that they can be administered in
an outpatient setting. However, they should be used with
caution, so as to preserve their activity against increasingly
resistant bacteria.
Key words: ciprofloxacin, ofloxacin, pefloxacin, imipenem, diabetic foot. Spine 2008;33:E297–E304

Osteomyelitis remains a difficult to cure clinical entity,
having a devastating impact on patients’ quality of life
and sense of well being, despite the advent of many new
From the *Alfa Institute of Biomedical Sciences (AIBS), Athens,
Greece; †National Technological University of Athens, Greece; ‡Department of Medicine, Henry Dunant Hospital, Athens, Greece; §Department of Medicine, Tufts University School of Medicine, Boston,
MA.
Acknowledgment date: November 20, 2007. Revision date: December
12, 2007. Acceptance date: December 18, 2007.
The manuscript submitted does not contain information about medical
device(s)/drug(s).
No funds were received in support of this work. No benefits in any
form have been or will be received from a commercial party related
directly or indirectly to the subject of this manuscript.
Address correspondence and reprint requests to Matthew ⌭. Falagas,
MD, MSc, DSc, Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Greece; E-mail: m.falagas@aibs.gr

antibiotics. The cause for the difficulty in the treatment of
osteomyelitis is that infected bone may become necrotic
and avascular and thus systemic antibiotics cannot adequately penetrate to the infection site. Gram-positive
bacteria, mainly Staphylococcus aureus and streptococci, as well as gram-negative pathogens, mainly
Pseudomonas aeruginosa and Enterobacteriaceae are
commonly responsible for osteomyelitis.1– 4 Thus, the
use of broad-spectrum antibiotics is warranted for the
treatment of osteomyelitis.
Until the advent of fluoroquinolones, recommended
regimens for the treatment of osteomyelitis included
cephalosporins, alone or in combination with aminoglycosides, carbapenems, antipseudomonal penicillins
along with ␤-lactamase inhibitors, vancomycin, and trimethoprim/sulfonamide combinations. The above
agents have a broad spectrum of antimicrobial activity
coupled with sufficient penetration in bone tissue, but
many of them are administered only intravenously, a fact
that renders them inconvenient for the long duration
treatment of osteomyelitis. They are also usually administered in combination regimens, leading to higher toxicity and cost of therapy.
Fluoroquinolones may alternatively be used for the
treatment of osteomyelitis, because they have a broad
antimicrobial spectrum covering a wide range of grampositive and gram-negative bacteria. In addition, they
may be administered either intravenously or orally,
which is a more comfortable and less annoying route for
patients. Furthermore, fluoroquinolones have good oral
bioavailability and satisfactory penetration in bone and
adjacent soft tissue.5,6
For all the aforementioned reasons, fluoroquinolones
seem an appealing option for the treatment of bone and
joint infections and especially for the treatment of osteomyelitis. To examine the above hypothesis, we conducted a
meta-analysis of randomized control trials comparing fluoroquinolones to ␤-lactams and other conventional agents
for treatment of osteomyelitis.
Methods
Data Sources
Two reviewers (D.K.M. and E.M.K.) independently performed
the literature search. The studies for our meta-analysis were
retrieved from a search of the PubMed database and the Cochrane Central Register of Controlled Trials. Search terms included the terms “osteomyelitis,” “quinolones,” “␤-lactams,”
and the individual names of fluoroquinolones. Any disagreement between the 2 reviewers regarding the evaluability of a
E297

Pooled odds ratios and 95% confidence intervals (CIs) for all primary and secondary outcomes were calculated by using both the Mantel-Haenszel fixed-effect model 9 and the DerSimonian-Laird random-effects model. the maximum score for a study was 5.13–16 In one RCT. From those. and evaluates the appropriateness of randomization and blinding. we present the characteristics (patient population. duration of treatment. We identified 287 potentially relevant studies that included patients with osteomyelitis. Study Selection Criteria The identified relevant studies were further evaluated. bacteriological success. . reviews. a score higher than 2 points denotes a good quality RCT according to this methodology. For studies not focusing exclusively on patients with osteomyelitis. and (d) computed tomography or magnetic resonance imaging. Furthermore.M.15 Fluoroquinolones were administered exclusively orally in 4 out of 7 RCTs. the location and extend of focus of osteomyelitis.12. and follow-up) of the RCTs included in our meta-analysis. performed.E298 Spine • Volume 33 • Number 10 • 2008 study was resolved by consensus in meetings that involved all authors. The remaining 7 studies met the inclusion criteria and were evaluated further. the adjunctive treatments used (if any).7. the type of therapeutic regimens used.16. The primary outcome of our meta-analysis was defined as treatment success of each regimen.12 whereas in one RCT.13. who were treated with fluoroquinolones or other conventional agents. whereas the latter 2 criteria could be awarded the values of ⫺1 (inappropriate). otherwise.17 With the exception of the study by Gomis et al12 and by definition for the study by Lipsky et al.11–13 and pefloxacin in 1 study. The data extracted from each study included the author names and year of publication. the population of interest. Superinfection was defined as isolation of new pathogens from the site of the infected bone during the course of therapy. Relapse was defined as reappearance of the causative pathogen during follow-up..1⬘ software (Insightful Corp. Bias of small studies was assessed by the funnel plot method using the Egger test. the route of administration is not clear. the duration of therapy and of the follow-up. the bacteriological success. and information on withdrawals from the study.M. exclusively or as a subset of the whole study population. and E. Definition of Outcomes Patients were considered to have osteomyelitis. case series. fluoroquinolones were administered parenterally and subsequently orally. a P value less than 0. WA). after prior clinical signs or microbiological data of eradication.K.11. if present. which examines whether there is randomization. when the diagnosis was confirmed by bone biopsy or alternatively was established by appropriate findings in at least 2 of the following diagnostic methods: (a) clinical examination. Cure was defined as resolution of all signs and symptoms of active infection at the end of follow-up period. and patients with adverse events. no data regarding surgical procedures undertaken after the enrollment of patients in the trials were reported. which were the newer ones. animal or laboratory studies. and number of patients experiencing adverse events due to the administered regimens. which were the older ones. the number of patients. superinfections. (b) conventional radiography. superinfections.10 For all analyses. or retrospective studies. Data Extraction Two reviewers (D. (c) bone scanning.17 whereas in the other 3 RCTs. and (3) if it included more than 10 patients in each treatment arm. Seattle. A study was considered eligible for inclusion in our meta-analysis if: (1) it was a randomized controlled trial comparing fluoroquinolones with other conventional agents for the treatment of patients with osteomyelitis.) independently extracted and tabulated the data from the selected studies. Patients in the first treatment arm of all RCTS received fluoroquinolones. Also. 0 (no data). results from the random effects model are presented.K.17 ofloxacin in 3 studies.14. blinding.11. Results Study Selection Process In Figure 1. the superinfections and/or the patients with adverse events. Bacteriological success was defined as absence of all causative organisms from the culture at the end of follow-up. the relapses.10 was defined to denote the presence of statistically significant heterogeneity between studies.11–17 Study Characteristics In Table 1.14.16. imaging studies. relapses. results obtained with the fixed-effect model (FEM) are presented if there was no heterogeneity between studies. 220 studies were excluded because they were case reports. ␤-lactams were administered intravenously and subsequently orally. Fifty-six studies were further excluded because they constituted noncomparative studies. The reviewers calculated the Jadad score of each study independently. In 5 out of 7 RCTs. as well as treatment success. The heterogeneity between studies was assessed by using the ␹2-test.8 One point was awarded for the presence of each of the former 3 criteria. The reported outcomes of the analyzed studies were weighted by the inverse of their variance with the fixed-effect model. The fluoroquinolones used were ciprofloxacin in 3 studies. Validity Assessment A review of the quality of each RCT included in our metaanalysis was performed by using the Jadad score.15 Patients in the second treatment arm received ␤-lactams.12 no specific data were reported regarding the location and extend of focus of osteomyelitis. (2) it reported data regarding the clinical success of the treatment. Statistical Analysis Statistical analyses were performed using the ‘S-Plus 6. The secondary outcomes of our meta-analysis included bacteriological success. and ⫹1 (appropriate). relapses. administered drugs. we extracted the data which were reported particularly for the subset of patients with such infections. 3 studies were excluded because they were not randomized controlled trials and another study was excluded because it included a small number of patients. ␤-lactams were administered exclusively via the parenteric route. Thus. we present a flow diagram depicting the various steps of the study selection process.

75. we present data regarding the primary and secondary outcomes.91. OR ⫽ 1. Data about treatment success were provided in all 7 RCTs included in our meta-analysis.23. 95% CI ⫽ 0. There was no difference in relapses between fluoroquinolones and ␤-lactams (153 patients.99.Fluoroquinolones for Osteomyelitis • Karamanis et al E299 Figure 1.13–17 The follow-up period for the evaluation of relapses ranged from 6 to 18 months.31.71). P ⫽ 0. 95% CI ⫽ 0. The odds ratios for treatment success in the individual RCTs. FEM. Relapses Data about relapses were reported in 5 out of 7 RCTs. odds ratio (OR) ⫽ 0.11. Flow diagram of the study selection procedure. are presented in Figure 2(B).90. FEM. OR ⫽ 0. there was no statistically significant difference in the superinfections between fluoroquinolones and ␤-lactams (173 patients. are presented in Figure 3(A).13–17 There was no difference in bacteriological success between the 2 compared treatments (201 isolates. as well as the pooled odds ratio.51–1. as well as the pooled odds ratio. P ⫽ 0. The odds ratios for relapses in the individual RCTs.46 –3.28). 95% CI ⫽ 0. FEM. as well as the pooled odds ratio. P ⫽ 0.97]. .63– 4.11. Treatment Success In Table 2.11–17 There was no difference in treatment success between fluoroquinolones and ␤-lactams [194 patients. OR ⫽ 1.13–17 Although superinfections were more frequent in patients receiving fluoroquinolones. are presented graphically in Figure 2(A). Superinfections Data about superinfections were reported in 6 out of 7 RCTs. Bacteriologic Success Data about bacteriological success of fluoroquinolones versus ␤-lactams were provided in 6 out of 7 RCTs. FEM.68). The odds ratios for bacteriologic success in the individual RCTs. as well as the pooled odds ratio. P ⫽ 0.88. are presented in Figure 3(B). 95% CI ⫽ 0.45–1.70. The odds ratios for superinfections in the individual RCTs.

The odds ratios for patients with adverse events in the individual RCTs. superinfections. FEM. Before enrollment all infections had been surgically debrided and all foreign metallic material was removed Patients with chronic osteomyelitis in exacerbation Broad spectrum cephalosporin i.47.16 –17 There was no difference in the number of patients experiencing adverse events between fluoroquinolones and ␤-lactams. of patients who received adjunctive antibiotics For the cefazolin group. No data reported about the no. Discussion The main finding of our meta-analysis is that fluoroquinolones were as effective as ␤-lactams regarding the primary outcome of treatment success for patients with osteomyelitis. q12h Giamarellou et al. it should be noted that in 4 of the 7 included studies fluoroquinolones were administered . trimethoprim/sulfamethoxazole. vancomycin. q8h when appropriate Open-label RCT Patients with chronic biopsyconfirmed osteomyelitis. i.13–14. OM. q8h to q12h. imipenem. when appropriate Ampicillin 1–2 g/sulbactam 0.21–1.v.v. P ⫽ 0. OR ⫽ 0. 199014 Open-label RCT Ciprofloxacin 750 mg p.v. not applicable.o. Neutropenic patients and patients with uncontrolled diabetes were excluded Lipsky et al. 198916 Open-label RCT Patients with acute and chronic osteomyelitis Greenberg et al. 199712 Open-label multicenter RCT Gentry and RodriguezGomez. relapses. bacteriological success. every 6 h. q12h Cefazoline 1 g i. q8h Clindamycin in the first group when there was a suspicion or isolation of anaerobic pathogens. q12h (if not possible it was administered i.v. †␤-Lactams. or p. are presented in Figure 3(C). q8h or ceftazidime 2 g i.11.o.o.E300 Spine • Volume 33 • Number 10 • 2008 Table 1.v. namely. q12h.07). 4 out of 14 patients received cloxacillin sodium in this group NA Snydman et al.o. (usually ceftazidime) or nafcillin-aminoglycoside combination (usually amikacin) Ceftazidime 2g i. 198717 Open-label RCT Patients with chronic osteomyelitis Pefloxacin 400 mg i. followed by p.v. Patients with evidence of OM were not to be enrolled unless all of the infected bone was to be removed soon after enrollment Ofloxacin 400 mg i.v. Ciprofloxacin 750 mg p. every 12 h.m. 199911 Open-label RCT Patients with chronic osteomyelitis. q12h changed to p. and patients with adverse events. as well as i. 199113 Fluoroquinolone Regimen Other Regimen Adjunctive Treatments Ofloxacin 400 mg p. No data regarding the no. Also. p. NA. intravenously.) Imipenem/cilastatin 500 mg i. q8h. q8h or 1g i. 198915 Open-label RCT Patients with acute or chronic biopsy-confirmed osteomyelitis. *n 7 out of 8 cases pefloxacin was given for 180 d. Patients With Adverse Events Data about patients with adverse events were provided in 5 out of 7 RCTs. q12h Ciprofloxacin 750 mg p. of patients who received clindamycin Metronidazole to ofloxacin and gentamicin. q6h Patients with osteomyelitis due to diabetic foot infections.v.o. osteomyelitis. aminoglycosides. q6h changed to amoxicillin 500 mg/ clavulanic 125 mg p. trimethoprimsulfamethoxazole or another agent to aminopenicillin for better gram-negative coverage. cloxacillin sodium was administered following cefazoline therapy for chronic suppression of Staphylococcus aureus OM in elderly subjects with histories of relapses. q12h (q8h for Pseudomonas aeruginosa infections) Gentry and Rodriguez. clindamycin. per os.o. q12h NA Alternative parenteral antimicrobial therapy with ␤-lactams NA Another appropriate antimicrobial therapy† NA RCT indicates randomized controlled trial.o.5–1 g i.v. Patients with prosthetic material were not enrolled Ofloxacin 400 mg p. Main Characteristics of the Included Randomized Controlled Trials Author (Year) Study Design Population Gomis et al. 95% CI ⫽ 0.o. no difference was found between the 2 treatments in the analyses of secondary outcomes.06. q6h. as well as the pooled odds ratio. although there was a trend in favor of treatment with quinolones (170 patients.o. However. every 8 h.o.v.v.

6 Also. Continued Enrolled Patients Intention to Treat Patients 32 21 108 21 NA 42 33 [2/19 (11%) patients and 1/14 (7%) had diabetes in the 2 arms respectively] NA 67 59 [1/31 (3%) patients and 4/28 (14%) had diabetes in the 2 arms respectively] NA 103 Location and Extend of Focus of OM First group: 8 cases with contiguous OM. 3 postsurgical. fluoroquinolones appear as a valid alternative for initiation or continuation of the long-term treatment required for osteomyelitis allowing better compliance. 2 OM of the foot in patients with DM. performed by Stengel et al. proportion with prostheses. 2 postsurgical. 30 d 18 mo 2 56 d vs. meaning that fluoroquinolones tend to concentrate in tissues. 4 post-traumatic. there has been only one relevant meta-analysis. Fluoroquinolones have high oral bioavailability ranging from 63% to 69% for ciprofloxacin to more than 95% for ofloxacin and pefloxacin in healthy subjects. One immunosuppressed patient (renal transplantation) in the comparator group] 56 d vs. 1 associated with prosthetic device Lower extremities The 2 groups were comparable with respect to proportion of patients with chronic OM.v. and location of OM NA Follow-up Period Quality Assessment 30–45 d 6 mo 2 9 d vs. 44 d NA 2 30 30 [One patient with metal appliance at site of infection in the ciprofloxacin group. the results were similar to the ones obtained in our meta-analysis. despite the fact that Mean Duration of Therapy the meta-analysis by Stengel et al included studies with a broader set of infections and administered antimicrobials and the primary outcome included patients who were either cured or improved at the end of treatment.18 in which several types of antibiotic therapies were examined for the treatment of both bone and joint infections.Fluoroquinolones for Osteomyelitis • Karamanis et al E301 Table 1. To our knowledge. 7 d i. superior tissue penetration of fluoroquinolones compared to other agents is retained . and 12 d vs. 13 d p. 44 d Up to 13 mo 1 orally while the comparator ␤-lactam agents were administered intravenously. 47 d 12 mo 2 15 4–6 mo* vs.o. The volume of distribution of fluoroquinolones is greater than total body water. In the subanalysis of fluoroquinolones versus nonfluoroquinolone control regimens. NA 2 54 d vs. Taking under consideration the fact that fluoroquinolones exhibit high bioavailability when administered orally. 6–8 wk 12 mo 3 29 21 72 d vs. 2 OM of the foot in patients with DM Second group: 6 cases with contiguous OM. Concentrations in bone were 30% to 80% of serum concentrations for ciprofloxacin and ofloxacin. 4 post-traumatic.

Figure 2.9) 2/28 (7. 199712 Gentry and RodriguezGomez. 199113 Gentry and Rodriguez.1) 6/31 (19.4) 7/11 (63.4) 5/28 (17.E302 Spine • Volume 33 • Number 10 • 2008 Table 2.5) 0/10 (0) 0/14 (0) 1/7 (14. Diamond ⫽ pooled odds ratio for all RCTs.3) 1/10 (10) NA 1/14 (7. NA indicates not available.6) 9/11 (81.4) 22/28 (78. Primary and Secondary Outcomes of the Analyzed RCTs Author (Year) Gomis et al.5) 14/19 (73.3) 7/8 (87.7) 7/10 (70) 1/4 (25) 12/14 (85.1) 0/8 (0) 3/10 (30) 1/14 (7. for studies comparing quinolones with ␤-lactams for the treatment of osteomyelitis. 198915 Snydman et al.1) 0/7 (0) 0/11 (0) 0/11 (0) 1/8 (12.1) NA NA 3/19 (15.3) NA 5/11 (45.8) NA NA 1/14 (7. Odds ratios of treatment success. 198916 Greenberg et al. the size of each square denotes the proportion of information given by each trial.3) 0/11 (0) 0/11 (0) NA 3/10 (30) 2/14 (14.5) 7/10 (70) 8/14 (57.2) 4/28 (14.6) 8/11 (72.7) 7/11 (63.8) . (B) bacteriological success (Vertical line ⫽ “no difference” point between the 2 regimens.5) 34/40 (85) 4/31 (12. (A) treatment success.7) 7/8 (87.9) 1/31 (3. 199014 Giamarellou et al.1) 6/16 (37. Horizontal lines ⫽ 95% CI).4) Values inside parentheses indicate percentages.5) 4/11 (36. 6/7 (85.5) 7/10 (70) 7/14 (50) 5/7 (71. 199911 Lipsky et al. and bacteriological success. Square ⫽ odds ratio. 198717 Treatment Success Bacteriological Success Superinfections Relapses Patients With Adverse Events 10/11 (90.8) 3/16 (18.6) 33/40 (82.7) 10/10 (100) NA 12/20 (60) 8/10 (80) NA 13/20 (65) 0/10 (0) NA 1/19 (5.6) 24/31 (77.1) 0/16 (0) NA 7/19 (36.8) NA 4/14 (28.

such as it is frequently encountered in sites of infection. trends of susceptibility of the pathogens to the examined agents may have changed considerably. Since then. Square ⫽ odds ratio.Fluoroquinolones for Osteomyelitis • Karamanis et al E303 Figure 3. which equals to the cut-off point for considering them as good quality RCTs. Second. but resistance to these agents has greatly increased in parallel with the rise in the prevalence of methicillin-resistant Staphylococcus aureus. Nevertheless. that fluoroquinolones are one of the few oral agents available for satisfactory coverage of the gram-negative pathogens that are frequently a cause of osteomyelitis. diabetic microangiopathy could further hamper fluoroquinolone penetration in the inflamed tissues. Horizontal lines ⫽ 95% CI). Nevertheless. host immu- . even in environments with low pH. in whom the peak serum concentrations rise accordingly. the size of each square denotes the proportion of information given by each trial. the quality assessment of the included studies yielded a score of 2. as well as the adequacy of the host inflammatory response. for empirical therapy. as the findings of our study show. Diamond ⫽ pooled odds ratio for all RCTs.19 However. fluoroquinolones initially exhibited substantial antistaphylococcal activity. Also. since osteomyelitis frequently coexists with diabetes mellitus. (Vertical line ⫽ “no difference” point between the 2 regimens. in our meta-analysis. There are certain limitations though that should be taken under consideration in our meta-analysis. and (C) patients with adverse events for studies comparing quinolones with ␤-lactams for the treatment of osteomyelitis. so it is arguable if the results of these studies could be applied in current clinical practice. First. Third.6 The aforementioned properties of fluoroquinolones could be considered as potential advantages over other agents. Moreover. most of them in a time span of 5 years between 1987 and 1991. fluoroquinolones should be better used in combination with an agent with sufficient activity against gram-positive pathogens. the included studies were conducted more than 15 years ago. So. (B) relapses. there was no difference in efficacy between fluoroquinolones and ␤-lactams for the treatment of osteomyelitis. It should be mentioned though. Odds ratios of (A) superinfections. caution is advised in the elderly or in individuals with renal failure or liver disease. which are expected to result in increased efficacy in clinical practice. active osteomyelitis lesions are surrounded by necrotic tissues and debris and have poor vascular supply. It should be also emphasized that factors such as acuity of osteomyelitis. the total number of patients included in our metaanalysis is rather small to allow for true differences between compared treatments to be shown. This finding may be appointed to the inherent characteristics of the osteomyelitis pathophysiology. without the cost of inferior treatment outcomes nor an increased rate of adverse events. Specifically. thus preventing adequate distribution of the antimicrobial drugs in the site. the value of fluoroquinolones for the treatment of osteomyelitis lies in the option that they offer for treatment in an outpatient setting.

Antimicrob Agents Chemother 1991. Randomized comparative trial of ciprofloxacin for treatment of patients with osteomyelitis.282:198 –206. Swartz MN. 3. 12. ● There was no difference in treatment success. Waldvogel FA. N Engl J Med 1970. et al. 11. Sanchez B. Osteomyelitis: a review of clinical features. Mantel N. Landon GC. Am J Med 1987. 4. Waldvogel FA. Osteomyelitis: a review of clinical features. therapeutic considerations and unusual aspects. Gomis M. Giamarellou H. and thus could be considered as a useful alternative in the physician’s armamentarium. 5. Osteomyelitis: a review of clinical features. Haenszel W. Marsh PK. Randomized trial of ciprofloxacin compared with other antimicrobial therapy in the treatment of osteomyelitis. References 1. Osteomyelitis associated with vascular insufficiency. Khan KS. N Engl J Med 1970.2:378 – 424. However. Bauwens K. Fluoroquinolone antimicrobial agents. 8. Sehouli J. J Natl Cancer Inst 1959. Jadad AR. Overview of osteomyelitis. The importance of quality of primary studies in producing unbiased systematic reviews.11:S1271–S1272. 14. Statistical aspects of the analysis of data from retrospective studies of disease.33:1362–7. 3.7:177– 88. 7. Clin Infect Dis 1997. In conclusion. Antimicrob Agents Chemother 1990.12:195–208. With the exception of acuity of infection.82:266 –9.E304 Spine • Volume 33 • Number 10 • 2008 nocompetency. Perdikaris G. Arch Intern Med 1996. Greenberg RN.87:23S–27S. the comparative outcomes should not have been influenced by the presence of these factors. Waldvogel FA. 2. Hooper DC. Daya S. Oral ofloxacin versus parenteral imipenem-cilastatin in the treatment of osteomyelitis. DerSimonian R. et al. Gentry LO.34:40 –3.156:661– 6. Barberan J. Tice AD. relapses. Medoff G. Galanakis N. Key Points ● A literature search was performed to identify randomized control trials comparing fluoroquinolones to ␤-lactams for the treatment of osteomyelitis. Moher D. Oral ciprofloxacin compared with parenteral antibiotics in the treatment of osteomyelitis.35:538 – 41. 18. Orthop Rev 1987. et al. Swartz MN.12:244 –9. Barza M. so as to preserve their potency against increasingly resistant bacteria. Current issues and future directions.16:255– 8. Baker PD.22:719 – 48. Rodriguez GG. reported data regarding these factors were scarce in the included studies. Antimicrob Agents Chemother 1989. However. 6. Am J Med 1989. Clin Microbiol Rev 1989. Jadad A. et al. Lancet Infect Dis 2001. therapeutic considerations and unusual aspects. 19. Int J Technol Assess Health Care 1996. Laird N. Thus. Pefloxacin versus ceftazidime in the treatment of a variety of gram-negative-bacterial infections. Antibiotic therapy for diabetic foot infections: comparison of two parenteral-to-oral regimens. Rev Infect Dis 1989. Mazza JA. 1:175– 88. 16. Gentry LO. adjunctive treatment and location and extend of focus of osteomyelitis may considerably influence the outcome of osteomyelitis. Medoff G. Swartz MN. Medoff G. Systematic review and meta-analysis of antibiotic therapy for bone and joint infections. especially for the oral treatment of osteomyelitis in an outpatient setting. Rodriguez-Gomez G. superinfections. Snydman DR. Ofloxacin versus parenteral therapy for chronic osteomyelitis. Assessing the quality of randomized controlled trials. or adverse events between the compared regimens. Rev Esp Quimioter 1999. the methodology of randomization helps decrease the misbalance of the aforementioned and other confounders between the compared treatment groups. 17. Gentry LO. Bryant RE.282:260 – 6.282: 316 –22. although such data would be useful to be reported and taken under consideration in the interpretation and generalizibility of the findings of the meta-analysis. Lipsky BA. fluoroquinolones proved as effective as ␤-lactams for the treatment of osteomyelitis. . therapeutic considerations and unusual aspects (second of three parts). Hooper DC. bacteriological success. et al. 13. 10. et al. Meta-analysis in clinical trials. ● Seven eligible trials were included in our metaanalysis. Am J Med 1989. Comparative pharmacokinetics of ofloxacin and ciprofloxacin. Stengel D. 9. 15. Tugwell P. Wolfson JS. Control Clin Trials 1986. Wolfson JS. they should be used with caution and according to the resistance patterns of the pathogens in each setting.24:643– 8. McGowan K. N Engl J Med 1970. Effect of the abscess environment on the antimicrobial activity of ciprofloxacin.87:31S–36S.