1 C.H. de Versailles, Microbiologie, Le Chesnay; 2 Université Paris 5, Microbiologie, Paris, France
Keywords: Bordetella pertussis, gatifloxacin, erythromycin, quinolones
Sir,
Pertussis, commonly known as whooping cough, is a highly contagious acute infection of the respiratory tract mainly due to Bordetella pertussis. However, despite high vaccination rates, pertussis remains epidemic and endemic in most industrial countries.1 The incidence of pertussis shows two peaks: one in infants <6 months old,2 the other in teenagers and adults.1 The cause of this increase is not clearly known; however, it may be due to increased accuracy of diagnosis, better reporting of the disease and decline in immunity over time. Furthermore, in a population with high incidence of vaccination, the disease does not frequently follow the classical course and is often misdiagnosed. This is particularly so in adults, in whom the disease may go unrecognized. Adults and teenagers, with a long-term, persistent cough, are often infected with B. pertussis. The adults can act as a reservoir of pertussis infection, passing it to infants and young children. Bourgeois et al.2 found that 37% of infections in children were acquired from their parents.
Traditionally B. pertussis has been susceptible to most antimicrobial agents, including erythromycin, which is the drug of choice for treatment and post-exposure prophylaxis of B. pertussis infection. Fluoroquinolones are currently recommended for the treatment of respiratory tract infections in adult patients. Gatifloxacin is a novel 8-methoxyquinolone with potent activity against both Gram-negative and -positive bacteria.3 In this study we evaluated the in vitro antimicrobial activity of gatifloxacin, ciprofloxacin and levofloxacin against 51 recent clinical isolates, including 12 erythromycin-resistant strains of B. pertussis.
Strains of B. pertussis were recovered from nasopharyngeal specimens taken from children and adults at Versailles Hospital (n = 23) and Pellegrin Hospital (n = 15), Bordeaux, France. Thirteen strains came from the USA, including 12 resistant to erythromycin.4
An agar dilution method was used to determine the MIC of each antibiotic. Serial concentrations of antibiotics were incorporated into MuellerHinton agar supplemented with 10% horse blood (Bio-Rad). Inocula were applied with a Steers replicator, resulting in a final inoculum of 104105 cfu/spot. The plates were incubated for 3 days at 36°C without carbon dioxide, and were protected from desiccation. Antibiotic-free plates were inoculated before and after the test plates to check for growth and purity. Staphylococcus aureus ATCC 25923 and B. pertussis ATCC 9797 served as control strains.
All French strains were susceptible to erythromycin (MICs 0.03 mg/L). Erythromycin MICs for the resistant USA strains were 1281024 mg/L. All strains, both erythromycin susceptible and resistant, appeared to be susceptible to gatifloxacin (MIC90 0.125 mg/L), ciprofloxacin (MIC90 0.06 mg/L) and levofloxacin (MIC90 0.06 mg/L).
Erythromycin remains the antibiotic of choice for B. pertussis infections. Since 1994, the emergence of macrolide resistance in clinical isolates has been reported in the USA.5 Mutations in the peptidyl region of 23S rRNA may confer macrolide resistance.4 To our knowledge, no erythromycin-resistant B. pertussis has been isolated so far in Europe.
Fluoroquinolones are currently recommended for the treatment of respiratory tract infections in adult patients, which is usually empirical. Newer fluoroquinolones have improved activity against important Gram-positive respiratory tract pathogens relative to earlier agents (ciprofloxacin and ofloxacin) and have a profile of in vitro activity that includes the majority of bacterial respiratory pathogens. Whooping cough appeared to be a common cause of persistent cough in adults.1 Several fluoroquinolones showed good in vitro activity against Bordetella and achieved concentrations in respiratory secretions that were well above their MICs.3,6 The three fluoroquinolones tested (ciprofloxacin, levofloxacin and gatifloxacin) all had potent activity against B. pertussis. In our study, the new fluoroquinolone gatifloxacin was as active as ciprofloxacin and levofloxacin against erythromycin-susceptible and -resistant strains. The activity of the three fluoroquinolones observed in this study is similar to that obtained in other studies on susceptible strains of B. pertussis.3,6,7 Gatifloxacin is known to exhibit a good in vitro activity against bacteria responsible for community-acquired respiratory tract infections, including atypical pathogens such as Mycoplasma pneumoniae, Legionella pneumophila and Chlamydia pneumoniae, and B. pertussis could be added to this list.3 So fluoroquinolones used empirically would cover unexpected and misdiagnosed B. pertussis infection in adults. However, a good activity against B. pertussis in vitro does not guarantee clinical success, which depends especially on the antimicrobial bronchopulmonary concentration. Fluoroquinolones have shown good penetration into respiratory tract, producing levels that are greatly in excess of inhibitory levels required for B. pertussis,8 although there are no supporting clinical data at present.
In summary, the fluoroquinolones gatifloxacin, ciprofloxacin and levofloxacin could be effective in the treatment of pertussis in adults. They could also offer an alternative to macrolide therapy, especially against erythromycin-resistant B. pertussis infection or prophylaxis in adults. Moreover, broader spectrum fluoroquinolones used empirically as monotherapy for lower respiratory tract infection would cover unexpected B. pertussis in adults.
Acknowledgements
We thank F. Megraud and G. S. Sanden for providing clinical isolates. This study was supported by a grant from Grünenthal.
Footnotes
* Corresponding author. Tel: +33-1-39-63-87-51; Fax: +33-1-39-63-93-12; E-mail: fdp{at}fc.horus-medical.fr
References
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