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Jean-Winoc Decousser, Imen Methlouthi, Patrick Pina, Pierre Allouch, on behalf of The ColBVH Study, In vitro activity of ertapenem against bacteraemic pneumococci: report of a French multicentre study including 339 strains, Journal of Antimicrobial Chemotherapy, Volume 55, Issue 3, March 2005, Pages 396–398, https://doi.org/10.1093/jac/dki019
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Sir,
Streptococcus pneumoniae is the most common cause of infections of the lower respiratory tract in adults and children. In Europe, France has the highest rates of penicillin and erythromycin resistance in pneumococci: in 2002, 53% and 58% of the strains were found to be non-susceptible to these antibiotics, respectively.1 In American guidelines (but not in French guidelines), ertapenem, a newly licensed parenteral carbapenem, constitutes an alternative to the usual parenteral β-lactams for inpatients with pneumococcal infection.2 The purpose of this national multicentre study was to report the in vitro susceptibility to ertapenem and comparator compounds of S. pneumoniae isolated from French adults suffering from bacteraemic pneumonia.
Between 2000 and 2003, 339 strains of S. pneumoniae were collected by The ColBVH Study Group, a network of 105 non-teaching hospitals representative of general hospitals in France. These non-duplicated isolates were from blood cultures from hospitalized adults with pneumonia and were sent to a central laboratory (Service d'Hygiène, Centre Hospitalier de Versailles). The MICs of ertapenem, and penicillin G, amoxicillin, cefuroxime, cefotaxime, ceftriaxone, imipenem, erythromycin, quinupristin/dalfopristin, linezolid, levofloxacin, gatifloxacin and moxifloxacin, were determined using the agar dilution method in ambient air and interpreted according to NCCLS guidelines.3S. pneumoniae ATCC 49619 was used as a control strain.
Among the 339 pneumococci tested, 92 (27.1%) and 55 (16.3%) were penicillin-intermediate and -resistant, respectively (Table 1). Ceftriaxone, ertapenem, imipenem, linezolid and quinupristin/dalfopristin were constantly active, although the MIC90 of the first three compounds increased with penicillin resistance: 1, 0.25 and 0.125 mg/L for penicillin-resistant strain versus 0.016, 0.016 and 0.008 mg/L for penicillin-susceptible strains, respectively. In terms of percentage of full susceptible strains, ranking of β-lactams was: ertapenem = imipenem = ceftriaxone > amoxicillin > cefotaxime > cefuroxime > penicillin. Unlike cefuroxime, the in vitro activity of amoxicillin or cefotaxime remained high even amongst high-level penicillin-resistant strains. The percentage of erythromycin-susceptible strains decreased dramatically amongst penicillin non-susceptible isolates (88.5%, 17.4% and 3.6% of penicillin-susceptible, penicillin-intermediate and high-level penicillin-resistant pneumococci, respectively). Fluoroquinolones with enhanced activity against S. pneumoniae showed high in vitro activity (99.4% of susceptible strains).
Owing to the widespread occurrence of multidrug-resistant clones of S. pneumoniae, broad-spectrum cephalosporins combined with a macrolide and respiratory fluoroquinolones are now recommended for antibiotic therapy of severe pneumococcal infections.2 Ertapenem, which showed high in vitro and clinical efficiency against the main respiratory pathogens, could constitute an alternative antibiotic therapy.2,4 In this study, we have presented data concerning the ertapenem susceptibility of French bacteraemic isolates of S. pneumoniae. In terms of MIC90, this new compound seems to be at least as effective as ceftriaxone, the main comparator for the therapy of severe community-acquired pneumonia. These findings confirm data from previous studies.4 Nevertheless, the lack of ertapenem-intermediate or -resistant strains contrasts with the 40% of resistant strains amongst penicillin-resistant isolates reported in a recent Italian study.4 This dramatic discrepancy could probably be explained by the phenotypic characteristics of the penicillin-resistant isolates described here, which remained susceptible to third-generation cephalosporins. Amoxicillin, which showed high in vitro activity against pneumococci, could not be used in the empirical antibiotic therapy of severe pneumonia as the antimicrobial spectrum of this compound does not include β-lactamase-positive Haemophilus influenzae and Moraxella catarrhalis strains, two important agents of respiratory tract infections.4 Although cefuroxime and erythromycin were theoretically both active against S. pneumoniae, these agents are not recommended for empirical use in patients with severe pneumococcal infections. To date, imipenem, linezolid and quinupristin/dalfopristin were considered as second-line agents for multiresistant nosocomial bacteria and were not indicated in the antibiotic therapy of severe community-acquired lower respiratory tract infections. So the choice of empirical therapy of severe inpatient pneumonia was limited to third-generation cephalosporins (combined with a macrolide) or to an antipneumococcal fluoroquinolone. Concerning this last antibiotic class, some concerns have been raised regarding (i) the capacity of the phenotypic methods to detect first step mutants in S. pneumoniae and (ii) the role of prior quinolone use as a risk factor for subsequent infection with methicillin-resistant Staphylococcus aureus or quinolone-resistant Gram-negative bacilli.5,6 In the same way, the use of third-generation cephalosporins selects extended-spectrum β-lactamase-producing Klebsiella species.5 This ‘collateral damage’ as named by Paterson5 should be avoided with the use of ertapenem which is not hydrolysed by this kind of enzyme. Other investigational or licensed drugs such as faropenem or ketolides should be studied as comparator agents. However, for the time being, no parenteral formulation of these antibiotics is available. In summary, this study underlines the potential significant contribution of ertapenem in the parenteral therapy of bacteraemic pneumococcal pneumonia in France.
Activity of antibiotics against 339 isolates of Streptococcus pneumoniae
| . | . | . | . | Antibiotic susceptibilities . | . | . | ||
|---|---|---|---|---|---|---|---|---|
| Antimicrobial agents . | MIC50 (mg/L) . | MIC90 (mg/L) . | Range of MICs (mg/L) . | %S . | %I . | %R . | ||
| Penicillin | 0.032 | 2 | 0.008–4 | 56.6 | 27.1 | 16.3 | ||
| Amoxicillin | 0.032 | 1 | 0.008–4 | 98.8 | 1.2 | 0 | ||
| Cefuroxime | 0.064 | 4 | 0.008–16 | 62.2 | 3.2 | 34.6 | ||
| Cefotaxime | 0.032 | 1 | 0.008–4 | 96.8 | 2.9 | 0.3 | ||
| Ceftriaxone | 0.016 | 0.5 | 0.008–1 | 100 | 0 | 0 | ||
| Ertapenem | 0.016 | 0.25 | 0.008–1 | 100 | 0 | 0 | ||
| Imipenem | 0.008 | 0.125 | 0.008–0.125 | 100 | 0 | 0 | ||
| Erythromycin | 0.25 | 512 | 0.064–512 | 55.5 | 0 | 44.5 | ||
| Quinupristin/dalfopristin | 0.25 | 1 | 0.25–1 | 100 | 0 | 0 | ||
| Linezolid | 1 | 1 | 0.5–2 | 100 | 0 | 0 | ||
| Levofloxacin | 1 | 2 | 0.25–8 | 99.4 | 0 | 0.6 | ||
| Gatifloxacin | 0.25 | 0.5 | 0.032–8 | 99.4 | 0 | 0.6 | ||
| Moxifloxacin | 0.125 | 0.25 | 0.016–4 | 99.4 | 0 | 0.6 | ||
| . | . | . | . | Antibiotic susceptibilities . | . | . | ||
|---|---|---|---|---|---|---|---|---|
| Antimicrobial agents . | MIC50 (mg/L) . | MIC90 (mg/L) . | Range of MICs (mg/L) . | %S . | %I . | %R . | ||
| Penicillin | 0.032 | 2 | 0.008–4 | 56.6 | 27.1 | 16.3 | ||
| Amoxicillin | 0.032 | 1 | 0.008–4 | 98.8 | 1.2 | 0 | ||
| Cefuroxime | 0.064 | 4 | 0.008–16 | 62.2 | 3.2 | 34.6 | ||
| Cefotaxime | 0.032 | 1 | 0.008–4 | 96.8 | 2.9 | 0.3 | ||
| Ceftriaxone | 0.016 | 0.5 | 0.008–1 | 100 | 0 | 0 | ||
| Ertapenem | 0.016 | 0.25 | 0.008–1 | 100 | 0 | 0 | ||
| Imipenem | 0.008 | 0.125 | 0.008–0.125 | 100 | 0 | 0 | ||
| Erythromycin | 0.25 | 512 | 0.064–512 | 55.5 | 0 | 44.5 | ||
| Quinupristin/dalfopristin | 0.25 | 1 | 0.25–1 | 100 | 0 | 0 | ||
| Linezolid | 1 | 1 | 0.5–2 | 100 | 0 | 0 | ||
| Levofloxacin | 1 | 2 | 0.25–8 | 99.4 | 0 | 0.6 | ||
| Gatifloxacin | 0.25 | 0.5 | 0.032–8 | 99.4 | 0 | 0.6 | ||
| Moxifloxacin | 0.125 | 0.25 | 0.016–4 | 99.4 | 0 | 0.6 | ||
Activity of antibiotics against 339 isolates of Streptococcus pneumoniae
| . | . | . | . | Antibiotic susceptibilities . | . | . | ||
|---|---|---|---|---|---|---|---|---|
| Antimicrobial agents . | MIC50 (mg/L) . | MIC90 (mg/L) . | Range of MICs (mg/L) . | %S . | %I . | %R . | ||
| Penicillin | 0.032 | 2 | 0.008–4 | 56.6 | 27.1 | 16.3 | ||
| Amoxicillin | 0.032 | 1 | 0.008–4 | 98.8 | 1.2 | 0 | ||
| Cefuroxime | 0.064 | 4 | 0.008–16 | 62.2 | 3.2 | 34.6 | ||
| Cefotaxime | 0.032 | 1 | 0.008–4 | 96.8 | 2.9 | 0.3 | ||
| Ceftriaxone | 0.016 | 0.5 | 0.008–1 | 100 | 0 | 0 | ||
| Ertapenem | 0.016 | 0.25 | 0.008–1 | 100 | 0 | 0 | ||
| Imipenem | 0.008 | 0.125 | 0.008–0.125 | 100 | 0 | 0 | ||
| Erythromycin | 0.25 | 512 | 0.064–512 | 55.5 | 0 | 44.5 | ||
| Quinupristin/dalfopristin | 0.25 | 1 | 0.25–1 | 100 | 0 | 0 | ||
| Linezolid | 1 | 1 | 0.5–2 | 100 | 0 | 0 | ||
| Levofloxacin | 1 | 2 | 0.25–8 | 99.4 | 0 | 0.6 | ||
| Gatifloxacin | 0.25 | 0.5 | 0.032–8 | 99.4 | 0 | 0.6 | ||
| Moxifloxacin | 0.125 | 0.25 | 0.016–4 | 99.4 | 0 | 0.6 | ||
| . | . | . | . | Antibiotic susceptibilities . | . | . | ||
|---|---|---|---|---|---|---|---|---|
| Antimicrobial agents . | MIC50 (mg/L) . | MIC90 (mg/L) . | Range of MICs (mg/L) . | %S . | %I . | %R . | ||
| Penicillin | 0.032 | 2 | 0.008–4 | 56.6 | 27.1 | 16.3 | ||
| Amoxicillin | 0.032 | 1 | 0.008–4 | 98.8 | 1.2 | 0 | ||
| Cefuroxime | 0.064 | 4 | 0.008–16 | 62.2 | 3.2 | 34.6 | ||
| Cefotaxime | 0.032 | 1 | 0.008–4 | 96.8 | 2.9 | 0.3 | ||
| Ceftriaxone | 0.016 | 0.5 | 0.008–1 | 100 | 0 | 0 | ||
| Ertapenem | 0.016 | 0.25 | 0.008–1 | 100 | 0 | 0 | ||
| Imipenem | 0.008 | 0.125 | 0.008–0.125 | 100 | 0 | 0 | ||
| Erythromycin | 0.25 | 512 | 0.064–512 | 55.5 | 0 | 44.5 | ||
| Quinupristin/dalfopristin | 0.25 | 1 | 0.25–1 | 100 | 0 | 0 | ||
| Linezolid | 1 | 1 | 0.5–2 | 100 | 0 | 0 | ||
| Levofloxacin | 1 | 2 | 0.25–8 | 99.4 | 0 | 0.6 | ||
| Gatifloxacin | 0.25 | 0.5 | 0.032–8 | 99.4 | 0 | 0.6 | ||
| Moxifloxacin | 0.125 | 0.25 | 0.016–4 | 99.4 | 0 | 0.6 | ||
The Collège de Bactériologie-Virologie Hygiène des Hôpitaux (ColBVH) Study Group participants are listed in the Acknowledgements.
We received no funding from any pharmaceutical manufacturers.
We thank the microbiologists who participated in The ColBHV Study Group: J. Akli (Blois), C. Alba-Sauviat (Chaumont), G. Aubert (Saint Etienne), Amirault (Vierzon), J. Assens (St Afrique), J. P. Aubry (Quimperle), P. Aucher (Saint Jean D'angely), C. Auvray (Charleville Mezieres), A. Bailly (Albi), A. Barrans (Sete), D. Barraud (Gonesse), C. Benoit (Fontainebleau), E. Bichier (Saumur), H. Biessy (La Rochelle), M. Bietrix (Martigues), P. Bineau (Saint Dizier), V. Blanc (Antibes), S. Bland (Annecy), A. Boisivon (St Germain en Laye), Y. Boucaud-Maitre (Lyon), C. Bouguigny-Saison (Soissons), P. Brisou (Toulon Naval), S. Brovedani (Rambouillet), M. Caillaux (Tourcoing), B. Cancet (Villeneuve sur Lot), J. Carre-Cavelier (Bayeux), G. L. Cartolano (St Germain En Laye), J. Cartron (Dreux), G. Chambreuil (La Roche sur Yon), P. Chantelat (Vesoul), A. Chapelle (Aubenas), C. Chaplain (Saint Denis), H. Chardon (Aix En Provence), B. Chaurang (Neuilly Sur Seine), A. Clarac (Foix), P. Clergeau (Sallanches), E. Collot (Bar Le Duc), P. Courrier (Metz Armees), M. F. Danjoux (Tarbes), J. P. Darchis (Compiegne), H. De Montclos (Bourg En Bresse), A. Decoster (Lomme Les Lille), C. Delamare (Thionville), J. M. Delarbre (Mulhouse), P. Deligne (Remiremont), F. Delubac (Annonay), M. C. Demachy (Meaux), H. Demontclos (Bourg en Bresse), J. Deregnaucourt (Paris), M. A. Desailly-Chanson (La Roche Sur Yon), J. Didion (Metz), F. Doucet-Populaire (Versailles), A. Dublanchet (Villeneuve St Georges), B. Dubourdieu (Rodez), S. Dubourdieu (Gisors), Dupond (Laon), C. Durand (Provins), C. Eloy (Troyes), P. Emerique (Remiremont), F. Evreux (Le Havre), D. Fevre (Vienne), J. Flipo (Wissembourg), N. Fonsale (St Etienne), A. Fremaux (Creteil), C. Fuhrmann (Lyon), S. Gabriel (Monaco), M. Galanti (Coulommiers), G. Gallou (Falaise), F. Gandhilhon-Crepet (Monbrison), I. Ganivala (Montauban), E. Gardien (Morlaix), Garnotel (Marseille-Armees), M. Gavignet (Bourges), F. Geffroy (Quimper), C. Grasmick (Cahors), B. Gravagna (Lyon), G. Grise (Elbeuf), C. Guier (St Valler), P. Guiet (Nemours), A. Heidt (Hagueneau), M. Helfre (Firminy), J. Heurte (Beauvais), E. Heusse (Bayeux), M. C. Jaffar Bandjee (Saint Denis Reunion), D. Jan (Laval), E. Jaouen (Sable Sur Sarthe), G. Khatib (Bagnols Sur Ceze), J. P. Lafargue (Dax), R. Lamarca (Narbonne), V. Larroque (Carcassonne), E. Laurens (Cholet), A. Le Coustumier (Cahors), F. Le Turdu (Argenteuil), J. Y. Leberre (Saint Nazaire), E. Lecaillon Thibon (Perpignan), H. Lefrand-Crepin (Avignon), P. Lemaitre (Creil), C. Lemble (Selestat), M. Leneveu (Meulan), Lepilleur (St Dizier), A. Mandjee (Romans), A. Mangeol (Montfermeil), M. F. Marchal (Annemasse), M. Marcolin (Arras), A. Marmonier (Le Mans), T. Masseron (Lyon Cedex 03), R. Meley (Saint Etienne), O. Menouni (Montceau les Mines), M. Menouar (Rang Du Flier), A. Michel (Marseille), M. Mora (Frejus), B. Moreau (Cayenne), A. Morel (Le Havre), O. Morvan (Saint Brieuc), D. Neri Schiavini (Cannes), G. Otterbein (Bry Sur Marne), X. Palette (Plaisir), B. Pangon (Versailles), J. Paul (Boulogne sur Mer), C. Payen (Brignoles), M. Perrin (Thionville), D. Pierrejean (Auch), P. Pouedras (Vannes), D. Pressac (Tulle), G. Rast (Poissy), D. Reisz (Montceau les Mines), F. Richardin (Mantes La Jolie), Y. Rio (Metz), P. Roos (Thionville), P. Roussellier (Salon De Provence), Rousset (Beaune), M. Rouviere (Mende), O. Sabot (Belley), Saly (St Denis de la Réunion), S. Samaille (Saint Omer), R. Sanchez (Perigueux), A. Scanvic (Argenteuil), Y. Scat (Paris), A. Secher (Chartres), H. Sep-Hieng (Avranches), D. P. Simeon (Langres), V. Simha (Hyeres), C. Sire-Bidault (Chalon sur Saone), Smati (Aubenas), A. Sommabere (Brive), P. Stoessel (Neufchateau), P. Stolidi (Aubagne), F. Templier (Armentieres), J. P. Thellier (Chateau Thierry), Thore (Beaune), J. Tous (Chambery), A. Trevoux (Mulhousse), A. Vachee (Roubaix), E. Vallee (Eaubonne), J. Vaucel (St Brieuc), A. Verhaeghe (Dunkerque), M. Villemain (Aurillac), M. Viot (Nice), I. Vray (Voiron), J. F. Ygout (Lorient).
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Author notes
1Service d'Hygiène Hospitalière, Centre Hospitalier de Versailles André Mignot, 177 rue de Versailles, 78150 Le Chesnay; 2Equipe Opérationnelle d'Hygiène, Laboratoire de Biologie, Centre Hospitalier de Dourdan, 2 rue du Potelet, 91415 Dourdan; 3Service de Médecine B, Hôpital de Plaisir Grignon, 220 rue Mansart, 78375 Plaisir, France
