View metadata, citation and similar papers at core.ac.uk brought to you by CORE

Paperprovided by 57Elsevier Disc - Publisher Connector

Antimicrobial therapy of infections with aerobic Gram-positive rods

A. von Graevenitz

Department of Medical Microbiology, University of Zurich, Switzerland

ABSTRACT This review presents data on in vitro susceptibilities of aerobically growing Gram-positive rods and in vivo activities of used against Gram-positive rods. While in some instances susceptibility and efficacy are predictable (e.g. vs. Listeria and microaerophilic coryneforms, or metronidazole vs. Gardnerella) susceptibility testing by dilution techniques seems necessary for many Gram-positive rods as long as they are deemed clinically relevant. Clin Microbiol Infect 2001: 7 (Supplement 4): 43±46

caused by aerobic (i.e. aerobically growing) Gram-positive INTRODUCTION rods, without covering dosage and duration of therapy. Infections with Gram-positive rods are rare in comparison with those caused by Gram-positive cocci or Gram-negative Ahed Bacillus spp. rods. Gram-positive rods do not often figure in Bhed susceptibility studies, and very few, if any, large-scale or Gram-positive spore-forming rods are frequent contaminants Ched controlled clinical studies with these organisms are available. of cultures but may cause serious infections such as septicemia, Dhed Only anecdotal experience exists for many antimicrobials. endocarditis, endophthalmitis and wound infections. Bacillus Ref marker Some of these infections may require additional surgical cereus, the most frequent species, is resistant to b-lactam Fig marker intervention (e.g. actinomycosis, infections involving prosthe- antibiotics [4]. It has been treated successfully with clindamy- Table marker tic material), local (e.g. intravitreal, intravaginal) or prolonged cin, ciprofloxacin, vancomycin and imipenem [4±7]. Food Ref end treatment (e.g. in nocardiosis). Approved NCCLS standar- poisoning resulting from this bacillus does not require Ref start dized disk susceptibility testing data and breakpoints are not, as antibiotic treatment. Resistance to penicillin and clindamycin yet, available for any Gram-positive rods. One study found may occur in other Bacillus species, and is common to third- excellent correlations between the results of microdilution and generation cephalosporins [4,5]. Susceptibility testing is thus disk susceptibility testing of corynebacteria if the NCCLS required for clinically relevant strains. It should be noted that streptococcal criteria for and vancomycin and Bacillus circulans may carry the vanA gene [8]. the Listeria criteria for penicillin [1] were used [2]. Another Bacillus anthracis has, thus far, remained susceptible to penicillin study found few discrepancies for Corynebacterium jeikeium if [9], although an increase in MIC has recently been reported in interpretative criteria for enterococci were applied [3]. Some one publication [10]. Ciprofloxacin has been used as an Gram-positive rods have predictable susceptibilities to certain alternative to penicillin for treatment and prophylaxis [11]. antimicrobials, e.g. to penicillin; however, a correct species or at least genus diagnosis is required before assuming predictable Aerobic coryneform activity for pathogens such as Corynebacterium diphtheriae, spp., Propionibacterium acnes or dentocariosa. If coryneform bacteria are isolated in pure culture from The average laboratory may find this task difficult to normally sterile sites or if they predominate in cultures from accomplish. Dilution tests remain the standard at present. the lower respiratory or urinary tracts or from deep wounds, This paper will review the activity of antimicrobials with their possible pathogenic role should be evaluated carefully. A regard to susceptibility testing and treatment of infections species diagnosis may be useful in predicting susceptibility or resistance. Corresponding author and reprint requests: A. von Graevenitz, Corynebacterium diphtheriae should, of course, always be Gloriastrasse 32, Zurich, Switzerland identified to species and tested for toxigenicity. For toxigenic Tel: +41 1634 2622 Fax: +41 1634 4906 strains, antitoxin must be administered, and antibiotics should E-mail: [email protected] be given to interrupt the production of toxin as well as the

# 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 7 (Suppl. 4), 43±46 Paper 57 Disc

44 Clinical Microbiology and Infection, Volume 7, Supplement 4, 2001

spread to other individuals. Nontoxigenic strains that do not been no clinical experience with other quinolones, in spite of require antitoxin for treatment have become particularly their in vitro activity [33]. Surgery may be necessary in cases of frequent in the recent past as agents of endocarditis and soft- abscess formation, ocular or prosthetic infections. If Actinoba- tissue infections in intravenous drug abusers and in the cillus actinomycetemcomitans is involved in actinomycosis, homeless [12,13]. Penicillin resistance has not been observed, effective therapy may also require ciprofloxacin [34], although and penicillin remains the drug of choice over erythromycin opinions vary [25]. to which a few strains have become resistant [14]. This fact should be taken into account when erythromycin is Gardnerella vaginalis considered for the eradication of the carrier state, for which indication it seems to be more effective than penicillin [15]. Most researchers in the field assume that Gardnerella vaginalis Although numerous reports of infections with other species has a role in bacterial vaginosis [35]. Although susceptible to of corynebacteria exist, their treatment has not been many antibiotics [35], metronidazole is the drug of choice for thoroughly evaluated. Individual reports suggest that dilution vaginosis; the hydroxy metabolite being the active agent [35]. susceptibility results are good predictors for the success of An alternative is clindamycin, which, like metronidazole, may therapy. The most frequent species, C. amycolatum, C. striatum, also be applied by the intravaginal route, although not in the C. jeikeium, C. urealyticum, C. minutissimum and C. pseudo- first trimester of pregnancy. The optimal treatment for diphtheriticum, show variable susceptibilities [16±19] and must nonvaginal infections has not been determined as yet but b- be tested individually. Only C. pseudodiphtheriticum has so far lactams have been suggested [35]. been uniformly susceptible to penicillin [16]. For species intrinsically resistant to multiple antibiotics such as C. jeikeium Lactobacillus species or C. urealyticum acillus, vancomycin or teicoplanin may be the only antibiotics effective in vitro and in vivo [17±19]. Various Lactobacilli have been increasingly reported as agents of ketolides have shown activity against macrolide-resistant human infections, presumably due to improved diagnostic strains of corynebacteria, but their activity against C. jeikeium capabilities of clinical laboratories. Most strains are still and C. urealyticum has been variable [20,21]. Further data on susceptible to penicillin but a few have become resistant infections and susceptibilities of corynebacteria can be found [36,37]. Of note is the frequent resistance to vancomycin in several recent reviews [17±21]. which is species-dependent, Lactobacillus rhamnosus being Experience in treating noncorynebacterial coryneforms, e.g. resistant and Lactobacillus acidophilus being susceptible [37]. species of Aureobacterium/Microbacterium, Cellulomonas, Arthro- Clindamycin and erythromycin have also been used ther- bacter, Leifsonia, Oerskovia, Dermabacter, Brevibacterium and apeutically. In systemic infections such as endocarditis, the Turicella, is even more limited [17]. Susceptibility tests are combination of penicillin plus an has been necessary, particularly since resistance to vancomycin (but not effective [36]. to teicoplanin) has been noted in strains of Aureobacterium [22± 24] and Leifsonia aquatica (`Corynebacterium aquaticum') [24]. Erysipelothrix rhusiopathiae

Erysipelothrix rhusiopathiae is vancomycin-resistant but suscep- Microaerophilic/anaerobic coryneforms tible to penicillin and other b-lactams that are used to treat This group of bacteria includes species of Actinomyces, erysipeloid and the rare systemic infections [38]. No published Propionibacterium, Arcanobacterium and Rothia. It is discussed large-scale experience is available for infections occurring in here because many strains will eventually grow in ambient air, penicillin-allergic patients. and because Rothia dentocariosa may appear as a rod. Experience in the therapy of infections caused by the first two genera is Listeria monocytogenes more extensive than with the others [25±32]. Thus far, all genera have remained susceptible to penicillin and other b- The literature on antimicrobial susceptibilities and treatment lactam antibiotics [25±32], penicillin being the drug of choice. of infections caused by Listeria monocytogenes is rather extensive For penicillin-allergic patients, clindamycin and [39]. So far, all strains isolated have remained susceptible to have been employed [25]. For R. dentocariosa endocarditis, penicillin or ampicillin, while most are resistant to the treatment with a combination of vancomycin and cephalosporins. Penicillin or ampicillin plus gentamicin are has been recommended [32]. the preferred drugs for treatment. In penicillin-allergic Metronidazole as well as and first-and patients, cotrimoxazole is recommended. Strains resistant to second-generation fluoroquinolones are ineffective. There has , erythromycin, clindamycin, streptomycin

# 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 7 (Suppl. 4), 43±46 Paper 57 Disc

von Graevenitz Infections with Gram-positive rods 45

and have occasionally been observed [40]. Listeria), each isolate of possible clinical significance should be Vancomycin is active in vitro but unreliable in treating tested for susceptibility. CAPD peritonitis [41]. REFERENCES Aerobic actinomycetes 1. National Committee for Clinical Laboratory Standards. Performance standards Treatment of infections caused by aerobic actinomycetes for antimicrobial disk susceptibility tests. M2±A5. Villanova, PA: National Committee for Clinical Laboratory Standards, 1993. should improve as standardized methods for diagnosis and 2. Weiss K, Laverdiere M, Rivest K. Comparison of antimicrobial susceptibility testing are developed [42]. These procedures are susceptibilities of Corynebacterium species by broth microdilution and disk particularly important for nocardial infections because diffusion methods. Antimicrob Agents Chemother 1996; 40: 930±3. farcinica, N. transvalensis and N. otitidiscaviarum are, unlike N. 3. Traub WH, Geipel U, Leonhard B, Bauer D. Antibiotic susceptibility asteroides,frequently resistant to third-generation cephalospor- testing (agar disk diffusion and agar dilution) of clinical isolates of ins [43±45], N. transvalensis may be amikacin-resistant [43], Corynebacterium jeikeium. Chemotherapy 1998; 44: 230±7. 4. Weber DJ, Saviteer SM, Rutala WA, Thomann CA. In vitro susceptibility and N. transvalensis and N. farcinica may even be resistant to of Bacillus spp. to selected antimicrobial agents. Antimicrob Agents Chemother cotrimoxazole [43±46]. 1988; 32: 642±5. Sulfonamides with or without trimethoprim are otherwise 5. Banerjee C, Bustamante CI, Wharton R, Talley E, Wade JC. Bacillus standard therapeutic agents for nocardiosis [45]. Alternatives infections in patients with cancer. Arch Intern Med 1988; 148: 1769±74. include imipenem plus amikacin or, in N. asteroides, this 6. Steen MK, Bruno-Murtha LA, Chaux G, Lazar H, Bernard S, Sulis C. Bacillus cereus endocarditis. report of a case and review. Clin Infect Dis 1992; combination plus cefotaxim or ceftriaxone. More rarely, 14: 945±6. depending on susceptibility testing results, minocycline or 7. Kemmerly SA, Pankey GA. Oral ciprofloxacin therapy for Bacillus cereus amoxicillin-clavulanic acid has been employed [45]. Duration wound infection and bacteremia. Clin Infect Dis 1993; 16: 189. of treatment depends on organ localization and extent of the 8. Fontana R, Ligozzi M, Pedrotti C, Padovani EM, Cornaglia G. infection [44]. A recent study showed the ketolide, linezolid, Vancomycin-resistant Bacillus circulans carrying the vanA gene responsible for vancomycin resistance in enterococci. Eur J Clin Microbiol Infect Dis to be active against many nocardial species [47], but its clinical 1997; 16: 473. effectiveness remains to be determined. 9. Doganay M, Aydin N. Antimicrobial susceptibility of Bacillus anthracis. For infections caused by Actinomadura, amikacin in Scand J Infect Dis 1991: 333±5. combination with cotrimoxazole has been recommended 10. Lalitha MK, Thomas MK. Penicillin resistance in Bacillus anthracis. Lancet [48]. The optimal treatment for Gordona and Tsukamurella 1997; 349: 1522. 11. Friedlander AM, Welkos SL, Pitt MLM et al Postexposure prophylaxis infections has not been established due to the paucity of cases. against experimental inhalation anthrax. J Infect Dis 1993; 167: 1239±42. For Dermatophilus congolensis, penicillin combined with 12. Belko J, Wessel DL, Malley R. Endocarditis caused by Corynebacterium streptomycin seems to be the treatment of choice [45]. diphtheriae. Case report and review of the literature. Pediatr Infect Dis J 2000; For the more common infections with rhodococci, 19: 159±63. particularly with R. equi, the optimal treatment regimen is 13. Funke G, Altwegg M, Frommelt L, von Graevenitz A. Emergence of nontoxigenic Corynebacterium diphtheriae biotype mitis strains in Western also still unknown [49±51]. The organism occurs both extra- Europe. Emerg Infect Dis 1999; 5: 477±80. and intracellularly, often as an opportunist in HIV-infected 14. Kneen R, Giao PN, Van Solomon TTTM et al Penicillin vs. erythromycin individuals. Combination therapies using drugs to which most in the treatment of diphtheria. Clin Infect Dis 1998; 27: 845±50. strains are susceptible in vitro [51], i.e. vancomycin combined 15. McCloskey RV, Green MJ, Eller J, Smilack J. Treatment of diphtheria with imipenem (for bacteremic cases) or erythromycin carriers: benzathine penicillin, erythromycin, and clindamycin. Ann Intern Med 1974; 81: 788±91. combined with rifampicin [50], have been recommended 16. Gutierrez-Rodero F, de la Tabla VO, Martinez C et al Corynebacterium although strains resistant to the latter two antibiotics have been pseudodiphtheriticum: an easily missed respiratory pathogen in HIV-infected observed, albeit rarely [51]. b-lactam agents should not be used patients. Diagn Microbiol Infect Dis 1999; 33: 209±16. [45]. Ketolides have shown variable activity in vitro. 17. Funke G, von Graevenitz A, Clarridge JE, Bernard KA. Clinical Regarding oxazolidinones, Linezolid is more active than microbiology of coryneform bacteria. Clin Microbiol Rev 1997; 10: 125±59. 18. Lagrou K, Verhaegen J, Janssens M, Wauters G, Verbist L. Prospective eperezolid [52]. Each isolate should be tested for susceptibility, study of catalase-positive coryneform organisms in clinical specimens: and treatment individualized accordingly. identification, clinical relevance, and antibiotic susceptibility. Diagn Microbiol Infect Dis 1998; 30: 7±15. 19. Funke G, Puenter V, von Graevenitz A. Antimicrobial susceptibility CONCLUSION patterns of some recently established coryneform bacteria. Antimicrob Agents Chemother 1996; 40: 2874±8. Aerobic Gram-positive rods do not present uniform in vitro 20. Martinez-Martinez L, Pascual A, Suarez AI, Perea EJ. In vitro activities of susceptibility patterns. Unless susceptibility and clinical efficacy ketolide HMR 3647, macrolides, and clindamycin against coryneform can be predicted from the species diagnosis (e.g. penicillin vs. bacteria. Antimicrob Agents Chemother 1998; 42: 3290±2.

# 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 7 (Suppl. 4), 43±46 Paper 57 Disc

46 Clinical Microbiology and Infection, Volume 7, Supplement 4, 2001

21. Jones RN, Johnson DM, Erwin ME. In vitro antimicrobial activities and species identification, H2O2 production, and antibiotic resistance spectra of U-100592 and U-100766, two novel fluorinated oxazolidinones. and correlation with human clinical status. J Clin Microbiol 1999; 37: Antimicrob Agents Chemother 1996; 40: 720±6. 729±33. 22. Nolte FS, Arnold KE, Sweat H, Winton EF, Funke G. Vancomycin- 38. Venditti M, Gelfusa V, Tarasi A, Brandimarte C, Serra P. Antimicrobial resistant Aureobacterium species cellulitis and bacteremia in a patient with susceptibilities of Erysipelothrix rhusiopathiae. Antimicrob Agents Chemother acute myelogenous leukemia. J Clin Microbiol 1996; 34: 1992±4. 1990; 34: 2038±40. 23. Funke G, Lawson PA, Nolte FS, Weiss N, Collins MD. Aureobacterium 39. Hof H, Nichterlein T, Kretschmar M. Management of listeriosis. Clin resistens sp. nov., exhibiting vancomycin resistance and teicoplanin Microbiol Rev 1997; 10: 345±57. susceptibility. FEMS Microbiol Lett 1998; 158: 89±93. 40. Charpentier E, Courvalin P. Antibiotic resistance in Listeria spp. Antimicrob 24. Funke G, von Graevenitz A, Weiss N. Primary identification of Agents Chemother 1999; 43: 2103±8. Aureobacterium spp. isolated from clinical specimens as `Corynebacterium 41. Banerji C, Wheeler DC, Morgan JR. Listeria monocytogenes CAPD Aquatum'. J Clin Microbiol 1994; 32: 2686±91. peritonitis. Failure of vancomycin therapy. J Antimicrob Chemother 1994; 25. Smego RA, Foglia G. Actinomycosis. Clin Infect Dis 1998; 26: 1255±63. 33: 374±5. 26. Sabbe L, van de Merwe D, Schouls L, Bergmans A, Vaneechoutte M, 42. National Committee for Clinical Laboratory Standards. Susceptibility testing Vandamme P. Clinical spectrum of infections due to the newly described of mycobacteria, Nocardia, and other aerobic actinomycetes; tentative standard, Actinomyces species A. turicensis, A. radingae, and A. europaeus. J Clin Microbiol M24±T2, 2nd edn. Villanova, PA: National Committee for Clinical 1999; 37: 8±13. Laboratory Standards, 2000. 27. Funke G, von Graevenitz A. Infections due to Actinomyces neuii (former 43. McNeil MM, Brown JM, Georghiu PR, Allworth AM, Blacklock Z. `CDC Coryneform Group 1' bacteria). Infection 1995; 23: 1±3. Infections due to Nocardia transvalensis. clinical spectrum and antimicrobial 28. Guerin-Faublee V, Flandrois J-P, Richard YG. Antimicrobial susceptibility therapy. Clin Infect Dis 1992; 15: 453±63. testing of Actinomyces pyogenes: comparison of disk diffusion test and API 44. Torres OH, Domingo P, Pericas R, Boiron P, Montiel JA, Vazquez G. ATB STREP system with the agar dilution method. Zentralbl Bakteriol Infection caused by Nocardia farcinica. case report and review. Eur J Clin 1993; 279: 377±86. Microbiol Infect Dis 2000; 19: 205±12. 29. Carlson P, Korpela J, Walder M, Nyman M. Antimicrobial susceptibilities 45. McNeil MM, Brown JM. The medically important actinomycetes. and biotypes of Arcanobacterium haemolyticum blood isolates. Eur J Clin epidemiology and microbiology. Clin Microbiol Rev 1994; 7: 357±417. Microbiol Infect Dis 1999; 18: 915±7. 46. Cohen E, Blickstein D, Inbar E, Samra Z, Weinberger M. Unilateral vocal 30. Brook I, Frazier EH. Infections caused by Propionibacterium species. Rev Infect cord paralysis as a result of a Nocardia farcinica laryngeal abscess. Eur J Clin Dis 1991; 13: 819±22. Microbiol Infect Dis 2000; 19: 224±7. 31. Jakab E, Zbinden R, Gubler J, Ruef C, von Graevenitz A, Krause M. 47. Brown-Elliott BA, Ward SC, Crist CJ, Mann LB, Wilson RW, Wallace RJ. Severe infections caused by Propionibacterium acnes: an underestimated In vitro activities of linezolid against multiple Nocardia species. Antimicrob pathogen in late postoperative infections. Yale J Biol Med 1996; 69: 477±82. Agents Chemother 2001; 45: 1295±7. 32. Binder D, Zbinden R, Widmer U, Opravil M, Krause M. Native and 48. Wuest J, Lanzendoerfer H, von Graevenitz A, Gloor HJ, Schmid B. prosthetic valve endocarditis causede by Rothia dentocariosa: diagnostic and Peritonitis caused by Actinomadura madurae in a patient on CAPD. Eur J Clin therapeutic considerations. Infection 1997; 25: 22±9. Microbiol Infect Dis 1990; 9: 700±1. 33. Spangler SK, Jacobs MR, Appelbaum PC. Susceptibility of anaerobic 49. Verville TD, Huycke MM, Greenfield LA, Fine DP, Kuhls TL, Slater LN. bacteria to trovafloxacin: comparison with other quinolones and non- Rhodococcus equi infection of humans: 12 cases and a review of the literature. quinolone antibiotics. Infect Dis Clin Pract 1996; 5 (S3): 101±3. Medicine 1994; 73: 119±32. 34. Amrikachi M, Krishnan B, Finch CJ, Shahab I. Actinomyces and Actinobacillus 50. Hsueh P-R, Hung C-C, Teng L-J, Yu M-C, Chen Y-C, Wang H-K, Luh actinomycetemcomitans-Actinomyces-associated lymphadenopathy mimicking K-T. Report of invasive Rhodococcus equi infections in Taiwan, with an lymphoma. Arch Pathol Laboratorymed 2000; 124: 1502±5. emphasis on the emergence of multidrug-resistant strains. Clin Infect Dis 35. Catlin BW. Gardnerella vaginalis. Characteristics, clinical considerations, and 1998; 27: 370±5. controversies. Clin Microbiol Rev 1992; 5: 213±37. 51. McNeil MM, Brown JM. Distribution and antimicrobial susceptibility of 36. Griffith JK, Daly JS, Dodge RA. Two cases of endocarditis due to Rhodococus equi from clinical specimens. Eur J Epidemiol 1992; 8: 437±43. Lactobacillus species: antimicrobial susceptibility, review, and discussion of 52. Bowersock TL, Salmon SA, Portis ES et al MI MICs of oxazolidinones for therapy. Clin Infect Dis 1992; 15: 250±5. Rhodococcus equi strains isolated from humans and animals. Antimicrob Agents 37. Felten A, Barreau C, Bizet C, Lagrange PH, Philippon A. Lactobacillus Chemother 2000; 44: 1367±9.

# 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 7 (Suppl. 4), 43±46