TABLE 1

Survey of intracellular antimicrobial activity against L. pneumophila by class and/or target

ClassCompound(s) by activity level (no. of times tested)a
StrongModerateWeakDetectableInactive
QuinoloneClinafloxacin,*ciprofloxacin (4),* enoxacin (3),* enrofloxacin (3),* fleroxacin,* flumequine (3),* gatifloxacin (4),* gemifloxacin (2),* levofloxacin (4),* lomefloxacin (5),* moxifloxacin (3),* nadifloxacin (2),* nalidixic acid,*# norfloxacin (4),* ofloxacin (5),* oxolinic acid (4),* pazufloxacin (2),*# pefloxacin (4),* prulifloxacin (3),* sarafloxacin (3),* sparfloxacin,* tosufloxacin (2),* trovafloxacin*Orbifloxacin, nalidixic acid#Cinoxacin (4), clinafloxacin, cloxyquin (2), difloxacin, nalidixic acid,# pazufloxacin,# pipemidic acid (2), piromidic acid (2), prulifloxacin
MacrolideAzithromycin (5),* clarithromycin (4),* erythromycin(EryPed),*# kitasamycin,* roxithromycin (4),* telithromycin (2),* josamycin (2)*Methacycline,# troleandomycin,# tylosin (3)Erythromycin ethyl succinate#Erythromycin,# troleandomycin#Desmethyl azithromycin, dirithromycin (3), erythromycin (6),# oleandomycin (3), spiramycin (3), methacycline (2),# tilmicosin, troleandomycin (2)#
TetracyclineMinocycline (5),* doxycycline (5),*# demeclocycline (2),# oxytetracycline (3)#Demeclocycline (2),# methacycline,# oxytetracycline (4)#Doxycycline,# tetracycline#Meclocycline (2),# tetracycline,# oxytetracycline (3)#Chlortetracycline (3), demeclocycline,# lymecycline, meclocycline,# methacycline (2),# rolitetracycline (2), tetracycline (3),# tigecyclined
AminoglycosideAmikacin#Apramycin,# gentamicin#Amikacin (2),# apramycin (3),# bekanamycin (2), dihydrostreptomycin (3), dibekacin, gentamicin (3),# kanamycin (3), kasugamycin (2), neomycin (4), netilmicin, paromomycin (4), ribostamycin (2), sisomicin (3), spectinomycin (5), streptomycin (4),b dihydrostreptomycin (3),b tobramycin (3)
Folate inhibitorOrmetoprim, sulfadimethoxine,# sulfamonomethoxine,# sulfaphenazole#Sulfachloropyridazine (2),# sulfadiazine (2),# sulfadimethoxine (3),# sulfadoxine (2),# sulfamerazine (2),# sulfameter (2),# sulfamethazine,# sulfamethizole (3), sulfamethoxazole (3), sulfamethoxypyridazine (2),# sulfamonomethoxine (2),# sulfaphenazole (2),# sulfaquinoxaline sodium (2), sulfathiazole (3), sulfisoxazole (2),# trimethoprim (5)cAcedapsone, dapsone (3), mafenide (3), succinylsulfathiazole (3), sulfabenzamide (3), sulfacarbamide, sulfacetamide (4), sulfachloropyridazine,# sulfadiazine (2),# sulfadoxine (2),# sulfaguanidine (3), sulfamerazine (1),# sulfameter,# sulfamethazine (2),# sulfamethoxypyridazine (1),# sulfanilamide (3), sulfanilate (1), sulfanitran (2), sulfapyridine (3), sulfisoxazole (2)#
RNA polymerase inhibitorActinomycin D, rifabutin (3),* rifampin (5),* rifamycin sv*, rifapentine (2),* rifaximin (2)*
PenicillinAmoxicillin (4), ampicillin (5), azlocillin (3), bacampicillin (2), benzylpenicillin (2), benzathine penicillin, carbenicillin (2), cloxacillin (3), dicloxacillin (4), 6-(2-ethoxy-1-naphthamido)-penicillin, flucloxacillin, hetacillin (2), amdinocillin, metampicillin (2), methacillin (2), moxalactam (2), nafcillin (3), oxacillin (3), penicillin G (Pfizerpen) (2), penicillin V (4), phenethicillin (2), piperacillin (5), pivampicillin, pivmecillinam, talampicillin, ticarcillin (2)
CephalosporinCefoperazone,# cefotaxime,# cefoxitin,# ceftazidime,# ceftriaxone (2)#Cefaclor (3), cefadroxil (3), cefalonium, cefamandole (4), cefatrizine, cefazolin (4), cefdinir (2), cefditoren (2), cefepime (2), cefixime (2), cefmenoxime, cefmetazole (4), cefonicid, cefoperazone (3),# ceforanide, cefotaxime (5),# cefotetan, cefotiam, cefoxitin (2),# cefpiramide, cefpodoxime (2), cefprozil (2), cefsulodin (3), ceftazidime (2),# ceftibuten (2), ceftiofur, ceftriaxone (2),# cefuroxime (5), cephalexin (4), cephaloridine, cephalosporanic acid, cephalosporin c (2), cephalothin (4), cephapirin (2), cepharanthine, cephradine (3)
MonobactamAztreonam (3)
CarbapenemImipenem (3), meropenem (3)
β-Lactamase inhibitorSulbactam, tazobactam
RibosomeChloramphenicol (8),* florfenicol (3),* fusidic acid (2),*# thiostrepton#Fusidic acid (2)#Clindamycin (2),# linezolid#, thiostrepton#Linezolid (2),# thiamphenicol (2)#Lincomycin (3), clindamycin (3),# thiamphenicol#
Tb specific4′- Aminosalicylic acid, phenyl aminosalicylate, capreomycin (2), clofazimine (3), cycloserine (6), ethambutol (4), ethionamide (3), isoniazid (5), prothionamide (2), pyrazinamide (5), thiolactomycin
Antimicrobial peptide, ionophoreAlamethicin,e colistin (4)e, gramicidin,e monensin (2),#,e polymyxin B (2)e
AnticancerMitomycin C (4)*Doxorubicin (3),# daunorubicin (2),# fluorouracil (5)Bleomycin (2), doxorubicin (2),# daunorubicin (2),# epirubicinDaunorubicin (2),# doxorubicin (3)#
Antiviral with known antibacterial activityfAZT (5), gemcitabine (2)
OtherCarbadox,# triclosan (2),# hinokitiolMupirocin, novobiocin,# triclosan (2)#Carbadox,# chloroxine,# decoyinine, nitrofurantoin (2),# novobiocin#Carbadox,# furazolidone,# nitrofurantoin,# novobiocin,# vancomycin#Actinonin, bacitracin (3), chlorhexidine,# chloroxine (2),# chloroxylenol (2), daptomycin (3), fosfomycin (3), furazolidone (2),# ikarugamycin,e lasalocid (2), metronidazole (4), nifuroxazide, nifursol, nifurtimox, nitrofurantoin,# nitrofurazone (2), monensin (2),# novobiocin,# ornidazole (2), ramoplanin, teicoplanin, tinidazole (4), vancomycin (3),# viomycin
  • a Numbers in parentheses indicate the number of times compounds were represented and tested in bioactive libraries. Activity is defined as follows: inactive, no significant reduction in luminescence (z score of <3) (10); detectable, <4-fold reduction in luminescence (z score of >3); weak, ≥4-fold reduction in luminescence; moderate, ≥16-fold and <64-fold reduction in luminescence; strong, ≥64 fold reduction in luminescence. Very strong activity (≥256-fold reduction up to complete suppression of luminescence) is indicated by an asterisk (*). The number sign (#) indicates disparate fold reduction values between replicates of the same compound from different libraries. Therefore, antimicrobials are listed in multiple categories. When replicates fall on either side of strong and very strong activity, the designation represents the average fold reduction for all examples of the indicated compound. AZT, zidovudine.

  • b Screening strain has an rpsL mutation and is inherently streptomycin resistant.

  • c Screening strain has a thyA mutation and is inherently trimethoprim resistant.

  • d Tigecycline is subject to oxidative inactivation. Negative screening results are therefore unreliable, as confirmed during the follow-up analysis summarized in Table 2 with freshly made antibiotic solution.

  • e Inactive and/or host cell toxic.

  • f See references 52 to 57.