TABLE 3.
Rifampin combination antimicrobial in vitro and in vivo studiesa
| Subject and author(s) (reference) | Combined antibiotic(s) | Organism(s) |
In vitro |
In vivo |
||||
|---|---|---|---|---|---|---|---|---|
| Method | Interaction | Outcome | Animal | Infection | Outcome | |||
| Antistaphylococcal penicillins | ||||||||
| Sande and Johnson (219) | Penicillin | MSSA | Rabbit | Endocarditis | Rifampin resistance emerged | |||
| Zinner et al. (281) | Methicillin-oxacillin | MSSA/MRSA | TK/CB SBA | A, S | A at high-dose oxacillin, S at low-dose oxacillin | |||
| Watanakunakorn and Tisone (262) | Nafcillin, oxacillin | MSSA | TK | A, I | No S seen | |||
| Maduri et al. (160) | Oxacillin | MSSA, MRSA | CB, TK, SBA | A, I | Most isolates A; at low doses, S or I | |||
| Hackbarth et al. (112) | Nafillin | MSSA | SBA | A | Reduced activity | |||
| Cehpalosporins | ||||||||
| Zinner et al. (281) | Cephalothin | MSSA/MRSA | TK/CB SBA | A | No benefit | |||
| Norden (185) | Cephalothin | MSSA | Rabbits | Osteomyelitis | Rifampin resistance emerged; other antibiotics sensitive | |||
| Brandt et al. (37) | Cefazolin | MSSA | Rabbit | Endocarditis | Antagonism with concentrations above MIC | |||
| Brandt et al. (36) | Cefazolin, cefpirome | CoNS | Rabbit | Endocarditis | Not predictive; better than monotherapy | |||
| Cormican et al. (56) | Cefotaxime | PRSP | Rabbit | CSF | Reduced activity with | |||
| Gordon et al. (107) | Cefotaxime, ceftazidime, cefuroxime, ceftriaxone | Haemophilus influenzae | TK | S | Greater than MIC | combination | ||
| Ribes et al. (211) | Ceftriaxone | PRSP | TK | A | When subinhibitory | Rabbit | Meningitis | Improved efficacy when combined |
| Suntur et al. (236) | Ceftriaxone | PRSP | concentrations used; resistance to rifampin | Rabbit | Meningitis | Combination as good as ceftriaxone and vancomycin | ||
| Valdes (248) | Cefpirome, ceftazadime | Pseudomonas | FIC agar dilution | S | Bactericidal effect greater when given early in incubation | |||
| Vancomycin | ||||||||
| Bayer and Morrison (26) | Vancomycin | MRSA, MSSA | TK, CB | I or S, TK; A, CB | Most I by TK; S late phenomenon; all A | |||
| Bayer and Lam (25) | Vancomycin | MRSA | by CB | Rabbit | Endocarditis | No evidence of antagonism | ||
| Lowy et al. (158) | Vancomycin and gentamicin | CoNS | TK | S | Rifampin-resistant strains when used with vancomycin | |||
| Tuazon et al. (246) | Vancomycin | MSSA | MBC | I, S | 5/20 synergistic | |||
| Van der Auwera and Joly (251) | Vancomycin | MSSA, MRSA | MBC | S | Variable results | |||
| Watanakunacorn and Guerriero (261) | Vancomycin | MSSA | TK | A | 43 of 50 antagonistic | |||
| Stein and Libertin (232) | Vancomycin | Nutritionally variant streptococci | TK | S | ||||
| Norden and Shaffer (187) | Vancomycin | MSSA | Rabbits | Osteomyelitis | 85% effective sensitive | |||
| Quinolones | ||||||||
| Hessen et al. (119) | Temfloxacin | MRSA | Rabbit | Endocarditis | Significant reduction in bacterial counts | |||
| Dworkin et al. (73) | Ciprofloxacin, perfloxacin | MRSA | Rat | Osteomyelitis | Combinations better than monotherapy | |||
| Kaatz et al. (137) | Ciprofloxacin | MSSA | Rabbit | Endocarditis | Unpredictable, but combination had fewer resistant isolates emerge | |||
| Henry (117) | Ciprofloxacin | MRSA | Rats | Osteomyelitis | Most effective; rifampin resistance | |||
| Baltch et al. (18) | Levofloxacin | Legionella pneumophila | TK | S | Only antibiotic of | in vancomycin group | ||
| Havlichek (114) | Ciprofloxacin | Legionella pneumophila | group | Guinea pigs | Intraperitoneal | No advantage over monotherapy | ||
| Linezolid | ||||||||
| Baldoni et al. (16) | Linezolid | MRSA | Guinea pigs | Foreign body | Improved killing combined | |||
| Grohs et al. (110) | Linezolid | MRSA | TK | I | ||||
| Jacqueline et al. (128) | Linezolid | MRSA | TK | A | Most active | |||
| Tsaganos et al. (243) | Linezolid | MRSA | Rabbit | Endocarditis | Increased cidality in lungs | |||
| Dailey et al. (62) | Linezolid | MRSA | Rabbit | Endocarditis | Indifference | |||
| Daptomycin | ||||||||
| Credito et al. (59) | Daptomycin, gentamicin | MRSA, hVISA | TK | S | All isolates | |||
| Khasawneh et al. (143) | Daptomycin | MRSA | TK | I, A | No benefit if rifampin resistant initially | |||
| Sakoulos et al. (217) | Daptomycin | MRSA | Rats | Endocarditis | Combination statistically better | |||
| Rand (208) | Daptomycin | VRE | Etest MICs | I | No benefit with novel method | than daptomycin alone | ||
| Pankey (191) | Daptomycin | VRE | TK, Etest | S, I | 75% isolates synergistic | |||
| Other antimicrobials | ||||||||
| Zinner et al. (281) | Minocycline | MSSA | CB | S | In vitro synergy | |||
| Segreti et al. (224) | Minocycline | MSSA, MRSA, CoNS | MBC | I, S | About 30% synergy | |||
| Hackbarth et al. (112) | Erythromycin, clindamycin, trimethoprim | MSSA | SBA | S | Resistance emerges with trimethoprim | |||
| Watanakunakorn (260) | Clindamycin | MSSA | TK | S, I | Only for clindamycin-sensitive strains | |||
| Harvey (113) | Trimethoprim | Klebsiella, Enterococcus faecalis | TK | A | ||||
| Zarrouk et al. (273) | Quinupristin-dalfopristin | MSSA | TK | I | Rifampin resistance emerged | Rabbit | Endocarditis | Highly synergistic compared to in vitro |
a
Abbreviations: TK, time-kill; CB, checkerboard; SBA, serum bactericidal activity; FIC, fractional inhibitory concentration; MBC, minimal bactericidal concentration; S, synergy; A, antagonism; I, indeterminate (additive); MSSA, methicillin-sensitive Staphylococcus aureus; MRSA, methicillin-resistant S. aureus; hVISA, heteroresistant vancomycin-intermediate S. aureus; CoNS, coagulase-negative staphylococci; PSSP, penicillin-sensitive Streptococcus pneumoniae; PRSP, penicillin-resistant S. pneumoniae; VRE, vancomycin-resistant enterococci.