马红球菌-抗生素治疗

Patricia Muñoz MD, PhD

Pablo Martín Rabadán MD

Emilio Bouza MD, PhD 

Division of Clinical Microbiology and Infectious Diseases

Hospital General Universitario "Gregorio Marañón"

Universidad Complutense. Madrid. Spain

Address correspondence and reprint requests to :

Patricia Muñoz. MD

Servicio de Microbiología Clínica y E. Infecciosas-VIH.

Hospital General Universitario "Gregorio Marañón".

Doctor Esquerdo 46. 28007 Madrid. Spain.

Phone:34-91-58684 53 ;  Fax:34-91-5044906.

email: pmunoz@micro.hggm.es

译者：张峣 主治医师

            北京协和医院 感染科

            Email：zhangyao1@gmail.com

GENERAL DESCRIPTION 

               Rhodococcus equi infections have increased in the last years, mainly in immunocompromised patients (33, 85). Although they are particularly frequent in HIV infected patients (60, 112), they have also been described in hematological patients (2, 4, 21, 24, 30, 87, 95, 134, 135), patients with renal failure (20, 142), alcoholism (81), lung cancer (146), rheumatoid arthritis (88, 140), sarcoidosis (62), in transplant recipients (100) and even in previously healthy patients (42, 73).  

               The most common way of infection is the airborne route (112), although it can also be acquired orally or by direct inoculation (85, 141). Dissemination from an initial site (usually the lung) has been found to be the origin of abscesses throughout the body (CNS, skin, paraspinal, bone, kidney, etc) (106, 119, 127).  

               Diagnosis may be difficult to establish for Microbiological laboratories, and the awareness of possible mistakes in the recognition of this pathogen will contribute to a more frequent report of cases (85). Rhodococcus equi is an intracellular microorganism and its eradication requires long-term combined antimicrobial therapy and sometimes, surgical excision (33). Finally, the recent introduction of highly efficacious antiretroviral therapy in HIV positive patients (HAART) is clearly contributing to the reduction of the incidence of this infection (125).  

Microbiology Guided Medline Search 

               Confirmation of infection can only be made by isolating the microorganism from clinical samples. Rhodococcus (red coccus) equi is an aerobic pleomorphic saprophyte coccobacillus that grows as mucoid, salmon-pink, colonies within 24 to 72 hours. If cultured in non-selective media, the microorganism may be overlooked or regarded as a non-pathogenic "diphtheroid" or as a saprophytic coccus (90). The use of selective culture plates such as colistine-nalidixic agar (CNA), phenyl-ethanol agar (PEA), NANAT agar or Ceftazidime-novobiocin agar, incubated aerobically at 37ºC for up to seven days may facilitate the isolation of R. equi in contaminated samples (148, 152, 154).  

               In addition, R. equi may be mistaken as Mycobacterium species due to its partially acid-fast nature, especially on clinical samples. It can be distinguished from some mycobacterial species by the 14-day arylsulfatase test, as Rhodococcus is negative for this reaction. For all the above-mentioned reasons, the real incidence of the disease may be underestimated (56, 85, 112, 127).  

               Regarding the susceptibility tests, the microdilution method, the disk diffusion test and the E test can provide useful results as far as the inoculum is standardized (143). However, no standard breakpoints are available.  

Epidemiology Guided Medline Search 

                R. equi is a widespread organism in soil and in herbivore manure (12, 54). It is a well-known cause of lung infection in foals, and also causes submandibular adenitis in swine. Infections in other animals including calves, sheep, goats, dogs and cats have been described. In humans the route of infection is thought to be inhalation or ingestion of the microorganisms. The exposure to farm dust, animals or manure can be elicited in less than one half to up to two thirds of cases (9, 42, 49, 60, 73, 112, 127, 146), and it is less common in HIV positive patients (45% vs. 20%) (60). In 6 out of 24 cases pneumonia was acquired by HIV patients who shared room with R. equi infected patients, raising the concern of human-to-human transmission (9). Traumatic inoculation or superinfection of wounds can also lead to infection (145).

               The first human case was reported in 1967 in a patient receiving high dose corticosteroids (53). The first cases of R. equi pneumonia in HIV-infected patients were reported in 1986 and 87 (88, 121). Between 1967 and 1996, 115 cases of infection caused by R. equi have been published (39, 40, 60, 104) and 63 more since then (1-3, 5, 10, 11, 16, 19, 22, 23, 25, 29, 37, 41, 44, 46, 49, 55-57, 59, 61, 66, 67, 73, 75-80, 84, 87, 89, 91-93, 97, 99-102, 108, 120, 123, 124, 128, 130-132, 136, 138, 141, 144, 145, 147).  

               In a review of 72 cases in humans, published in 1991, 86% of the patients were immunocompromised with half of those occurring in patients infected by HIV (146). More recently, a review of 72 cases in HIV positive patients was published (23). Therefore, at present the total number of R. equi human infections described is roughly around two hundred cases.  

Clinical Manifestations Guided Medline Search 

               Pneumonia is the most common manifestation of R. equi infection in immunocompromised patients (23, 33, 112, 146). More than 80% of reported patients had fever and cough as presenting symptoms. Pleuritic chest pain and hemoptysis was reported in approximately 35 and 15% respectively (23). R. equi bacteremia was found in approximately one half of HIV infected patients (9, 146). Complications include the development of pleural effusion (81), endobronchial lesions (129), a pseudotumoral presentation (15, 36), cardiac tamponade (82), pneumothorax (146) or mediastinitis (25).  

               Clinical experience and animal models have shown that clearance of R. equi is impaired in the immunocompromised host and relapses are common despite maintenance antibiotic therapy. Before HAART was available, relapses of pneumonia were described in up to 82% of cases of HIV infected patients (9). There is no published experience on the evolution of R. equi infections in HIV + patients after immune-restoration; our personal impression is that we are witnessing a sharp decrease in the incidence of R. equi infection in this particular population. 

               Extra pulmonary disease, especially organ abscesses, has been also reported. They may be diagnosed with the initial pneumonia or during the relapses. Central nervous system abscess is the most common extra pulmonary presentation of relapsing infection (146), this complication seems especially frequent in patients with multiple relapses. In nearly all reported cases there was a concomitant or previous lung infection due to this organism (9, 47, 59, 82, 107, 108, 133, 146). Pericarditis (82), meningitis (110), mastoiditis (67, 75, 86), abscesses in the liver (82), spleen (14), kidney (133), thyroid (93), iliopsoas muscle (45), bone (46, 106) subcutaneous tissue (9), foot mycetoma (8) and adenitis (29, 45) have been observed in HIV positive patients. 

               Intestinal involvement is known to occur in horses and it has been reported in an HIV + patient with disseminated R. equi infection and chronic diarrhea; patient’s colonoscopy revealed multiple polipoid inflammatory lesions infiltrated with R. equi (59, 141). Co-infection by R. equi and other pathogens have been occasionally found (45). 

               The chest X rays in 102 cases of lung infection (9, 23) revealed cavities (usually single) in 73 cases, consolidation or infiltrates in 34 cases, and pleural effusions in 11. Some patients have more than one type of lesion and in some cases an interstitial pattern preceded the development of consolidation or cavity formation. In a series of 78 cases of lung cavitation identified in 73 HIV + patients, R. equi was responsible of 6 out of 69 cases (8.6%) with microbiological results, after Mycobacterium tuberculosis, Pneumocystis carinii, Pseudomonas aeruginosa, and Staphylococcus aureus (116). If patients with CD4 count above 200 and the intravenous drug users with cavitating pneumonia secondary to endocarditis were excluded from this series, R. equi accounted for approximately 10% of cases of cavitary pneumonia. Cavities usually have thick walls and sometimes an air-fluid level may be identified (151). Other presentations include mediastinal enlargement, or pulmonary nodules (151).  

               CT scan is recommended in most patients with R. equi pneumonia to better define the extension of the disease.  

Laboratory Diagnosis Guided Medline Search

               The efficacy of sputum samples for establishing the etiological diagnosis relies on the quality of the sample (40, 41, 149) and it is usually higher in HIV positive patients. Invasive techniques may be needed (33). Blood cultures are positive in a large proportion of HIV positive patients, in a third of HIV negative patients and in 25% of solid organ recipients (40, 60, 149). Other useful samples include pleural, peritoneal or articular fluids, abscess aspirations, skin or soft tissue biopsies, lymph nodes, feces, urine or autopsy samples (60, 96, 112). 

               Histology usually reveals a necrotizing granulomatous reaction with macrophages, neutrophils, and intracellular gram-positive organisms. Malakoplakia (sometimes spelled as malacoplakia) is an unusual inflammatory condition that usually affects the lower urinary tract and is associated with an impaired processing of microorganisms within histiocytes. Histopathologically it is characterized by accumulations of benign macrophages associated with diagnostic intracellular and extracellular calcospherites, termed Michaelis-Gutmann bodies. Lung malakoplakia is an especially rare condition with only 24 reported cases included in a 1997 review. Eighteen out of this 24 had R. equi pneumonia and 14 out of 15 were HIV positive (79). The diagnosis can be determined on biopsies, bronchial washes, bronchial aspirates or brush cytology specimens. This disease should be considered when a R. equi pneumonia persists after several months of antibiotic treatment.  

Pathogenesis Guided Medline Search 

                R. equi is a facultative intracellular pathogen that infects macrophages and survives inside the lysosomes. It has a complex cell wall which contains glucosamine, muramic acid, glutamic acid and alanine (like that of Nocardia and Mycobacterium), is thought to prevent phagosome-lysosome fusion, resist the oxidative burst and cause a nonspecific degranulation of lysosomes, thereby allowing intra-histiocytic survival and chronic infection. Cortisone and cyclophosphamide impair the pulmonary clearance of R. equi (18).    

SUSCEPTIBILITY IN VITRO AND IN VIVO Guided Medline Search In Vitro and In Vivo

               Due to the low incidence of this disease no comparative studies on antimicrobial treatment have been conducted. Present day therapeutic recommendations are based on expert opinions guided by in vitro susceptibility tests, pharmacodynamic and pharmacokinetic considerations, clinical experience on animals, experimental infection models, and rather anecdotal clinical experience in humans.  

Single Drug

               There is neither consensus nor NCCLS guidelines on the antibiotic breakpoints to be used with Rhodococcus spp isolates. The information available is based on very few number of isolates (Table 1), different laboratory procedures and different personal interpretations (9, 32, 65).

               Overall, similar susceptibility patterns have been found both in human and animal isolates. The interpretation of those results must take in account not only the concentration that the antimicrobials reach in serum but its penetration into the lysosomes, and the antimicrobial activity at the low pH and PO₂ conditions present in this ecological niche. Furthermore, it is not clear if the intra-lysosomal survival mechanisms of Rhodococcus, in the absence of an adequate immune response, significantly modify the activity of the antimicrobials accessing the site. 

               In a recent study performed by the CDC with 107 strains, recovered during a 17-year period, 50% of the isolates were resistant to b-lactams and clindamycin (96). Vancomycin, imipenem, erythromycin, rifampin, tetracyclines and cotrimoxazole showed an excellent in vitro activity (less than 5% resistance rate) and ciprofloxacin showed 16% of resistance. The authors found different results within different antimicrobials of the same family, so results should not be extrapolated to non-tested drugs (105). The in vitro activity of teicoplanin, meropenem and the aminoglycosides is very good (70, 72, 103). Linezolid, a new oxazolidinone antimicrobial, showed an MIC₉₀ of 2,0 mg/mL (17). The only bactericidal drugs against R. equi were the glycopeptides, aminoglycosides, sparfloxacin, and ciprofloxacin, although this has not been confirmed in other studies (105).  

Combination Drugs 

               As determined by fractional inhibitory concentration indices, four combinations were synergistic: rifampin-erythromycin, rifampin-minocycline, erythromycin-minocycline and imipenem-amikacin. However, no antibiotic combinations were synergistic with the time-kill kinetic method in one study (105). In another report, using time-kill studies of a single strain, an additive effect was observed between rifampin plus imipenem or azithromycin. Indifference was observed for the combination of vancomycin and rifampin. In vitro antagonism was demonstrated with the combination of levofloxacin and rifampin (77). In this same study, antagonism was observed with levofloxacin and azithromycin independent of the dose of levofloxacin used. There was no apparent difference in the killing rate between levofloxacin at 1 g once/day or 500 mg once/day dose. The combination of gentamicin with rifampin or erythromycin has been found antagonistic by other authors (113, 146).  

               Studies with other bacterial genus have frequently demonstrated in vitro antagonism between clindamycin and erythromycin, probably as result of competition for the target site in the bacterial ribosome. The combination of macrolides and aminoglycosides have been found useful probably due to the fact that aminoglycosides act against the extracellular compartment and macrolides against the intracellular one (48).  

Animal Studies: Animal models may be more accurate than in-vitro data to analyze antimicrobial activity of single drugs and combination therapy against Rhodococcus isolates. A nude mice model of R. equi infection was established to compare the antimicrobial activity of amikacin, ciprofloxacin, erythromycin, imipenem, minocycline, rifampin and vancomycin, alone and in combination (103). Therapy was started 4 days after animals had being challenged with an intravenous suspension of one strain of R. equi. The end point of the study was the reduction in bacterial load in lung and spleen tissues after 4 or 11 days of treatment. Untreated controls were unable to clear the infection. Vancomycin, imipenem, and rifampin were the most effective agents as single therapy, while amikacin, ciprofloxacin, erythromycin, and minocycline alone were not active. The most active therapies (in descending order) were vancomycin plus rifampin, vancomycin plus imipenem, vancomycin, amikacin plus imipenem, imipenem, rifampin plus erythromycin and rifampin plus minocycline. Imipenem-resistant and amikacin-resistant mutants were detected during the treatment and also in the untreated control group. In this animal model R. equi eradication was not analyzed as an endpoint. The high activity of vancomycin may have been enhanced by the presence of a high number of extracellular bacteria.  

Veterinary Clinical Experience: The combination of erythromycin (25 mg/kg three times daily) and rifampin (5 mg/kg twice daily) has been used on foals since 1981 and has been considered the therapy of choice since then (63, 114). The selection was made because both drugs are lipid-soluble antibiotics capable of intracellular penetration with synergistic activity. The success of this therapy in foals has been analyzed in non-randomized studies. In a review of R. equi pneumonia in foals 20 out of 48 foals survived and 28 died or were euthanized. Thirteen of the 20 surviving foals were treated with erythromycin and/or rifampin. A decline in mortality rate was observed with the introduction of the combination of erythromycin and rifampin. None of the 17 foals treated with penicillin and gentamicin survived (137).   

ANTIMICROBIAL THERAPY Smart search

Drug of Choice Guided Medline Search

药物选择

               Probably due to the absence of clear therapeutical guidelines, virtually every imaginable combination has been used (Table 2 and 3). Monotherapy was ineffective in a number of cases and is not recommended. Combinations of two or three antimicrobial agents have been usually prescribed.

        由于目前缺乏明确的治疗规范，多数可能的组合都在以往有过使用（表2和3）。单药治疗对于有些病例效果不佳，不被推荐。常规的治疗是两种或三种抗生素联合使用。  

               The use of bactericidal drugs with extracellular activity (to reduce the bacterial load) followed by or in combination with drugs with intracellular activity such as erythromycin, rifampin, or ciprofloxacin has been proposed. As the central nervous system is a frequent secondary site of infection the use of drugs that reach the CNS seems advisable (146).

        建议使用有细胞外活性的杀菌药（降低菌量），并结合或续贯使用有细胞内活性的药物，如红霉素，利福平或环丙沙星。由于中枢神经系统是常见的继发感染部位，使用对血脑屏障通透性高的药物可能效果更好。 

               Initial therapy must usually deal with a high bacterial load and frequent bacteremia, so the combination of at least two parenteral drugs with bactericidal activity is recommended. In immunocompromised patients it should include vancomycin or teicoplanin, probably in combination with imipenem (31, 33, 117). The addition of an aminoglycoside may be considered in severe cases. This parenteral therapy should be maintained during at least three weeks (33).

        初治时，由于菌量较大和菌血症常见，建议至少要联合使用两种肠外剂型的杀菌药物。对于免疫功能低下的患者，应使用万古霉素和替考拉宁，并考虑联合使用亚胺培南。重症病例可以考虑添加氨基糖苷类药物，并至少要使用3周。 

               After initial recovery (2-4 weeks), drugs with good intracellular penetration and with oral absorption are warranted and combinations including macrolides and rifampin are preferred (31, 146). Arlotti et al., recommend erythromycin plus rifampin as first choice therapy at this stage, with alternatives such as erythromycin plus ciprofloxacin, or rifampin plus ciprofloxacin (9). Azithromycin is also a promising combination due to its high tissue levels (58, 64, 69). Oral therapy should be administered for at least two months. Excision of infected tissue may be considered for refractory cases.

        2-4周的初始治疗后，推荐选用胞内浓度高和口服吸收好的组合，如包括大环内酯和利福平的组合。Arlotti等建议在此阶段首选红霉素加利福平的组合，其它方案包括红霉素加环丙沙星，或利福平加环丙沙星。阿奇霉素有较高的组织浓度，应用前景也很广阔。口服药物治疗至少应维持两个月。对于顽固性病例需要考虑切除感染灶。  

               For long-term suppressive therapy a macrolide plus rifampin is generally recommended. An effective alternative to rifampin can be a quinolone or doxycycline.

        长期治疗病例通常推荐使用大环内酯类加利福平疗法。利福平的有效替代药物可以是喹诺酮类或强力霉素（多西环素）。 

               Serial cultures of respiratory samples and feces to detect R. equi may be used to document persistence of infection and development of resistance. If possible, correction of underlying risk factors is warranted (112).

        呼吸道样本和粪便经过一系列的培养可能会检测到马红球菌，检测到马红球菌证明存在继发性感染和耐药。如果条件允许的话，纠正潜在的危险因素也是必要的。  

Special Infection Guided Medline Search

特殊感染

               Very few cases of Rhodococcus equi meningitis have been described (38, 94, 110, 128, 145). Of the four cases, reviewed by DeMarais et al, only one was a patient with AIDS, and the remaining 3 did not have an underlying immunodeficiency. One patient who developed meningitis after head trauma and shunt placement was unsuccessfully treated with vancomycin and rifampin, and finally responded to levofloxacin (500 mg iv twice a day) and shunt removal. (128). 

        有关马红球菌脑膜炎病例的报道极少。DeMarais等报道的4名病例中，只有1名病例合并艾滋病，其余3名病例均没有基础免疫缺陷。一个病人因头部外伤后行脑脊液分流而感染脑膜炎，使用万古霉素和利福平后未见好转，后改用左氧氟沙星（500毫克静脉注射，一天2次）病情改善、分流移除。 

               No cases of endocarditis have been described.

        尚无心内膜炎病例报道。  

Underlying Diseases

基础疾病

               Outcome is related to host immune status and adherence to therapy. Infections are typically cured in immunocompetent hosts in contrast to relapses and chronic disease seen in the immunocompromised, especially in the first few weeks after discontinuation of suppressive therapy.

        疾病结局与患者的免疫状态和对治疗的依从性有关。相对于免疫功能受损的患者，复和慢性化常见，特别是在停药的前几周，而在免疫功能正常的宿主通常可以治愈。  

               Published prognostic data is available for AIDS patients, prior to the advent of potent anti-retroviral therapy. In a series of 12 cases, complete recovery (clinical, radiological and microbiological) was observed in 2/12 patients and clinical response (resolution of the signs reported on presentation) in 9/12 cases; the remaining case died within 2 weeks, without signs of improvement. The overall mortality was 58 %, with a mean survival time of 5.75 months (range 0-17 months) (40). In a series of 22 AIDS patients with follow-up data, the mean survival time was 11.4 months (range 2-24). R equi infection was considered the main cause of death in 7 of 20 fatal cases (9).

        有研究报道抗逆转录病毒疗法之前艾滋病患者的预后。12名病例中，有2名痊愈（临床，影像学和微生物学），9名有临床改善（与就诊时的情况相比），其余病例均在2周内死亡。这群患者总的死亡率为58%，平均存活时间为5.75个月（0-17个月）。另22名艾滋病患者的随访资料显示，其平均生存时间为11.4个月（2-24月），20名死亡病例中有7例被认为死于马红球菌感染。 

               In HIV positive patients, oral suppressive therapy may need to be continued for life, or at least until immune-restoration. (60, 146). However, since the advent of HAART, an impressive improvement in the prognosis of opportunistic infections has been observed in this population and will probably make unnecessary the administration of chronic suppressive therapy (5, 125).

        对于艾滋病患者中的马红球菌感染，可能需要终身口服药物治疗，或者至少需要服用到免疫功能明显恢复。总体上，高效抗逆转录病毒疗法的出现明显地改善了机会性感染的预后，也减少的长期治疗的使用。 

               Regarding interactions, the use of rifampin is not recommended in patients receiving protease inhibitors in whom rifabutin (at half dose) is preferred. In the case of solid organ transplant recipients on cyclosporine A, rifampin should be avoided due to the risk of inducing allograft rejection due to subtherapeutic serum levels of cyclosporine A.  Interaction between rifampin and methadone has also been described. Aminoglycosides should be used with precaution due to potential synergic nephrotoxicity.

        由于存在药物交互作用，接受蛋白酶抑制剂的患者不建议同时服用利福平，应首选利福布丁（半剂量）。服用环孢素A的实体器官移植受者应避免使用利福平，后者可以导致环孢素A的血药浓度不足，会产生移植排斥反应。利福平和美沙酮的交互作用也有报道。与有肾毒性的药物联合使用时，氨基糖苷类药物应慎用。  

Alternative Therapy Guided Medline Search

其他治疗方案

               Most treatment options used for human therapy are summarized in tables 2 and 3. Most of them include some of the following drugs.

        多数可选的治疗方案总结在表2和表3中，多数方案包括以下一些药物。 

               Trimethoprim-sulfamethoxazole, used as prophylaxis of Pneumocystis carinii infection, does not seem to prevent R. equi pneumonia (4, 28) and has also been found ineffective as treatment (126).

        甲氧苄啶和磺胺甲恶唑是卡氏肺孢子虫感染的治疗药物，但这两种药似乎并不能有效的预防和治疗马红球菌。 

                Development of resistance has been documented in humans and in horses after monotherapy with quinolones or rifampin or after prolonged two-drug combination therapy (31, 74, 118, 139). Low-level rifampin resistance has been found to be due to antibiotic inactivation (6).

        喹诺酮或利福平单独用药或长期联合治疗后，会发生耐药性。低水平的利福平耐药被认为与抗生素失活有关。  

               Quinolones have been included as part of the multidrug therapy, but its contribution to the patient outcome is unclear. Ciprofloxacin MICs are close to the breakpoint for susceptibility, and, although it penetrates intracellularly, it is only useful in some intracellular infections (such as legionellosis) but not in others (such as brucellosis). In one case, oral therapy failed to prevent relapse, while parenteral ciprofloxacin plus imipenem successfully controlled the infection (146). Better results may be expected from the use of newer quinolones, with increased activity against Gram positive bacteria, such as levofloxacin (77). The development of decreased susceptibility during therapy should probably be sought for.

        喹诺酮类药物常作为联合治疗的一部分，但这类药物在疗效中的贡献尚不明确。环丙沙星最小抑菌浓度接近于敏感临界值，虽然它可以渗透到细胞内，但只对一些胞内感染有效（比如军团杆菌感染），而对其他（如布鲁氏杆菌病）则可能无效。曾经有一个病例口服药物治疗后未能阻止疾病的进展，后用静脉环丙沙星加亚胺培南成功控制了感染。新的喹诺酮类药物（比如左氧氟沙星）增加了抗革兰氏阳性菌的活性，这类药物有更好的应用前景。在治疗过程中需要注意敏感性下降的问题。 

               The use of β-lactams is generally not recommended. Most authors consider that the MICs to penicillin ampicillin and cefalosporins are too high to be regarded as susceptible, and the susceptibility may decrease during therapy. In spite of this, some patients have improved with cefotaxime therapy (110). The presence of b-lactamasees has not been described in R. equi, therefore the use of a b-lactamase inhibitor such as clavulanate, sulbactam or tazobactam is not justified.

        通常不推荐使用β-内酰胺类药物。多数学者认为氨苄青霉素和头孢菌素对马红球菌的最小抑菌浓度过高，并且其敏感性在治疗过程中可能会降低。尽管如此，有些患者使用头孢噻肟治疗后，病情还是得到了缓解。尚未在马红球菌中发现β-内酰胺酶，因此无需使用β-内酰胺酶抑制剂（如克拉维酸钾、舒巴坦、三唑巴坦）。  

               Imipenem in combination with a glycopeptide was found the only bactericidal combination of various assayed. It has been recommended as first choice therapy since a dramatic clinical improvement in R. equi infected patients occurred shortly after this therapy was instituted in three anecdotal reports (28, 117, 118). Primary resistance to imipenem has been described (43), as well as the development of decreased susceptibility during treatment (31). In vitro studies have shown imipenem decreased susceptibility relates to changes in the penicillin-binding proteins (PBPs) and the association of a beta-lactam antibiotic resulted in an antagonic effect (104). Imipenem susceptibility of initial and subsequent R. equi isolates must be monitored to detect emergence of resistance and the simultaneous use of b-lactams and rifampin should probably be avoided.

        亚胺培南联合糖肽类抗生素被认为是一个有效的杀菌组合。3例散发的马红球菌感染患者使用亚胺培南联合糖肽类抗生素治疗后，临床症状得到了明显改善，此后，这个组合被推荐为的首选方案。对亚胺培南的原发耐药以及治疗过程中的敏感性降低已有报道。体外试验表明，亚胺培南敏感性的降低与青霉素结合蛋白（PBPs）的改变有关。对于最初和随后分离到的马红球菌菌株，亚胺培南的敏感性应当进行监测，同时也尽量避免使用β -内酰胺类抗生素和利福平。 

               The aminoglycosides have been successfully used in combination with bacterial wall-active antibiotics such as beta-lactams and glycopeptides in many infections including a few R. equi infections. Clindamycin has probably no place in the treatment of R. equi infections. It has failed as monotherapy and has been used with limited success in association with other antimicrobials.

        氨基糖甙类药物联合针对细菌细胞壁的抗生素（如β -内酰胺类和糖肽类）已被成功用于治疗多种感染，包括部分马红球菌感染。克林霉素可能对马红球菌无效，以往的单药治疗不成功，即使与其他抗生素联合使用时，疗效也非常有限。   

(Printable Version of Antimicrobial Therapy for Rhodococcus equi)　

ADJUNCTIVE THERAPY Guided Medline Search

               Lobectomy has been employed in a number of patients when poor clinical improvement was noted after antibiotic therapy. There is no reliable data on the usefulness of this approach but it may not greatly increase the survival (9, 60). It may be considered a therapeutic option in patients with persistent immunocompromise and pneumonia refractory to prolonged antimicrobial therapy, large abscess or inflammatory pseudotumor. Drainage of empyemas and localized abscesses has been beneficial (112, 146).    

ENDPOINTS FOR MONITORING THERAPY Guided Medline Search

               There are no clear guidelines on the duration of therapy. It probably should be individualized depending on the immunologic situation of the patient. Immunocompetent patients with R. equi pneumonia may recover completely with a short course of erythromycin while severely immunocompromised patients may relapse shortly after prolonged proper therapy is discontinued (146). As a general recommendation immunocompromised patients should receive 2 to 6 months of antibiotic therapy, or at least till cultures become negative and clinical symptoms disappear (71).   

VACCINES Guided Medline Search

               No commercial vaccines are available.   

PREVENTION OR INFECTION CONTROL MEASURES Guided Medline Search Smart search

               Rhodococcus equi may be isolated from soil, air and water. It has been recovered from schools and day-care centers (7). Although it can be considered a zoonosis, some authors recommend that considering the very low risk of transmission, pet contact should not be prohibited even to HIV infected patients (52). In the case of hematological patients, avoidance of exposure to domestic horses or their habitat during periods of aggressive chemotherapeutic administration seems reasonable, its efficacy has not been proven (134).  

               Taking into account the cases of possible person-to-person transmission described, respiratory isolation of these patients is recommended if possible (9).

Table 1. Minimal Inhibitory Concentrations (MICs) of R. equi Strains+

Table 2. Antimicrobial Therapies and Clinical Response in a Literature Review [Download PDF]

表2  文献报道的抗生素方案和疗效

Table 3. Response to Maintenance Therapy [Download PDF]

表3  维持治疗的疗效

抗生素	复发情况	参考文献
环丙沙星	无	(146)
环丙沙星	尚佳	(136)
红霉素	尚佳	(150)
红霉素 + 利福平	尚佳	(13, 43, 98, 146)
克拉霉素 + 利福平	尚佳	(13)
克拉霉素 + 利福平	无	(10)
红霉素 + 多西环素	尚佳	(36, 50)
红霉素 + 四环素 + 克林霉素	尚佳	(68)
罗红霉素 + 多西环素	尚佳	(28)
红霉素 + 米诺环素	尚佳	(118)
克拉霉素 + 环丙沙星	尚佳	(10)
克拉霉素 + 复方新诺明	尚佳	(51)
替考拉宁 + 头孢曲松	尚佳	(28)
克林霉素 +青霉素	无	(126)

REFERENCES

1. Ahmed BA, Burden P, Tang A, Naik RB.Community-acquired lobar pneumonia in an HIV-infected patient. Int J STD AIDS 1997;8:789-91. [PubMed]

2. Akan H, Akova M, Ataoglu H, Aksu G, Arslan O, Koc H. Rhodococcus equi and Nocardia brasiliensis infection of the brain and liver in a patient with acute nonlymphoblastic leukemia. Eur J Clin Microbiol Infect Dis 1998;17:737-9. [PubMed]

3. Alcalde Encinas MM, Garcia Garcia J, Martinez Madrid OJ, Garcia Henarejos JA. [Bronchial malacoplakia associated with Rhodococcus equi pneumonia in a patient with acquired immunodeficiency syndrome]. Rev Clin Esp 1998;198:630-1.[PubMed]

4. Allen VD, Niec A, Kerem E, Greenberg M, Gold R. Rhodococcus equi pneumonia in a child with leukemia. Pediatr Infect Dis J 1989;8:656-8. [PubMed]

5. Alonso P, Tashima KT, Goldstein IJ. Photo quiz. Disseminated Rhodococcus equi infection. Clin Infect Dis 2001;32:929, 970-1. [PubMed]

6. Andersen SJ, Quan S, Gowan B, Dabbs ER. Monooxygenase-like sequence of a Rhodococcus equi gene conferring increased resistance to rifampin by inactivating this antibiotic. Antimicrob Agents Chemother 1997;41218-21. [PubMed]

7. Andersson AM, Weiss N, Rainey F, Salkinoja-Salonen MS. Dust-borne bacteria in animal sheds, schools and children's day care centres. J Appl Microbiol 1999;86:622-34. [PubMed]

8. Antinori S, Esposito R, Cernuschi M, Galli M, Galimberti L, Tocalli L, Moroni M. Disseminated Rhodococcus equi infection initially presenting as foot mycetoma in an HIV-positive patient. Aids 1992;6:740-2.[PubMed]

9. Arlotti M, Zoboli G, Moscatelli GL, Magnani G, Maserati R, Borghi V, Andreoni M, Libamore M, Bonazzi L, Piscina A, Ciammarughi R. Rhodococcus equi infection in HIV-positive subjects: a retrospective analysis of 24 cases. Scand J Infect Dis 1996;28:463-7. [PubMed]

10. Baraia-Etxaburu J, Malero P, Unzaga MJ, Teira R, Munoz J, Cisterna R, Santamaria JM. [Pneumonia caused by Rhodococcus equi in patients with AIDS: difficulty in defining the most appropriate initial treatment]. Enferm Infecc Microbiol Clin 1997;15:274-5. [PubMed]

11. Barsotti M, Cupisti A, Morelli E, Meola M, Barsotti G. Sepsis from Rhodococcus equi successfully treated in a kidney transplant recipient. Nephrol Dial Transplant 1997;12:2002-4. [PubMed]

12. Barton MD, Hughes KL. Ecology of Rhodococcus equi. Vet Microbiol 1984;9:65-76. [PubMed]

13. Berna JD, Garcia-Medina V, Cano A, Guirao J, Lafuente A, Garcia-Orenes MC. [Rhodococcus equi pneumonia in patients with HIV infection: report of 2 cases and review of the literature]. Enferm Infecc Microbiol Clin 1996;14:177-80. [PubMed]

14. Bernabeu-Wittel M, Villanueva JL, Pachon J, Alarcon A, Lopez-Cortes LF, Viciana P, Cadaval F, Talegon A. Etiology, clinical features and outcome of splenic microabscesses in HIV-infected patients with prolonged fever. Eur J Clin Microbiol Infect Dis 1999;18:324-9. [PubMed]

15. Bishopric GA, d'Agay MF, Schlemmer B, Sarfati E, Brocheriou C. Pulmonary pseudotumour due to Corynebacterium equi in a patient with the acquired immunodeficiency syndrome. Thorax 1988;43:486-7. [PubMed]

16. Blanco J, Yebra M, Munoz R, Burillo A. [Cerebral abscess caused by Rhodococcus equi in an immunocompetent patient]. Enferm Infecc Microbiol Clin 1998;16:294-5. [PubMed]

17. Bowersock TL, Salmon SA, Portis ES, Prescott JF, Robison DA, Ford CW, Watts JL. MICs of oxazolidinones for Rhodococcus equi strains isolated from humans and animals. Antimicrob Agents Chemother 2000;44:1367-9. [PubMed]

18. Bowles PM, Woolcock JB, Mutimer MD. The effect of immunosuppression on resistance to Rhodococcus equi in mice. Vet Immunol Immunopathol 1989;22:369-78. [PubMed]

19. Broadway D, Duguid G, Matheson M, Garner A, Dart J. Rhodococcus keratitis. Br J Ophthalmol 1998;82:198-9. [PubMed]

20. Brown E, Hendler E. Rhodococcus peritonitis in a patient treated with peritoneal dialysis. Am J Kidney Dis 1989;14:417-8. [PubMed]

21. Byard RW, Thorner PS, Edwards V, Greenberg M. Pulmonary malacoplakia in a child. Pediatr Pathol 1990;10:417-24. [PubMed]

22. Canizares R, Esparcia AM, Roig P, Garcia A, Ortiz V, Martin C, Merino J. [Cavitated pulmonary lesions in a patient with human immunodeficiency virus infection]. Enferm Infecc Microbiol Clin 1999;17:141-2. [PubMed]

23. Capdevila JA, Bujan S, Gavalda J, Ferrer A, Pahissa A. Rhodococcus equi pneumonia in patients infected with the human immunodeficiency virus. Report of 2 cases and review of the literature. Scand J Infect Dis 1997;29:535-41. [PubMed]

24. Carpenter JL, Blom J. Corynebacterium equi pneumonia in a patient with Hodgkin's disease. Am Rev Respir Dis 1976;114:235-9. [PubMed]

25. Casado JL, Antela A, Sanchez JA, Hermida JM, Meseguer M. Acute mediastinitis due to Rhodococcus equi in a patient with human immunodeficiency virus infection. Eur J Clin Microbiol Infect Dis 1997;16:241-4. [PubMed]

26. Cascales Ramos P, Garcia Aguayo JM, Bunuel F, Ferriz P, Llorca E, de Rafael L. [Cavitated pneumonia caused by Rhodococcus equi in an HIV-positive female patient]. Enferm Infecc Microbiol Clin 1991;9:662-4. [PubMed]

27. Cecconi L, Mazzuoli G, Busi Rizzi E, Schinina V, Bordi E, Tocci G. [Rhodococcus equi pulmonitis in HIV+. A review of the literature and a case report]. Radiol Med (Torino) 1993;85:122-5. [PubMed]

28. Chavanet P, Bonnotte B, Caillot D, Portier H. Imipenem/teicoplanin for Rhodococcus equi pulmonary infection in AIDS patients. Lancet 1991;337:794-5. [PubMed]

29. Chiewchanvit S, Mahanupab P, Baosoung V, Khamwan C. Uncommon manifestations of opportunistic infections in an HIV infected patient. J Med Assoc Thai 1998;81:923-6. [PubMed]

30. Cid A, Jarque I, Salavert M, Martin G, Perez-Belles C, Sanz MA. Recurrent bacteremia caused by Rhodococcus equi in a non-neutropenic patient with acute myeloid leukemia in complete remission. Haematologica 2002;87:ECR03. [PubMed]

31. Clave D, Archambaud M, Rouquet RM, Massip P, Moatti N. [In vitro activity of twenty antibiotics against Rhodococcus equi]. Pathol Biol (Paris) 1991;39:424-8. [PubMed]

32. Cormican MG, Jones RN. Antimicrobial activity of cefotaxime tested against infrequently isolated pathogenic species (unusual pathogens). Diagn Microbiol Infect Dis 1995;22:43-8. [PubMed]

33. Cornish N, Washington JA. Rhodococcus equi infections: clinical features and laboratory diagnosis. Curr Clin Top Infect Dis 1999;19:198-215. [PubMed]

34. de Quiros JF, Telenti M, Fleites A, Moreno Torrico A, Figueroa E. [Rhodococcus equi pneumonia in a patient with acquired immunodeficiency syndrome]. Med Clin (Barc) 1991;96:541-3. [PubMed]

35. Decre D, Bure A, Pangon B, Phillippon A, Bergogne-Berezin E. In-vitro susceptibility of Rhodococcus equi to 27 antibiotics. J Antimicrob Chemother 1991;2:311-3. [PubMed]

36. Deglise-Favre A, Aubert G, Lucht F, perpoint B, Hocquart J, Decousus H, Queneau P. [Lung pseudotumor caused by Corynebacterium equi in an AIDS patient]. Presse Med 1990;19:966. [PubMed]

37. Delgado M, Sancho T, Andreu M, Ortega N, Garcia J. [Cavitating pneumonia in a patient infected with human immunodeficiency virus]. Enferm Infecc Microbiol Clin 2000;18:289-90. [PubMed]

38. DeMarais PL, Kocka FE. Rhodococcus meningitis in an immunocompetent host. Clin Infect Dis 1995;20:167-9. [PubMed]

39. Doig C, Gill MJ, Church DL. Rhodococcus equi--an easily missed opportunistic pathogen. Scand J Infect Dis 1991;23:1-6. [PubMed]

40. Donisi A, Suardi MG, Casari S, Longo M, Cadeo GP, Carosi G. Rhodococcus equi infection in HIV-infected patients. Aids 1996;10:359-62. [PubMed]

41. Echeverri C, Matherne J, Jorgensen JH, Fowler LJ. Fite stain positivity in Rhodococcus equi: yet another acid-fast organism in respiratory cytology--a case report. Diagn Cytopathol 2001;24:244-6. [PubMed]

42. Farina C, Ferruzzi S, Mamprin F, Vailati F. Rhodococcus equi infection in non-HIV-infected patients. Two case reports and review. Clin Microbiol Infect 1997;3:12-18. [PubMed]

43. Fernandez A, Santos J, Sanchez MA, Alfaro C. [Rhodococcus equi pneumonia in a patient with AIDS. Primary resistance to imipenem]. Enferm Infecc Microbiol Clin 1994;12: 471-2. [PubMed]

44. Fettar K, Foulet A, Maillard H, Prophette B, Kaswin R, Celerier P, Lebas FX, Fabiani B. [A pulmonary mass with a raging fever]. Ann Pathol 1998;18:61-2. [PubMed]

45. Fierer J, Wolf P, Seed L, Gay T, Noonan K, Haghighi P. Non-pulmonary Rhodococcus equi infections in patients with acquired immune deficiency syndrome (AIDS). J Clin Pathol 1987;40:556-8. [PubMed]

46. Fischer L, Sterneck M, Albrecht H, Krupski G, Polywka S, Rogiers X, Broelsch CE. Vertebral osteomyelitis due to Rhodococcus equi in a liver transplant recipient. Clin Infect Dis 1998;26:749-52. [PubMed]

47. Flepp M, Luthy R, Wust J, Steinke W, Greminger P. [Rhodococcus equi infection in HIV disease]. Schweiz Med Wochenschr 1989;119:566-74. [PubMed]

48. Frame BC, Petkus AF. Rhodococcus equi pneumonia: case report and literature review. Ann Pharmacother 1993;27:1340-2. [PubMed]

49. Gallen F, Kernaonet E, Foulet A, Goldstein A, Lebon P, Babinet F. [Pulmonary infection from Rhodococcus equi after renal transplantation.Review of the literature]. Nephrologie 1999;20:383-6. [PubMed]

50. Garcia-Martos P, Bascunana A, Benjumeda M, Guerrero F, Marin P, de la Rubia F. [Pneumonia caused by Rhodococcus equi in a patient with AIDS]. Enferm Infecc Microbiol Clin 1991;9:664. [PubMed]

51. Gazquez I, Garcia Gonzalez M, Pena JM, Rubio M, Nogues A. [A pulmonary abscess due to Rhodococcus equi in an AIDS patient]. Rev Clin Esp 1993;192:152. [PubMed]

52. Glaser CA, Angulo FJ, Rooney JA. Animal-associated opportunistic infections among persons infected with the human immunodeficiency virus. Clin Infect Dis 1994;18:14-24. [PubMed]

53. Golub B, Falk G, Spink WW. Lung abscess due to Corynebacterium equi. Report of first human infection. Ann Intern Med 1967;66:1174-7. [PubMed]

54. Gopaul D, Ellis C, Maki A, Jr., Joseph MG. Isolation of Rhodococcus rhodochrous from a chronic corneal ulcer. Diagn Microbiol Infect Dis 1988;10:185-90. [PubMed]

55. Goupil F, Foulet A, Maillard H, Varache N, Varache C, Plat M, Kaswin R, Minaud B, Lebas FX. [Pulmonary malacoplakia caused by Rhodococcus equi in AIDS: a case report]. Rev Pneumol Clin 1999;55:171-4. [PubMed]

56. Gray KJ, French N, Lugada E, Watera C, Gilks CF. Rhodococcus equi and HIV-1 infection in Uganda. J Infect 2000;41:227-31. [PubMed]

57. Guerrero MF, Ramos JM, Renedo G, Gadea I, Alix A. Pulmonary malacoplakia associated with Rhodococcus equi infection in patients with AIDS: case report and review. Clin Infect Dis 1999;28:1334-6. [PubMed]

58. Hafner R, Bethel J, Standiford HC, Follansbee S, Cohn DL, Polk RE, Mole L, Raasch R, Kumar P, Mushatt D, Drusano G. Tolerance and pharmacokinetic interactions of rifabutin and azithromycin. Antimicrob Agents Chemother 2001;45:1572-7. [PubMed]

59. Hamrock D, Azmi FH, O'Donnell E, Gunning WT, Philips ER, Zaher A. Infection by Rhodococcus equi in a patient with AIDS: histological appearance mimicking Whipple's disease and Mycobacterium avium-intracellulare infection. J Clin Pathol 1999;52:68-71. [PubMed]

60. Harvey RL, Sunstrum JC. Rhodococcus equi infection in patients with and without human immunodeficiency virus infection. Rev Infect Dis 1991;13:139-45. [PubMed]

61. Henriques J, Andre M, Santiago F, Pardal C, Abecassis M, Pina J. [Rhodococcus equi pneumonia in patients with AIDS]. Acta Med Port 2000;13:49-53. [PubMed]

62. Hillerdal G, Riesenfeldt-Orn I, Pedersen A, Ivanicova E. Infection with Rhodococcus equi in a patient with sarcoidosis treated with corticosteroids. Scand J Infect Dis 1988;20:673-7. [PubMed]

63. Hillidge CJ. Review of Corynebacterium (Rhodococcus) equi lung abscesses in foals: pathogenesis, diagnosis and treatment. Vet Rec 1986;119:261-4. [PubMed]

64. Hoque S, Weir A, Fluck R, Cunningham J. Rhodococcus equi in CAPD-associated peritonitis treated with azithromycin. Nephrol Dial Transplant 1996;11:2340-1. [PubMed]

65. Hsueh PR, Hung CC, Teng LJ, Yu MC, Chen YC, Wang HK, Luh KT. Report of invasive Rhodococcus equi infections in Taiwan, with an emphasis on the emergence of multidrug-resistant strains. Clin Infect Dis 1998;27:370-5. [PubMed]

66. Hulsewe-Evers HP, Jansveld CA, Jansz AR, Schneider MM, Bravenboer B. HIV-infected patient with a Rhodococcus equi pneumonia. Neth J Med 2000;57:25-9. [PubMed]

67. Ibarra R, Jinkins JR. Severe otitis and mastoiditis due to Rhodococcus equi in a patient with AIDS. Case report. Neuroradiology 1999;41:699-701. [PubMed]

68. Jablonowski H, Armbrecht C, Mauss S, Szelenyi H, Manegold C, Borchard F, Niederau C. Rhodococcus equi pneumonia in an HIV-infected patient. Bildgebung 1994;61:206-9. [PubMed]

69. Jacks S, Giguere S, Gronwall PR, Brown MP, Merritt KA. Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals. Am J Vet Res 2001;62:1870-5. [PubMed]

70. Jensen KT, Schonheyder H, Pers C, Thomsen VF. In vitro activity of teicoplanin and vancomycin against gram-positive bacteria from human clinical and veterinary sources. Apmis 1992;100:543-52. [PubMed]

71. Johnson DH, Cunha BA. Rhodococcus equi pneumonia. Semin Respir Infect 1997;12:57-60. [PubMed]

72. Kayser FH, Morenzoni G, Strassle A, Hadorn K. Activity of meropenem, against gram-positive bacteria. J Antimicrob Chemother 1989;24 Suppl A:101-12. [PubMed]

73. Kedlaya I, Ing MB, Wong SS. Rhodococcus equi infections in immunocompetent hosts: case report and review. Clin Infect Dis 2001;32:E39-46. [PubMed]

74. Kenney DG, Robbins SC, Prescott JF, Kaushik A, Baird JD. Development of reactive arthritis and resistance to erythromycin and rifampin in a foal during treatment for Rhodococcus equi pneumonia. equine Vet J 1994;26:246-8. [PubMed]

75. Kim SC, Jorgensen J, Graybill JR, Smith J. Otomastoiditis caused by Rhodococcus equi in a patient with AIDS. P R Health Sci J 1999;18:285-8. [PubMed]

76. Kristinsson JK, Sigurdsson H, Sigfusson A, Gudmundsson S, Agnarsson BA. Detection of orbital implant infection with technetium 99m-labeled leukocytes. Ophthal Plast Reconstr Surg 1997;13:256-8. [PubMed]

77. Kwa AL, Tam VH, Rybak MJ. Rhodococcus equi pneumonia in a patient with human immunodeficiency virus: case report and review. Pharmacotherapy 2001;21:998-1002. [PubMed]

78. La Rocca E, Gesu G, Caldara R, Maffi P, Del Maschio A, Vanzulli A, Castoldi R, DiCarlo V, Pozza G, Secchi A. Pulmonary infection caused by Rhodococcus equi in a kidney and pancreas transplant recipient: a case report. Transplantation 1998;65:1524-5. [PubMed]

79. Lambert C, Gansler T, Mansour KA, Schwartzmann SW, Duffell GM, Gal AA. Pulmonary malakoplakia diagnosed by fine needle aspiration. A case report. Acta Cytol 1997;41:1833-8. [PubMed]

80. Lanzafame M, Bonora S, Di Perri G, Allegranzi B, Guasparri I, Cazzadori A, Ferrari S, Vento S, Concia E. Microsporidium species in pulmonary cavitary lesions of AIDS patients infected with Rhodococcus equi. Clin Infect Dis 1997;25:926-7. [PubMed]

81. LeBar WD, Pensler MI. Pleural effusion due to Rhodococcus equi. J Infect Dis 1986;154:919-20. [PubMed]

82. Legras A, Lemmens B, Dequin PF, Cattier B, Besnier JM. Tamponade due to Rhodococcus equi in acquired immunodeficiency syndrome. Chest 1994;106:1278-9. [PubMed]

83. Libanore M, Rossi MR, Bicocchi R, Ghinelli F. Rhodococcus equi pneumonia and occult HIV infection. Lancet 1993;342:496-7. [PubMed]

84. Linares MJ, Lopez-Encuentra A, Perea S. Chronic pneumonia caused by Rhodococcus equi in a patient without impaired immunity. Eur Respir J 1997;10:248-50. [PubMed]

85. Linder R. Rhodococcus equi and Arcanobacterium haemolyticum: two "coryneform" bacteria increasingly recognized as agents of human infection. Emerg Infect Dis 1997;3:145-53. [PubMed]

86. Lopes Cardoso FL, Machado ES, Souza MJ, Cunha R. Rhodococcus equi mastoiditis in a patient with AIDS. Clin Infect Dis 1996;22:713. [PubMed]

87. Lortholary O, Mainardi JL, La Scola B, Gallais V, Frenaux P, Casassus P. Consecutive bacillary angiomatosis and Rhodococcus equi bacteremia during acute leukemia: zoonoses may cause fever in neutropenic patients. Clin Microbiol Infect 2000;6:334-6. [PubMed]

88. MacGregor JH, Samuelson WM, Sane DC, Godwin JD. Opportunistic lung infection caused by Rhodococcus (Corynebacterium) equi. Radiology 1986;160:83-4. [PubMed]

89. Macias J, Pineda JA, Borderas F, Gallardo JA, Delgado J, Leal M, Sanchez-Quijano A, Lissen E. Rhodococcus or mycobacterium? An example of misdiagnosis in HIV infection. Aids 1997;11:253-4. [PubMed]

90. Magnani G, Elia GF, McNeil MM, Brown JM, Chezzi C, Gabrielli M, Fanti F. Rhodococcus equi cavitary pneumonia in HIV-infected patients: an unsuspected opportunistic pathogen. J Acquir Immune Defic Syndr 1992;5:1059-64. [PubMed]

91. Marsh HP, Bowler IC, Watson CJ. Successful treatment of Rhodococcus equi pulmonary infection in a renal transplant recipient. Ann R Coll Surg Engl 2000;82:107-8. [PubMed]

92. Martin MP, Moragrega B, Garcia M, Castillon E. [Rhodococcus equi brain abscess in a patient in hemodialysis]. Nefrologia 2000 Jul-Aug;20:387-8. [PubMed]

93. Martin-Davila P, Quereda C, Rodriguez H, Navas E, Fortun J, Mesequer M, Moreno A, Guerrero A. Thyroid abscess due to Rhodococcus equi in a patient infected with the human immunodeficiency virus. Eur J Clin Microbiol Infect Dis 1998;17:55-7. [PubMed]

94. Mattei P, Beguinot I, Malet T, Evon P, Lion C, Hoen B. [Meningitis, septicemia and endophthalmitis caused by Streptococcus equi subspecies zooepidemicus]. Presse Med 1995;24:1089. [PubMed]

95. Matteo Rigolin G, Bigoni R, Spanedda R, Castoldi G, Rossi MR. An unusual case of untreated chronic lymphocytic leukemia patient presenting with Rhodococcus equi bacteriemia. Am J Hematol 1996;52:126. [PubMed]

96. McNeil MM, Brown JM. Distribution and antimicrobial susceptibility of Rhodococcus equi from clinical specimens. Eur J Epidemiol 1992;8:437-43. [PubMed]

97. Messias A, Araujo C, Lino S, Pacheco T, Masinho K, Ordway D, Ventura FA. [Cavitated pulmonary condensation by Rhodococcus equi, in an HIV seropositive individual]. Acta Med Port 2000;13:329-35. [PubMed]

98. Meynard JL, Salord JM, Lesage D, Kirstetter M, Frottier J, Petit JC. [Rhodococcus equi pneumonia: 1st opportunistic manifestation in a patient infected with HIV-1]. Ann Med Interne (Paris) 1992;143:216-8. [PubMed]

99. Mohammedi I, Vedrinne JM, Floccard B, Reverdy ME, Duperret S, Motin J. Disseminated Rhodococcus equi and Nocardia farcinica infection in a patient with sarcoidosis. J Infect 1998;36:134-5. [PubMed]

100. Munoz P, Burillo A, Palomo J, Rodriguez-Creixems M, Bouza E. Rhodococcus equi infection in transplant recipients: case report and review of the literature. Transplantation 1998;65:449-53. [PubMed]

101. Muntaner L, Leyes M, Payeras A, Herrera M, Gutierrez A. Radiologic features of Rhodococcus equi pneumonia in AIDS. Eur J Radiol 1997;24:66-70. [PubMed]

102. Nasser AA, Bizri AR. Chronic scalp wound infection due to Rhodococcus equi in an immunocompetent patient. J Infect 2001;42:67-8. [PubMed]

103. Nordmann P, Kerestedjian JJ, Ronco E. Therapy of Rhodococcus equi disseminated infections in nude mice. Antimicrob Agents Chemother 1992;36:1244-8. [PubMed]

104. Nordmann P, Nicolas MH, Gutmann L. Penicillin-binding proteins of Rhodococcus equi: potential role in resistance to imipenem. Antimicrob Agents Chemother 1993;37:1406-9. [PubMed]

105. Nordmann P, Ronco E. In-vitro antimicrobial susceptibility of Rhodococcus equi. J Antimicrob Chemother 1992;29:383-93. [PubMed]

106. Novak RM, Polisky EL, Janda WM, Libertin CR. Osteomyelitis caused by Rhodococcus equi in a renal transplant recipient. Infection 1988;16:186-8. [PubMed]

107. Obana WG, Scannell KA, Jacobs R, Greco C, Rosenblum ML. A case of Rhodococcus equi brain abscess. Surg Neurol 1991;35:321-4. [PubMed]

108. Perrymore WD, Milton WJ. Dense Rhodococcus cerebral abscesses in an HIV-positive patient. Neuroradiology 1997;39:581-2. [PubMed]

109. Pialoux G, Dupont B. [Lung abscess caused by Rhodococcus equi in HIV infection: two cases]. Presse Med 1992;21:1086. [PubMed]

110. Piersantelli N, Casini-Lemmi M, Cavanna E, Cassola G, Crisalli MP, Guida B, Paladino M, Penco G, Piscopo R, Torresin A. [Rhodococcus equi infections in AIDS: personal cases]. Pathologica 1992;84:517-21. [PubMed]

111. Prescott JF. The susceptibility of isolates of Corynebacterium equi to antimicrobial drugs. J Vet Pharmacol Ther 1981;4:27-31. [PubMed]

112. Prescott JF. Rhodococcus equi: an animal and human pathogen. Clin Microbiol Rev 1991;4:20-34. [PubMed]

113. Prescott JF, Nicholson VM. The effects of combinations of selected antibiotics on the growth of Corynebacterium equi. J Vet Pharmacol Ther 1984;7:61-4. [PubMed]

114. Prescott JF, Sweeney CR. Treatment of Corynebacterium equi pneumonia of foals: a review. J Am Vet Med Assoc 1985;187:725-8. [PubMed]

115. Roca V, Vinuelas J, Perez-Cecilia E, Picardo A, Rabadan PM, Ortega L, Torres A, Picazo JJ. [Bacteremic pneumonia caused by Rhodococcus equi and HIV infection. Report of a new case and review of the literature]. Enferm Infecc Microbiol Clin 1991;9:627-9. [PubMed]

116. Rodriguez Arrondo F, von Wichmann MA, Arrizabalaga J, Iribarren JA, Garmendia G, Idigoras P. [Pulmonary cavitation lesions in patients infected with the human immunodeficiency virus: an analysis of a series of 78 cases]. Med Clin (Barc) 1998;111:725-30. [PubMed]

117. Rouquet RM, Clave D, Massip P, Moatti N, Leophonte P. Imipenem/vancomycin for Rhodococcus equi pulmonary infection in HIV-positive patient. Lancet 1991;337:375. [PubMed]

118. Rouveix E, Dupont C, Ichai P, Nicolas MH, Julie C, Lesur G, Dorra M. [Two particular aspects of Rhodococcus equi infection: malacoplakia and acquisition of resistance to antibiotics]. Presse Med 1992;21:1086. [PubMed]

119. Sabater L, Andreu H, Garcia-Valdecasas JC, Moreno A, Vila J, Rimola A, Grande L, Navasa M, Visa J, Rodes J. Rhodococcus equi infection after liver transplantation. Transplantation 1996;61:980-2. [PubMed]

120. Sanchez JF, Ojeda I, Martin C, Sanchez F, Vinuelas J. [Bacteremic pneumonia due to Rhodococcus equi in a patient with human immunodeficiency virus infection and visceral leishmaniasis]. Enferm Infecc Microbiol Clin 1999;17:532-3. [PubMed]

121. Sane DC, Durack DT. Infection with Rhodococcus equi in AIDS. N Engl J Med 1986;314:56-7. [PubMed]

122. Sasal M, Roig J, Cervantes M, Matas L, Segura F. Good response to antibiotic treatment of lung infection due to Rhodococcus equi in a patient infected with human immunodeficiency virus. Clin Infect Dis 1992;15:747-8. [PubMed]

123. Schilz RJ, Kavuru MS, Hall G, Winkelman E. Spontaneous resolution of rhodococcal pulmonary infection in a liver transplant recipient. South Med J 1997;90:851-4. [PubMed]

124. Schneider E, Farber CM, Struelens MJ, Van Vooren JP. Long survival of a patient with AIDS in spite of previous Rhodococcus equi infection. Acta Clin Belg 1997;52:50. [PubMed]

125. Schneider MM. Change in natural history of opportunistic infections in HIV-infected patients. Neth J Med 2000;57:1-3. [PubMed]

126. Schwartz DA, Ogden PO, Blumberg HM, Honig E. Pulmonary malakoplakia in a patient with the acquired immunodeficiency syndrome. Differential diagnostic considerations. Arch Pathol Lab Med 1990;114:1267-72. [PubMed]

127. Scott MA, Graham BS, Verrall R, Dixon R, Schaffner W, Tham KT. Rhodococcus equi--an increasingly recognized opportunistic pathogen. Report of 12 cases and review of 65 cases in the literature. Am J Clin Pathol 1995;103:649-55. [PubMed]

128. Scotton PG, Tonon E, Giobbia M, Gallucci M, Rigoli R, Vaglia A. Rhodococcus equi nosocomial meningitis cured by levofloxacin and shunt removal. Clin Infect Dis 2000;30:223-4. [PubMed]

129. Shapiro JM, Romney BM, Weiden MD, White CS, O'Toole KM . Rhodococcus equi endobronchial mass with lung abscess in a patient with AIDS. Thorax 1992;47:62-3. [PubMed]

130. Shin MS, Cooper JA Jr., Ho KJ. Pulmonary malacoplakia associated with Rhodococcus equi infection in a patient with AIDS. Chest 1999;115:889-92. [PubMed]

131. Sigler E, Miskin A, Shtlarid M, Berrebi A. Fever of unknown origin and anemia with Rhodococcus equi infection in an immunocompetent patient. Am J Med 1998;104:510. [PubMed]

132. Simsir A, Oldach D, Forest G, Henry M. Rhodococcus equi and cytomegalovirus pneumonia in a renal transplant patient: diagnosis by fine-needle aspiration biopsy. Diagn Cytopathol 2001;24:129-31. [PubMed]

133. Sirera G, Romeu J, Clotet B, Velasco P, Arnal J, Rius F, Foz M. Relapsing systemic infection due to Rhodococcus equi in a drug abuser seropositive for human immunodeficiency virus. Rev Infect Dis 1991;13:509-10. [PubMed]

134. Sladek GG, Frame JN. Rhodococcus equi causing bacteremia in an adult with acute leukemia. South Med J 1993;86:244-6. [PubMed]

135. Stolk-Engelaar MV, Dompeling EC, Meis JF, Hoogkamp-Korstanje JA. Disseminated abscesses caused by Rhodococcus equi in a patient with chronic lymphocytic leukemia. Clin Infect Dis 1995;20:478-9. [PubMed]

136. Sughayer M, Ali SZ, Erozan YS, Dunsmore N, Hall GS. Pulmonary malacoplakia associated with Rhodococcus equi infection in an AIDS patient. Report of a case with diagnosis by fine needle aspiration. Acta Cytol 1997;41:507-12. [PubMed]

137. Sweeney CR, Sweeney RW, Divers TJ. Rhodococcus equi pneumonia in 48 foals: response to antimicrobial therapy. Vet Microbiol 1987;14:329-36. [PubMed]

138. Szabo B, Miszti C, Majoros L, Nabradi Z, Gomba S. Isolation of rare opportunistic pathogens in Hungary: case report and short review of the literature. Rhodococcus equi. Acta Microbiol Immunol Hung 2000;47:9-14.[PubMed]

139. Takai S, Takeda K, Nakano Y, Karasawa T, Furugoori J, Sasaki Y, Tsubaki S, Higuchi T, Anzai T, Wada R, Kamada M. Emergence of rifampin-resistant Rhodococcus equi in an infected foal. J Clin Microbiol 1997;35:1904-8. [PubMed]

140. Takasugi JE, Godwin JD. Lung abscess caused by Rhodococcus equi. J Thorac Imaging 1991;6:72-4. [PubMed]

141. Talanin NY, Donabedian H, Kaw M, O'Donnell ED, Zaher A. Colonic polyps and disseminated infection associated with Rhodococcus equi in a patient with AIDS. Clin Infect Dis 1998;26:1241-2. [PubMed]

142. Tang S, Lo CY, Lo WK, Ho M, Cheng IK. Rhodococcus peritonitis in continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant 1996;11:201-2. [PubMed]

143. Tomlin P, Sand C, Rennie RP. Evaluation of E test, disk diffusion and broth microdilution to establish tentative quality control limits and review susceptibility breakpoints for two aerobic actinomycetes. Diagn Microbiol Infect Dis 2001;40:179-86. [PubMed]

144. Tsang KW, Lam PS, Yuen KY, Ooi CC, Lam W, Ip M. Rhodococcus equi lung abscess complicating Evan's syndrome treated with corticosteroid. Respiration 1998;65:327-30. [PubMed]

145. Tunger A, Ozkan F, Vardar F, Burhanoglu D, Ozinel MA, Tokbas A. Purulent meningitis due to Rhodococcus equi. A case of posttraumatic infection. Apmis 1997;105:705-7. [PubMed]

146. Verville TD, Huycke MM, Greenfield RA, Fine DP, Kuhls TL, Slater LN. Rhodococcus equi infections of humans. 12 cases and a review of the literature. Medicine (Baltimore) 1994;73:119-32. [PubMed]

147. Volpino P, Lonardo MT, Cangemi R, Di Martino M, Clementi M, Cangemi V. Rhodococcus equi pneumonia in a patient with occult HIV infection: successful therapy. Panminerva Med 1997;39:61-3. [PubMed]

148. von Graevenitz A, Punter-Streit V. Development of a new selective plating medium for Rhodococcus equi. Microbiol Immunol 1995;39:283-4. [PubMed]

149. Votava M, Skalka B, Hrstkova H, Tejkalova R, Dvorska L. [Review of 105 cases of isolation of Rhodococcus equi in humans]. Cas Lek Cesk 1997;136:51-3. [PubMed]

150. Weingarten JS, Huang DY, Jackman JD, Jr. Rhodococcus equi pneumonia. An unusual early manifestation of the acquired immunodeficiency syndrome (AIDS). Chest 1988;94:195-6. [PubMed]

151. Wicky S, Cartei F, Mayor B, Frija J, Gevenosis PA, Giron J, Laurent F, Perri G, Schnyder P. Radiological findings in nine AIDS patients with Rhodococcus equi pneumonia. Eur Radiol 1996;6:826-30. [PubMed]

152. Woolcock JB, Farmer AM, Mutimer MD. Selective medium for Corynebacterium equi isolation. J Clin Microbiol 1979;9:640-2. [PubMed]

153. Woolcock JB, Mutimer MD. Corynebacterium equi: in vitro susceptibility to twenty-six antimicrobial agents. Antimicrob Agents Chemother 1980;18:976-7. [PubMed]

154. Zhao HK, Hiramune T, Kikuchi N, Yanagawa R, Ito S, Hatta T, Serikawa S, Oe Y. Selective medium containing fosfomycin, nalidixic acid, and culture supernatant of Rhodococcus equi for isolation of Corynebacterium pseudotuberculosis. Zentralbl Veterinarmed [B] 1991;38:743-8. [PubMed]