Oral cefixime is similar to continued intravenous antibiotics in the empirical treatment of febrile neutropenic children with cancer.

Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization, but the safety of this approach has not been adequately studied in children. We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation. Two hundred episodes of febrile neutropenia were studied (156 patients), and 100 episodes were randomized to receive each treatment. Failure to respond to therapy was defined by documented or suspected bacterial infection, recurrent fever, or discontinuation of assigned therapy for any reason before neutropenia resolved. Rates of treatment failure were similar in the oral cefixime group (28%) and in the iv antibiotic group (27%; P=1.0). Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children, a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment.     

Ceftazidime as first-line therapy for fever in acute leukaemia

Fifty patients with acute non-lymphocytic leukaemia were treated by random allocation with either ceftazidime alone or a combination of piperacillin, netilmicin and cefotaxime for 65 febrile neutropenic episodes. Nineteen of 33 patient episodes (58%) responded to ceftazidime alone compared with 21 of 32 episodes (66%) treated with the combination. There was one infective death in a patient given the combination; rates of documented superinfection were low. The treatment groups appeared identical in terms of patient demography, underlying disease and other risk factors, though patients with a clinical site of infection responded more slowly than those without. Bacteraemia per se did not appear to influence outcome. Bactericidal serum concentrations greater than or equal to 8 X the minimum bactericidal concentration were predictive of a rapid response (within 4 days) to antibiotics. Furthermore, serum from patients treated with ceftazidime maintained adequate cidal activity against Pseudomonas aeruginosa for longer than that obtained from patients treated with the three-drug combination. Ceftazidime was shown to be a safe and effective alternative to the three-drug combination for the initial management of febrile neutropenic episodes in leukaemic patients.     

A prospective study on the epidemiology of febrile episodes during chemotherapy-induced neutropenia in children with cancer or after hemopoietic stem cell transplantation.

BACKGROUND: The purpose of our study was to evaluate the incidence and clinical characteristics of febrile episodes during neutropenia following chemotherapy in children with cancer. PATIENTS AND METHODS: A prospective, 3-year single-center observational study of periods of neutropenia was performed. Epidemiology and clinical diagnoses of febrile episodes occurring during the neutropenic periods were evaluated, taking into consideration different categories of anticancer treatment based on the type of tumor and phase of therapy. RESULTS: A total of 703 febrile episodes were observed during 614 (34%) of 1792 neutropenic periods (34%), for a total of 28,001 days at risk, accounting for a rate of 0.76 episodes per 30 days at risk. The highest proportions of neutropenic periods with primary febrile episodes were observed after autologous hemopoietic stem cell transplantation (58%), aggressive treatment for acute leukemia or non-Hodgkin lymphoma (48%), and allogeneic hemopoietic stem cell transplantation (44%); the lowest proportion (9%) was observed during maintenance chemotherapy for acute leukemia (P<.001). The most frequent clinical diagnosis was fever of unknown origin (in 79% of cases), followed by bacteremia (10%); invasive mycosis was diagnosed in only 2% of cases. CONCLUSIONS: The overall incidence of febrile neutropenia and severe infectious complications in children with cancer is low, with differences according to the aggressiveness of chemotherapy. This fact must be considered when designing clinical trials on the management of infectious complications in children with cancer.     

Using teicoplanin for empiric therapy of febrile neutropenic patients with haematological malignancies

S ummary The cumulative experience with teicoplanin in treating febrile neutropenic patients included in three different comparative clinical trials conducted at a single institution during a 3-year period, is presented. 1 52 febrile episodes in 129 neutropenic patients were treated with iv. teicoplanin (6 mg/kg/d) combined with amikacin (15 mg/kg/d) plus ceftazidime (90 mg/kg/d). The study population comprised 75 patients with acute leukaemia and 77 marrow recipients: 53(% (81/152) had a central venous catheter in place and 68%) (103/152) had severe neutropenia (< 100/mm³) at the beginning of the febrile episode.
The overall response rate of the evaluiable febrile episodes was excellent: 88% (107/122) improved. Bacteraemias due to Gram-positive cocci accounted for 75% of the total (42/56) and pathogens in the blood isolates were mostly staphylo-cocci (coagulase-negative 14, coagulase-positive 13) and streptococci (131. The response rate of Gram-positive bacteraemias was good: 88% (37/42) improved and 75% (9/12) of Gram-positive bacteraemias having teicoplanin as the only antibiotic with in vitro activity against the infective strains were cured. Death due to infection accounted for 7% of total febrile episodes (11/152). Side effects were documented in 14(%, of the episodes. In a setting of high prevalence of Grampositive infections caused by strains with a high rate of resistance to aminoglycoside and betalactam antibiotics, there may be an advantage in including teicoplanin in the initial empiric antibiotic regimen for febrile neutropenic cancer patients.     

Cost-effectiveness of ceftazidime or imipenem/cilastatin versus ceftriaxone+aminoglycoside in the treatment of febrile episodes in neutropenic cancer patients in Germany

Summary A three-pronged cost-effectivess analysis of the treatment of febrile episodes in neutropenic cancer patients was conducted. It included a review of 37 randomized, controlled studies in the MEDLINE and EMBASE databases (1980–1996). Clinical outcomes as well as costs of treatment with imipenem/cilastatin, ceftazidime and ceftriaxone+aminoglycoside were compared. Primary therapy and modification, respectively, were successful in 62 and 27% of patients treated with imipenem/cilastatin, in 56 and 31% with ceftazidime and in 41 and 13% with ceftriaxone+aminoglycoside. From the perspective of a 1,800-bed teaching hospital, the average overall cost per successfully treated patient was DM 7,475 with imipenem/cilastatin, DM 7,810 with ceftazidime and DM 8,963 with ceftriaxone+netilmicin (DM 1=USD 0.56; 7/97). The costs for the German national economy were imipenem/cilastatin DM 23,828, ceftazidime DM 24,985 and ceftriaxone+netilmicin DM 29,838.     

Cefotaxime versus Ampicillin,Methicillin and Netilmicin in Combination for Treatment of Febrile Episodes in Patients with Haematologic Malignancy

ABSTRACT A prospective, randomized trial comparing treatment of 61 febrile episodes with cefotaxime (CTX) versus a combination of ampicillin, methicillin, and netilmicin (AMN) was carried out in 58 patients with leukaemia or malignant lymphoma, of whom 28 had a granulocyte count of 500×10⁶/I. The overall response frequency was 63% for CTX against 49% for the AMN combination, the latter figure being lower than generally reported in the literature. The difference was not statistically significant. In 21 episodes pathogens were isolated, 16 of them from the blood. All isolated bacteria but one, a strain of Bacteroides fragilis, were fully sensitive to at least one of the three antibiotics in the combination, and all but one, a strain of Listeria monocytogenes, were fully sensitive to CTX. These results indicate that CTX seems to be a promising alternative as monotherapy for empiric treatment of febrile episodes in patients with haematologic malignancies. Further investigations will, however, be required before completely rational choices between mono and combination therapy of febrile episodes in immuno-suppressed patients can be made.     

An assessment of the efficacy of antimicrobial prophylaxis in bone marrow autografts.

Fifty-three patients undergoing autologous bone marrow transplantation received antimicrobial prophylaxis with ciprofloxacin with or without erythromycin and low dose intravenous amphotericin B. Eight patients remained afebrile throughout the neutropenic period. All other patients had one or more febrile episodes. The median time to fever after the onset of neutropenia was 7 days. There were no gram-negative organisms isolated from blood cultures during any of these episodes whereas gram-positive organisms were isolated in 28. There was one death in this series associated with sepsis. The use of low-dose prophylactic parenteral amphotericin did not prevent the subsequent successful use of full dose amphotericin for antibiotic-resistant fever. Ciprofloxacin effectively prevents gram-negative sepsis. The addition of erythromycin does little to prevent gram-positive sepsis. The use of regimens with agents with activity against gram-positive organisms is appropriate initial treatment of all febrile neutropenic episodes.     

Procalcitonin in paediatric cancer patients: its diagnostic relevance is superior to that of C-reactive protein, interleukin 6, interleukin 8, soluble interleukin 2 receptor and soluble tumour necrosis factor receptor II

Sensitive parameters of inflammation are rare in neutropenic cancer patients. In this study, procalcitonin (PCT), C-reactive protein (CRP), interleukin 6 (IL-6), IL-8, the soluble IL-2 receptor (sIL-2R) and the soluble tumour necrosis factor receptor II (sTNFRII) were evaluated for their diagnostic relevance in febrile episodes of cancer patients. Plasma or serum levels of these parameters were determined in neutropenic children with febrile episodes (n = 122) classified according to both the kind of infection [60 cases of fever of unknown origin (FUO), 28 cases of localized infection, 13 cases of pneumonia, 20 cases of bacteraemia, one case of fungaemia] and the World Health Organization (WHO) score of chemotherapy-induced mucositis. At baseline and during the febrile episodes, the highest levels of all parameters were observed in cases of gram-negative bacteraemia. However, in FUO and localized infections, low or only slightly elevated median levels of all parameters were documented. The degree of chemotherapy-induced mucositis did not influence the value of any parameter. In comparison with the other inflammatory parameters, PCT (optimum cut-off level 0.5 microg/l) was a more sensitive and more specific parameter in the diagnosis of high-risk (gram-negative bacteraemia) and low-risk (FUO) episodes, as well as in the sequential assessment of all febrile neutropenic episodes.     

Measurement of C-reactive protein in adults with febrile neutropenia after hematopoietic cell transplantation

The aim of this study was to evaluate the usefulness of C-reactive protein (CRP) monitoring in the differential diagnosis and prognosis of febrile neutropenic episodes in hematopoietic cell transplantation (HCT). In all, 100 patients were enrolled in the study. The CRP was determined in serum every 48 h from admission until resolution of the febrile episode. All patients presented with fever during the post-HCT neutropenic period. The febrile episodes were classified as microbiologically documented infection in 32 cases, clinically documented infection in 27 patients and fever of unknown origin in 41 patients. The mean CRP values on the first day of fever in these three groups were similar (NS). On the fifth day of antibiotic treatment, 50 patients remained pyrexial. Of these, 41 improved with modifications of antibiotherapy (mean CRP: 9.5 mg/dl; standard deviation (s.d.): 6.2) and nine died, five due to an infectious etiology (CRP: 21 mg/dl; s.d.: 4.4; P<0.003) and four from other causes (CRP: 11 mg/dl; s.d.: 3.4). On multivariate analysis, the CRP on the fifth day of treatment was an independent prognostic factor for fatal outcome. We conclude that persistent elevation of the CRP is an independent factor predicting a fatal outcome in patients who remain febrile on the fifth day of antibiotherapy during neutropenic febrile episodes post-HCT.     

Bacteremia in patients with febrile neutropenia after chemotherapy at a university medical center in Malaysia.

OBJECTIVES: This study was initiated to determine the local profile of blood culture isolates and antibiotic sensitivities in febrile neutropenic patients following chemotherapy, and to establish if any modifications to treatment guidelines are necessary. DESIGN: A total of 116 episodes of febrile neutropenia admitted to the adult hematology ward at a university medical center in Malaysia were studied retrospectively from January 2004 to January 2005. RESULTS: The study showed 43.1% of febrile neutropenic episodes had established bacteremia. Gram-negative bacteria accounted for 60.3% of isolates. Sensitivities of Gram-negative bacteria to the antibiotics recommended in the Infectious Diseases Society of America (IDSA) guidelines were 86.1-97.2%. Coagulase-negative staphylococci were the most common Gram-positive organisms isolated (23.3%). The majority of these were methicillin-resistant. CONCLUSIONS: Carbapenem monotherapy, as recommended in the 2002 IDSA guidelines, is effective treatment for the infections most often encountered at our center. Combination therapy with an aminoglycoside should be considered when using ceftazidime, cefepime or piperacillin-tazobactam, particularly in high-risk patients. Vancomycin should be used if a Gram-positive organism is suspected or isolated.     

Monotherapy or aminoglycoside-containing combinations for empirical antibiotic treatment of febrile neutropenic patients: a meta-analysis

We set out to compare the efficacy of antibiotic monotherapy with that of combination therapy including an aminoglycoside for empirical treatment of febrile neutropenic cancer patients. We did a meta-analysis of 29 randomised clinical trials pooling data from 4795 febrile episodes and a subset of 1029 bacteraemic episodes by both fixed and random effects models. Outcome measure was clinical failure of antibiotic treatment, defined as modification of the initially allocated regimen or death during treatment. In febrile episodes, the pooled odds ratio (OR) of clinical failure with monotherapy versus combination therapy was 0.88, with 95% CI from 0.78 to 0.99 by the fixed effects model, and 0.87 with 95% CI from 0.75 to 1.01 by the more conservative random effects model. For bacteraemic episodes, the pooled OR of failure with monotherapy was 0.70 (0.54 to 0.92) by the fixed effects model, and 0.72 (0.54 to 0.95) by the random effects model. We conclude that monotherapy has been as effective as aminoglycoside-containing combinations for empirical treatment of febrile neutropenia.     

The efficacy and safety of piperacillin-tazobactam for febrile neutropenic patients in Japan

The IDSA guideline for management of febrile neutropenic patients updated in 2010 recommends monotherapy with anti-pseudomonal-lactam agents, including piperacillin-tazobactam (PIPC/TAZ) for high-risk patients. However, clinical studies of PIPC/TAZ are limited in Japanese patients. In this study, we conducted an open-labeled non-randomized prospective trial to examine the efficacy and safety of PIPC/TAZ as an empirical treatment for Japanese patients with febrile neutropenia. Forty-nine febrile episodes in neutropenic patients excluding those undergoing allogeneic stem cell transplantation (high risk 36, low risk 13) were analyzed. The overall response rate was 71%, and no significant differences between the high-risk and the low-risk group were observed (high risk 72%, low risk 69%). Neither PS nor usage of G-CSF affected the response rate. No major side effects were observed in the study. The efficacy and the safety profile of PIPC/TAZ treatment were comparable to those in other previous Western studies. In conclusion, this study suggests PIPC/TAZ is effective and well tolerated as an initial empirical treatment for febrile neutropenic Japanese patients.     

Imipenem-cilastatin for empirical therapy in neutropenic patients with fever: an open study in patients with hematologic malignancies

In adult neutropenic patients with hematological malignancies, we explored imipenem-cilastatin as empirical antibiotic therapy in a dose of 500 mg four times daily. Changing to second-line treatment was only resorted to if clinical deterioration, new infections or recurrence of fever occurred. A clinically or microbiologically documented infection was apparent in 115 of 150 episodes studied (76.7%). Imipenem-cilastatin was successful in 70.7% of all episodes and in 67.8% of all proven infections. Modification was necessary and successful in 22.0% of all episodes. 11 patients died while still febrile, 6 of them by infection (4%) and 5 because of progressive disease (3.3%). Imipenem-cilastatin is safe initial therapy in neutropenic febrile patients.     

Prospective evaluation of procalcitonin in adults with febrile neutropenia after haematopoietic stem cell transplantation

Serum procalcitonin (PCT) levels have been proposed as a new discriminative marker for bacterial and fungal infections. We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation (HSCT). PCT was determined prospectively in 92 febrile episodes, classified according to the final diagnosis as: neutropenic fever of unknown origin (n = 51), microbiological (n = 26) or clinical (n = 5) documented infection and non-infectious febrile episodes (n = 10). On first day of fever, mean (+/- SD) PCT level was 0.3 ng/ml (0.2) in neutropenic fever of unknown origin, 0.5 ng/ml (0.7) in microbiologically confirmed infections, 0.2 ng/ml (0.2) in clinically documented infections and 1.7 (4.2) in non-infectious fever (P = not significant). Five days after the antibiotic therapy was started, fever persisted in 29 neutropenic episodes (32%). Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [10.1 ng/ml (6.7)] than all remaining groups (P = 0.027; Kruskal-Wallis). Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode. However, when fever persisted for more than 5 d, PCT values > or = 3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis.     

Clinical characteristics and antibiotic susceptibility of viridans streptococcal bacteremia in children with febrile neutropenia

Purpose

This retrospective study was performed in order to investigate the clinical characteristics and antibiotic susceptibility of viridans streptococcal bacteremia (VSB) in febrile neutropenic children in the context of the increase in incidence and antibiotic resistance of VSB.

Methods

We conducted this study among neutropenic children with underlying hematology/oncology diseases who were diagnosed with VSB at a single institution from April 2009 to June 2012. Clinical and laboratory characteristics of the children as well as antibiotic susceptibility of the causative viridans streptococci were evaluated.

Results

Fifty-seven episodes of VSB were diagnosed in 50 children. Severe complications occurred in four children (7.0 %), and a death of one child (1.8 %) was attributable to VSB. Acute myeloid leukemia was the most common underlying disease (70.2 % of all cases), and 71.9 % of all cases received chemotherapy including high-dose cytarabine. VSB occurred at a median of 13 days (range 8–21 days) after the beginning of chemotherapy, and fever lasted for a median of 4 days (range 1–21 days). The C-reactive protein level significantly increased within a week after the occurrence of VSB (p < 0.001) and the maximum C-reactive protein level showed a positive correlation with fever duration (r = 0.362, p = 0.007). Second blood cultures were done before the use of glycopeptides in 33 children, and negative results were observed in 30 children (90.9 %). Susceptibilities to cefotaxime, cefepime, and vancomycin were 58.9, 69.1, and 100 %, respectively.

Conclusions

Severe complications of VSB in neutropenic febrile children were rare. We suggest glycopeptide use according to the results of blood culture and antibiotic susceptibility tests based on the susceptibility to cefepime and the microbiologic response to empirical antibiotic treatment not including glycopeptides in this study.     

Aztreonam therapy in neutropenic patients with cancer

Combinations of aztreonam/vancomycin, aztreonam/vancomycin/amikacin, and moxalactam/ticarcillin were compared in a prospective randomized trial as empiric therapy for febrile neutropenic cancer patients. Vancomycin was added to aztreonam to provide coverage against gram-positive organisms. Of 535 febrile episodes included in the study, 455 were evaluable. The aztreonam/vancomycin and aztreonam/vancomycin/amikacin combinations were both more effective than the moxalactam/ticarcillin combination in a total of 244 episodes of documented infection. The difference was due to the fact that both aztreonam-containing combinations were more effective than the moxalactam/ticarcillin combination in documented gram-positive infections. The three regimens were equally effective in 67 documented infections due to a single gram-negative bacterial species. (The response rates were 87, 86 and 94 percent for the aztreonam/vancomycin, aztreonam/vancomycin/amikacin, and moxalactam/ticarcillin combinations, respectively.) Aztreonam was effective as the single active antibiotic in the treatment of gram-negative infections in neutropenic patients; however, it must be used in combination with another antibiotic to provide gram-positive coverage.     

A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients.

BACKGROUND--Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile. The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent (monotherapy). The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside (amikacin) to either of these agents would provide an advantage. METHODS--A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin. Efficacy analysis was done for 750 assessable episodes. A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors. RESULTS--The overall response rates were 76% with imipenem plus amikacin, 72% with imipenem, 71% with ceftazidime plus amikacin, and 59% with ceftazidime alone. Single-organism gram-positive infections occurred in 101 of 750 episodes. Without a change in antibiotics, the response rates were 50% with imipenem, 40% with imipenem plus amikacin, 39% with ceftazidime plus amikacin, and 38% with ceftazidime. Most responded to vancomycin or other antibiotics, and the mortality associated with gram-positive infections was only 5%. Regardless of the antibiotic regimen, the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond. Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors. CONCLUSIONS--Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer.     

Combination of Amikacin and either Ampicillin or Cephalotin as Initial Treatment of Febrile Neutropenic Patients

ABSTRACT. A prospective, randomized trial of two antibiotic combinations (amikacin plus either ampicillin or cephalotin) was performed on 39 consecutive episodes of fever in 30 patients with neutropenia and hematological malignancy. Infections were documented as the cause of fever in 37 episodes (95%): in 21 episodes (54%) bacteria or a virus (n=1) were isolated, and in 16 (41% of all episodes) the infection was documented clinically but no pathogen was isolated. The most frequently isolated bacteria were Staph, aureus (38% of all strains), E. coli (13%), and Pseudomonas aeruginosa (13%). Bacteremia occurred in 18% of the febrile episodes. Improvement followed treatment with the combination amikacin plus ampicllin in 73% of 19 cases, and with amikacin plus cephalotin in 55% of 20 cases (p>0.05), giving a total Improvement rate of 64%. Failure of therapy was seen in episodes caused by multiple bacteria or Pseudomonas infections. Mild signs of nephrotoxicity were noted in 13% during both regimens. Audiograms were normal in all but two patients who showed slight high-frequency hearing loss. A second infection occurred in 7 episodes (18%). Thus, the combination of amikacin plus ampidllin was as efficient (but less expensive) as amikacin plus cephalotin in the initial treatment of febrile episodes in neutropenic patients with hematological malignancies.     

Treatment of chronic pseudomonas aeruginosa infection in cystic fibrosis patients with ceftazidime and tobramycin

50% inhibitory concentration (IC50) and minimum inhibitory concentration (MIC) of ceftazidime, cefsulodin, cefotaxime, moxalactam, azlocillin, carbenicillin, netilmicin and tobramycin against 90 strains of Pseudomonas aeruginosa isolated from cystic fibrosis (CF) patients were determined by means of the agar plate dilution method. Ceftazidime was most active of the antibiotics in vitro; the geometric mean of IC50 was 0.2 and of MIC 0.4 micrograms/ml. 11 CF patients suffering from P. aeruginosa infection were treated with 14 day courses of ceftazidime (100 mg/kg/24 h) and tobramycin (10 mg/kg/24 h). P. aeruginosa was only temporarily eradicated in one of the patients, but a significant improvement of respiratory function and a significant fall in white blood cell count was recorded in the patients during chemotherapy. There was no development of resistant strains against ceftazidime during treatment and no side-effects were observed. Ceftazidime is a promising new antimicrobial agent with high in vitro activity which deserves further in vivo evaluation in CF patients.     

肿瘤患者粒细胞缺乏症并感染的经验性抗生素治疗回顾性分析

目的　总结肿瘤患者粒细胞缺乏症并感染的经验性抗生素治疗的临床经验。方法　回顾性分析 119例肿瘤患者 2 4 8例次的临床资料 ,观察头孢哌酮 (CFP)、氧哌嗪青霉素 (PPC)、头孢他定 (CTZ)、亚胺培南 (IMP)与丁胺卡那霉素 (AMK)分别组成BA、PA、CA、TA方案的疗效及副作用。结果　BA、PA、CA、TA方案分别治疗 10 3、87、35和 2 3例次 ,治疗的中位时间为 7～ 8d ,有效率分别为 6 3%、4 8%、6 8%和 74 % ,PA方案明显为低 (P <0 0 5 )。治疗无效者调整治疗 :改用CA或TA方案加减去甲万古霉素 (NVC)及抗真菌治疗 ;总有效率分别为 88%、83%、86 %和 91%。最常见副作用为胃肠功能紊乱 ,腹泻为 12 % ,皮疹和肝转氨酶轻度升高分别为 4 % ;2例NVC和AMK治疗者出现明显的听力下降和肾脏毒性。结论　BA、CA、TA方案具有相似的疗效 ,可作为一线经验性治疗方案。经验性治疗无效者 ,应改用具有更高抗菌活性的方案或尽早采用NCV和 (或 )抗霉菌治疗