Options and limitations of teicoplanin in febrile granulocytopenic patients

Summary During the years 1985–89 three studies on the efficacy and safety of teicoplanin in the treatment of febrile granulocytopenic patients suffering from haematological malignancies were assessed. In the first prospective study, teicoplanin at a dose of 400 mg/d was added to the initial empiric therapy of 65 febrile granulocytopenic episodes. When teicoplanin was given because of proven or presumed Gram-positive infection, 67% of cases were treated successfully. Patients with skin and soft-tissue infections achieved a 78% response rate. The second study on 120 patients was designed as a prospective randomized trial to compare the efficacy and toxicity of ceftazidime with and without teicoplanin. Response was achieved in 25/51 (49%) cases from the ceftazidime and in 33/52 cases (63%) from the combination groups. Seven of 18 (39%) cases with initial bacteraemia in the monotherapy group compared with 10/20 (50%) cases in the combination group responded to the empiric regimen. A retrospective analysis was carried out on the efficacy of teicoplanin in 125 cases of proven Gram-positive Hickman line-associated bacteraemia. Teicoplanin proved to be effective in eradicating 80% of the Staphylococcus epidermidis. 72% of the Staph. aureus, 90% of the ‘viridans’ streptococci and 67% of the enterococci. Removal of the catheter was required in 13% of cases in order to control the infection, and only one patient died of a catheter-related septicaemia caused by Staph. aureus. The total success rate leaving the catheter in situ was 78%, and 92% if cases with catheter removal were included. Serum levels of teicoplanin were predictable giving a peak and trough concentration on the fourth day of 30.4 ± 5.0 mg/l and 9.8 ± 1.7 mg/l. Hearing loss of 20 dB at 8000 Hz was noted in one case and transient liver or kidney disturbances attributable to the drug were observed in 4% of cases.     

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.     

Teicoplanin in the treatment of Gram-positive bacteraemia in neutropenic patients

S ummary The increasing incidence of bacteraemia caused by Gram-positive bacteria in neutropenic patients prompted the authors to evaluate, in a prospective trial, the role of teicoplanin in the treatment of this infection. Over a 15-month period. 76 cases of bacteraemia (out of 265 evaluable episodes of fever) were observed at the Division of Haematology. University La Sapienza. Kome. Of the 76 cases studied, 46 (60%) were caused by Gram-positive bacteria and 28 (37%) were caused by Gram-negative bacilli. All febrile episodes were treated randomly and empirically with piperacillin plus amikacin with or without teicoplanin. Overall, 41 (54%) of the 76 cases of bacteraemia responded to the initial antibiotic regimen: with subsequent modifications the response rate rose to 96%.
In the treatment of Gram-positive bacteraemia. first-line administration of teicoplanin was found to be associated with early defervescence and with a significantly higher rate of success without modification of treatment (P < 0.01). Addition of teicoplanin as second-line therapy produced a favourable outcome in 12 (70%) out of 17 cases of bacteraemia unresponsive to the initial piperacillin + amikacin regimen. No cases of Gram-positive bacteraemia associated with septic shock or adult respiratory distress syndrome were observed in either treatment group. Only two late deaths were observed, and these occurred in patients with streptococcal septicaemia who were not receiving early teicoplanin.
The above data do not endorse the use of glycopeptide antibiotics in the early treatment of fever in neutropenic patients: rather, these compounds should be reserved for proven or presumed Gram-positive infections which do not respond to initial beta-lactam/aminoglycoside treatment.     

Ceftazidime plus teicoplanin versus ceftazidime plus amikacin as empiric therapy for fever in cancer patients with granulocytopenia

S ummary In a prospective randomized study, 100 episodes of fever (>38°C) and granulocytopenia (<1000/μ1) in cancer patients were empirically treated with ceftazidime (2 g every 8 h) plus teicoplanin (400 mg every 8 h on day 1: 400 mg every day thereafter) or ceftazidime (2 g every 8 h) plus amikacin (500 mg every 8 h).
Bacteraemia. clinically documented infection and possible infection were documented in seven. 11 and 19 patients treated with ceftazidime plus teicoplanin and in 11, four and 17 patients treated with ceftazidime plus amikacin. Overall, the response rate was similar in the two groups of patients as was the need for treatment modifications and the rate of death.
For documented Gram-positive bacteraemia, the response rate was 2/5 patients treated with ceftazidime plus teicoplanin and 2/7 with ceftazidime plus amikacin: for documented Gram-negative bacteraemia. the response rate was 1/2 and 3/4 patients respectively. No breakthrough bacteraemia was observed. Tolerance was excellent. although renal toxicity (elevation of serum creatinine) was observed in three patients treated with ceftazidime plus teicoplanin and in none allocated to ceftazidime plus amikacin.     

A randomized study of teicoplanin plus ciprofloxacin versus gentamicin plus piperacillin for the empirical treatment of fever in neutropenic patients

S ummary We compared the combination of teicoplanin plus ciprofloxacin with gentamicin plus piperacillin for the empirical treatment of fever in 80 neutropenic patients. A favourable clinical response rate was achieved in 28/38 (74%) patients receiving teicoplanin plus ciprofloxacin and in 17/ 35 (49%) of those receiving gentamicin plus piperacillin (P = 0.05). Microbiologically documented infections accounted for 55% of febrile events. When these episodes were analysed separately, response to teicoplanin plus ciprofloxacin remained unchanged at 74% whereas only 35% patients responded to gentamicin and piperacilin (P=0.034). Gram-positive organisms accounted for 78% bacterial isolates with Staphylococcus epidermidis the most common pathogen. Ten out of 12 (83%) Staph. Epidermidis infections resolved when treated with teicoplanin and ciprofloxacin as compared with a response rate of only two out of eight (75%) with gentamicin and piperacillin (P = 0.032). The combination of teicoplanin and ciprofloxacin was associated with no severe drug-related adverse events: by contrast, two patients receiving gentamicin plus piperacilin were withdrawn owing to adverse drug reactions, one with acute renal failure and one following a severe allergic reaction to piperacillin. We conclude that teicoplanin with ciprofloxacin is more effective than gentamicin plus piperacillin for the empirical treatment of febrile neutropenic patients. The high incidence of Gram-positive infection in our unit probably justifies the use of a specific anti-Gram-positive agent in the first-line antibiotic regimen.     

Amikacin plus piperacillin versus ceftazidime as initial therapy in granulocytopenic patients with presumed bacteremia

69 febrile granulocytopenic episodes without an initial focus of infection were assessed for empiric treatment either with high-dose amikacin plus piperacillin or ceftazidime. 90% of patients in each group survived the granulocytopenic episode; 15 (44 +/- 17%) episodes treated with the combination and 23 (66 +/- 16%) given ceftazidime responded without any modification of initial therapy and half defervesced within 72 h. Persistent fever was the most frequent reason for altering treatment which was done empirically in 90% of cases, but two-thirds of patients required further treatment modification. An infectious focus mainly involving the lung developed during granulocytopenia in 21 patients (30%), of which 17 occurred during antimicrobial therapy. Only 1 infection was shown to be due to bacteria, while 7 were due to fungi. Amikacin levels were similar to those expected following a normal dose (mean peak of 34.7 and mean trough of 12.6 mg/l). Therapy with the combination resulted in a higher serum creatinine (p less than 0.001) and a lower potassium level (p less than 0.001) in comparison with monotherapy. Potassium supplementation was required in 45 +/- 17% of patients given the combination compared with only 4 +/- 7% of those treated with ceftazidime. While both regimens appeared to be equally effective as initial therapy, the need for modification was high in both patient groups. Monotherapy being both simpler to administer and less toxic seems therefore to be the logical choice although the period of empiric therapy must be fully exploited in order to improve diagnosis and therefore antimicrobial management.     

Ceftazidime plus amikacin versus ceftazidime plus vancomycin as empiric therapy in febrile neutropenic children with cancer

Two antibiotic regimens, ceftazidime plus amikacin and ceftazidime plus vancomycin, were compared in a prospective, randomized clinical trial as empiric therapy in febrile granulocytopenic children with cancer. The rate of response was similar in the two groups (66% vs. 77%). The prevalence of secondary gram-negative bacteremia was higher--but not significantly higher--in the group receiving vancomycin. Adverse reactions also occurred more often in the latter group (35% vs. 4%). Mortality did not differ significantly in the two groups. Adjustment for independent predictors of response to treatment by means of multivariate analysis confirmed the lack of any remarkable difference between the responses to the two regimens. We conclude that the use of vancomycin instead of amikacin in combination with ceftazidime does not significantly improve the outcome of treatment of fever and infection in granulocytopenic children with cancer and that the use of vancomycin is associated with an increased frequency of both secondary infections due to gram-negative bacteria and adverse reactions.     

A randomized clinical trial of ceftriaxone and teicoplanin versus ceftazidime and teicoplanin as antibiotic therapy in febrile neutropenic cancer patients and bone marrow transplant recipients

Summary A prospective, randomized clinical trial comparing combination therapy with ceftriaxone and teicoplanin versus ceftazidime and teicoplanin in the treatment of febrile episodes in neutropenic cancer patients and bone marrow transplant recipients was performed. One hundred and two patients were randomized, but two patients were considered unevaluable for efficacy, and three patients were withdrawn due to incorrect randomization. Of the remaining 97 patients, infection resolved without modification of therapy in 31/49 (63%) patients treated with ceftriaxone/teicoplanin versus 27/48 (56%) patients treated with ceftazidime/teicoplanin (P=0.48). Of all 97 patients treated therapy was modified in 18/49 (36%) with ceftriaxone/teicoplanin and 21/48 (43%) with ceftazidime/teicoplanin. Nineteen patients treated with ceftriaxone/teicoplanin received netilmicin and 21 patients treated with ceftazidime/teicoplanin also received netilmicin according to the study design (escalation therapy). When netilmicin was added infection resolved in 78% of patients treated with ceftriaxone/teicoplanin versus 84% of those treated with ceftazidime/teicoplanin. It was concluded that combination therapy with ceftriaxone/teicoplanin is an alternative to combination therapy with ceftazidime/teicoplanin, and has the advantage of once daily administration.

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Antibiotische Therapie der febrilen Neutropenie von Tumor- und Knochenmarktransplantationspatienten. Eine randomisierte Studie mit Ceftriaxon und Teicoplanin im Vergleich mit Ceftazidim und Teicoplanin

Zusammenfassung In einer prospektiven, randomisierten klinischen Studie wurde die Kombinationstherapie mit Ceftriaxon und Teicoplanin gegen die Kombinationspartner Ceftazidim und Teicoplanin bei neutropenischen Patienten oder Patienten nach Knochenmarktransplantation verglichen. Insgesamt wurden 101 Patienten in die Studie eingebracht, davon waren 97 Patienten auswertbar. In der Ceftriaxon/Teicoplanin-Gruppe waren 63% der Patienten geheilt, gegenüber 56% der Patienten in der Ceftazidim/Teicoplanin-Gruppe. Dieses Ergebnis war ohne Modifikation der Studien-Medikamente erreicht worden. Bei 18 von 49 Patienten in der Ceftriaxon/Teicoplanin-Gruppe und 21 von 48 Patienten in der Ceftazidim/Teicoplanin-Gruppe wurde von der Studienmedikation abgegangen und zusätzlich Netilmicin (Eskalationstherapie) gegeben. Durch die zusätzliche Gabe von Netilmicin waren 78% der Patienten in der Ceftriaxon/Teicoplanin-Gruppe und 84% in der Ceftazidim/Teicoplanin-Gruppe geheilt. Diese Daten deuten darauf hin, daß die Kombinationstherapie mit Ceftriaxon/Teicoplanin eine Alternative zur Kombinationstherapie mit Ceftazidim und Teicoplanin darstellt, zumal die Gabe von Ceftriaxon und Teicoplanin den Vorteil hat, daß diese Medikamente nur einmal pro Tag gegeben werden müssen.

     

A multi-centre prospective study of febrile neutropenia in Norway: microbiological findings and antimicrobial susceptibility

The urgent need to treat presumptive bacterial or fungal infections in neutropenic patients has meant that initial therapy is empiric and based on the pathogens most likely to be responsible, and drug resistance. The traditional empirical treatment in Norway has been penicillin G and an aminoglycoside, and this combination has been criticized over recent y. We wished to analyse the microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in febrile neutropenic patients. This was a prospective multicentre study. During the study period of 2 y, a total of 282 episodes of fever involving 243 neutropenic patients was observed. In 34% of episodes bacteraemia was documented. Overall, 40% of the episodes were caused by Gram-positive organisms, 41% by Gram-negative organisms and 19% were polymicrobial. The most frequently isolated bacteria were Escherichia coli (25.6%), a- and non-haemolytic streptococci (15.6%), coagulase-negative staphylococci (12.4%) and Klebsiella spp. (7.4%). None of the Gram-negative isolates was resistant to gentamicin, meropenem, ceftazidime or ciprofloxacin. Only 5 coagulase-negative staphylococci isolates were resistant to both penicillin G and aminoglycoside. The overall mortality rate was 7%, and 1.2% due to confirmed bacteraemic infection.     

Empiric therapy with amphotericin B in febrile granulocytopenic patients

The early diagnosis of invasive fungal infection in granulocytopenic patients remains unreliable. Granulocytopenic patients who are persistently or recurrently febrile despite therapy with appropriate antibacterial agents are at high risk for the development of such infection. Two randomized clinical trials demonstrated that the empiric administration of amphotericin B to persistently or recurrently febrile granulocytopenic patients decreased the frequency, morbidity, and mortality of invasive fungal infection; these effects were especially marked in profoundly granulocytopenic patients who were not receiving antifungal prophylaxis. Current studies continue to indicate that prompt empiric administration of amphotericin B to persistently or recurrently febrile granulocytopenic patients ensures earlier treatment of deep mycoses. The roles of newer antifungal triazole compounds and of liposomal and lipid complexes of amphotericin B in empiric antifungal therapy must be investigated further in thoughtfully designed, randomized clinical trials.     

Ceftazidime with or without amikacin for the empiric treatment of localized infections in febrile,granulocytopenic patients

Summary In a prospective randomized study, 90 granulocytopenic febrile patients presenting with a localized infection were treated empirically with ceftazidime alone or in combination with amikacin (1.5 g/day). Two thirds had received selective oral antimicrobial prophylaxis before therapy. The treatment groups were comparable in terms of the depth and duration of granulocytopenia as well the distribution of the infection categories and rate of bacteremia. There was no difference with respect to the final response: 53% for the monotherapy group versus 48% for the combination group, and both regimens appeared to be equally safe. The duration of fever, clinical symptoms, antibiotic therapy, and granulocytopenia were comparable for both treatment groups, and approximately 90% of patients survived the infection. Only one patient given monotherapy required amikacin. It is concluded that aminoglycosides are not necessary for the empiric treatment of infectious complications in granulocytopenic patients if antibacterial prophylaxis has been given before-hand.J. P. Donnelly is supported by Glaxo Group Research, London, United Kingdom     

Ceftazidime and amikacin as empiric treatment of febrile episodes in neutropenic patients in Saudi Arabia.

Sixty-four consecutive febrile episodes in 50 consecutive patients with malignancy and neutropenia were empirically treated with a combination of ceftazidime and amikacin. Of 52 analysable episodes, the response rate was 59.6% overall and 26.3% of episodes with microbiologically documented infections with septicaemia. Infection-related death occurred in 10 patients (19.2% of episodes). The response rates were similar in patients with acute leukaemia or other malignancies. Poor response is attributed to increased frequency of infections with Gram-positive and fungal organisms. A modified empiric regimen including cover for Gram-positive and fungal organisms is suggested in similar patient populations.     

Ceftazidime monotherapy for empiric treatment of febrile neutropenic patients: a meta-analysis.

Whether ceftazidime monotherapy is equal in efficacy to combination regimens (Comb) for empiric treatment of febrile neutropenic patients was tested using meta-analysis. Published studies and abstracts of ceftazidime trials were identified, their quality assessed, the efficacy data abstracted and pooled, and effects of patient and study characteristics examined. The pooled odds ratio (OR) of failure of ceftazidime for febrile episodes was 1.27 (95% confidence interval [CI]: 0.79-2.03; n = 1077) and for bacteremic episodes was 0.72 (CI, 0.33-1.58; n = 248; OR less than 1.0 favors ceftazidime). Results were not significantly affected by type of antibiotic in Comb, age, neutropenia (less than 500/mm3), study quality, or combining abstracts. Results indicate that Comb does not offer a significant advantage over ceftazidime. A subgroup of profoundly neutropenic (less than 100/mm3) patients could not be assessed, raising the possibility that in this important subgroup monotherapy and Comb may not be equivalent. Use of ceftazidime empirically may require modification based on microbiologic results and clinical course.     

A clinical trial on efficacy and safety of teicoplanin in combination with beta-lactams and aminoglycosides in the treatment of severe sepsis of patients undergoing allogeneic/autologous bone marrow transplantation

S ummary Early institution of empiric therapy with a broad-spectrum antibiotic has markedly reduced the morbidity and mortality from infections complicating severe or prolonged cytopenia in patients receiving either an allogeneic or autologous hone marrow transplant. Ceftazidime in combination with an aminoglycoside, i.e. netilmicin, has been established as a combination schedule offering low or even avoiding therapy-related toxicity.
We evaluated teicoplanin for suspected Gram-positive infections after inadequate response to initial beta-lactam and aminoglycoside combination therapy. All 11 patients so far included in this study received either an allogeneic (five patients) or an autologous (six patients) bone marrow transplant for acute myeloid leukaemia (AML). non-Hodgkin lymphoma (NHL. high grade) or other malignant diseases. All patients developing a primary septicaemia of unknown origin (10 patients) or a catheter related septicaemia (one patient) were treated with 400 mg teicoplanin, administered i.v. once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g. i.v., t.i.d., netilmicin 400 mg once daily). All 11 patients responded to therapy. 10 patients were clinically cured, one patient improved under therapy. The therapeutic regimen was well tolerated and adverse drug reactions did not occur. We have not observed any delayed take or prolonged neutropenia or thrombocytopenia with this therapeutic regimen when compared to other bone marrow transplant patients who did not receive this antimicrobial therapy.
Our preliminary results suggest that teicoplanin is a potentially effective and well-tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta-lactams and aminoglycosides.     

Empiric antibiotic therapy for suspected infection in granulocytopenic cancer patients: a comparison between the combination of moxalactam plus amikacin and ticarcillin plus amikacin

Moxalactam is a new cephalosporin with a broad spectrum of activity which includes Pseudomonas aeruginosa in addition to Klebsiella species Escherichia coli, and Staphylococcus aureus. Moxalactam was combined with amikacin (M + A) compared to ticarcillin plus amikacin (T + A) in a prospective, randomized double-blind trial of empiric therapy for febrile episodes among granulocytopenic cancer patients. One hundred and ninety-one epidoses were evaluated; T + A, 93 episodes and M + A, 98 episodes. Median granulocyte count of initiation of therapy was less than 100/microliters. Overall response rates were good. In the T + A group, 21 of 29 (72 percent) microbiologically documented infections, including seven of 14 (50 percent) bacteremias, and 24 of 27 (89 percent) clinically documented infections improved. In the M + A group, 20 of 28 (71 percent) microbiologically documented infections, including 11 of 18 (61 percent) bacteremias, and 25 of 25 (96 percent) clinically documented infections resolved. Adverse effects were minimal and equivalent in both groups. Hypokalemia (decrease in serum potassium of greater than 11 mEq/liter from baseline) occurred in 14 of the 93 episodes in the T + A group and in 10 of the 98 episodes in the M + A group with decline in mean serum potassium level of 0.5 and 0.4 mEq/liter respectively. Nephrotoxicity (increase in serum creatinine greater than 0.04 mg/dl) occurred in only one patient in the T + A group and in two patients in the M + A group. Moxalactam plus amikacin has a broader in vitro spectrum, is as effective, and is no more toxic than ticarcillin plus amikacin as empiric therapy for febrile granulocytopenic cancer patients.     

Concurrent bacteraemia and malaria in febrile Nigerian infants

In the tropics, febrile illnesses are often presumed to be due to malaria, because of its endemicity, and treatment can lead to delay in diagnosis or failure to detect severe infections such as bacteraemia.This study sought to determine the prevalence of bacteraemia and malaria parasitaemia in febrile post-neonatal infants (age 1-12 months) at the University College Hospital, Ibadan, Nigeria, and the bacterial aetiological agents of bacteraemia in the infants. Therefore, 102 infants aged 1-12 months who presented with fever with a negative history of antimicrobial use in the week prior to presentation were evaluated and had blood cultures done for the detection of aerobic organisms by standard methods and blood films for malaria parasites. Bacteraemia was found in 38.2% of the infants, malaria parasitaemia was found in 46.1%.The most common organisms isolated were Escherichia coli (35.9%), Staphylococcus aureus (33.3%) and Klebsiella spp. (10.3%). Febrile children should be investigated for the presence of bacterial infection even if the blood film for malaria parasites is positive. Where laboratory facilities are not available, consideration should be given to the use of both anti-malarial therapy and empiric antibiotic therapy in the management of febrile infants, depending on the clinician's judgement.     

Empirical antimicrobial monotherapy in patients after high-dose chemotherapy and autologous stem cell transplantation: a randomised, multicentre trial

We report on 232 patients undergoing autologous haematopoietic stem cell transplantation (ASCT) entered into a multicentre, randomised trial comparing the efficacy and tolerability of meropenem (MPM) with that of piperacillin/tazobactam (P/T) as empirical antimicrobial first-line therapy for febrile neutropenia. In 27.6% of patients in the MPM group and 22.4% in the P/T group, therapy was initially supplemented with a glycopeptide for venous catheter infection or bacteraemia because of coagulase-negative staphylococci. Complete response rate after 72 h was 63.8% in the MPM group and 49.6% in the P/T group (P = 0.034). Overall complete response rate after treatment modification was 94.0% in the MPM group and 93.1% in the P/T group. Median time to defervescence was 2 d in the MPM group and 3 d in the P/T group. The most frequently isolated pathogens were Gram-positive cocci. Treatment was well tolerated in both groups. One patient (0.4%) died from infection. Empirical first-line therapy with MPM as well as with P/T is safe and effective in febrile episodes emerging after ASCT. Higher response rates to primary treatment can be achieved with MPM.     

Bacteremia in granulocytopenic patients in a tertiary-care general hospital

Episodes of bacteremia in granulocytopenic patients during 1985 and 1986 at a tertiary-care general hospital were reviewed to assess the adequacy of current empiric antimicrobial therapy. The major pathogens in these cases were Pseudomonas aeruginosa, Enterobacteriaceae organisms, and Staphylococcus epidermidis. This combination of pathogens differed from that found at the same facility from 1975 to 1977, when Staphylococcus aureus and streptococci predominated. When apparent, the sources of infection were predominantly venous catheters, the lower respiratory tract, and the urinary tract; most frequently there was no identifiable focus. S. epidermidis and streptococci were isolated more frequently during initial episodes of febrile bacteremia, and P. aeruginosa was isolated more often during subsequent episodes. If a narrow definition for therapeutic outcome is used, only 38% of episodes had a favorable response; response rates were no different with appropriate or inappropriate therapy. The low response rate may have been related to the use of data from the previous review to guide empiric therapy and to the subsequent inadequate treatment of infections caused by Pseudomonas and Enterobacter organisms. The overall mortality per total bacteremic episodes was 19%, and the primary factor associated with mortality was pneumonia (P less than .0001). This study emphasizes the need for ongoing surveillance of local patterns of bacteremia to direct empiric therapy.     

替考拉宁药代动力学指导重症G＋菌感染患者个体化用药的临床分析

目的探讨替考拉宁药代动力学指导个体化用药在重症G^＋感染患者中的优势。 方法选取西部战区总医院确诊为重症G^＋感染患者80例,随机分成替考拉宁标准组与优化组各40例。用高效液相色谱法(HPLC)进行血药浓度监测(TDM)。标准组按说明书给药,优化组在药代动力学指导下个体化给药。比较两组患者第3、6剂谷浓度及目标谷浓度达标率、AUC_0-24/MIC≥125、345的达标率、第1、4天体温、炎性指标、细菌清除率、结局指标、药物不良反应等,评价其疗效及安全性。 结果HPLC法标准曲线方程式：Y＝14.316X＋2.881 (r²＝0.9999,n＝6)。与标准组比较,优化组第6剂谷浓度及达标率更高(11.16±3.16 mg/L vs. 8.96±4.10 mg/L, 82.5% vs. 32.5%,P<0.05);AUC_0-24/MIC≥345达标率更优(67.5% vs. 27.5%,P<0.05);第1、4天WBC、CRP下降更快;细菌清除率更佳(80% vs. 55%,P<0.05);治疗总有效率更好(85% vs. 65%,P<0.05)。与谷浓度密切相关的是给药剂量(kg,mg/kg)和肌酐清除率(CLcr, ml/min)。拟合方程式：LogC₃＝0.405＋0.068 kg₃－0.001 CLcr₃(VIF 1.023,R²＝61.8%,P<0.001),LogC₆＝0.92＋0.042 kg₆－0.004 CLcr₆(VIF 1,R²＝73.5%,P<0.001)。 结论HPLC法进行TDM准确、可靠。替考拉宁药代动力学指导的个体化用药治疗重症G^＋感染患者疗效高,安全性好。拟合方程式可为临床用药提供参考。     

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