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1.
Bacterial infections remain a common complication of hematopoietic stem cell transplantation (HSCT), especially in the pre-engraftment phase. The risk of bacterial infections is mainly related to neutropenia, mucositis, and the presence of vascular lines. Most parts of the world have witnessed a shift in epidemiology toward Gram-negative bacteria; a large proportion of which are resistant to fluoroquinolones, extended-spectrum beta-lactams, carbapenems, and in some units even colistin. Meticulous infection control practices are essential for prevention of bacterial infections in HSCT. The role of routine prophylactic antibiotics is limited in settings with high rates of bacterial resistance. If used, prophylactic antibiotics should be limited to high-risk patients, and the agents are selected based on local resistance profiles. Neutropenic fever is a medical emergency in most HSCT recipients. Prompt clinical evaluation is paramount, along with the intravenous administration of appropriate empiric antimicrobials, typically an antipseudomonal beta-lactam agent. Glycopeptides should only be considered if the patient is hemodynamically unstable or Gram-positive infection is suspected. Additional Gram-negative agents, such as colistin or aminoglycosides, may be added if extensive Gram-negative resistance is expected. To mitigate increasing bacterial resistance, empiric antibiotic regimens should be rationalized or discontinued as soon as possible.  相似文献   

2.
Pseudomonas aeruginosa is a well-known cause of severe and potentially life-threatening infections among hematological patients. A prospective epidemiological surveillance program ongoing at our Hematology Unit revealed an increase over time of P. aeruginosa bloodstream infections (BSI). Their impact on outcome and antibiotic susceptibility was analyzed. BSI which consecutively occurred at our institution during a 70-month period were evaluated and correlated with type of pathogen, status of underlying disease, neutropenia, previous antibiotic therapy, resistance to antibiotics, and outcome. During the observation period, 441 BSI were recorded. Frequency of Gram-negative BSI was higher than that of other pathogens (57.3%). Overall, 66 P. aeruginosa BSI were recorded; 22 out of 66 were multiresistant (MR P. aeruginosa). Thirty-day mortality for all BSI was 11.3%; it was 27.3% for P. aeruginosa BSI and 36.4% for MR P. aeruginosa. At multivariate analysis, only active hematological disease and P. aeruginosa BSI were associated to an increased risk of death. For MR P. aeruginosa, BSI mortality was 83.3% vs. 18.8% when empiric therapy included or not an antibiotic with in vitro activity against P. aeruginosa (p=0.011). Together with active disease, the emergence of P. aeruginosa BSI, particularly if multiresistant, was responsible for an increased risk of death among hematological patients at our institution. In this scenario, reconsidering the type of combination antibiotic therapy to be used as empiric treatment of neutropenic fever was worthwhile.  相似文献   

3.
The purpose of this study was to test the comparative efficacy and toxicity of empiric gentamicin and ciprofloxacin, in combination with piperacillin, in febrile patients with treatment-induced neutropenia. Fifty patients were prospectively randomized to receive piperacillin plus gentamicin (PG), and 46 were randomized to receive piperacillin plus ciprofloxacin (PC). The groups were similar in age, sex, diagnosis, duration of neutropenia, and incidence of positive cultures. The two antibiotic regimens were associated with comparable rates of defervescence in the patients with Gram-positive bacteremia. In the patients with Gram-negative bacteremia and those with negative cultures, however, defervescence was more prompt in the PC group. In particular, 27% of the culture-negative patients on PC, compared to only 5% of those on PG, defervesced within 72 hr (P = 0.015). Because of the more prompt defervescence in the PC group, amphotericin B was used less frequently; 78% of the patients on PG compared with only 56% of those on PC were started on amphotericin B (P J Biomed Mater Res, 41, = 0.025). PC is an effective alternative to the more traditional PG for treatment of febrile neutropenic hosts who have not been given prophylactic quinolones. More important, PC appears to hasten defervescence compared with PG, especially in culture-negative patients and those with Gram-negative bacteremia, and may decrease the necessity of additional antimicrobial agents such as amphotericin B. 1998. Am. J. Hematol. 58: 293–297, 1998. © 1998 Wiley-Liss, Inc.  相似文献   

4.
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.  相似文献   

5.
Gram-positive breakthrough infections pose a major drawback to the use of quinolones for antibacterial prophylaxis in neutropenic patients. Levofloxacin offers the advantage of an augmented Gram-positive spectrum and may potentially overcome this problem. In an open-label, clinical pilot study, we investigated the effects on throat and bowel microflora and pharmacokinetics of a once-daily oral dose of 500 mg levofloxacin, during neutropenia in 20 patients with haematological malignancies. Gram-negative bowel flora and Staphylococcus aureus were successfully eradicated. No Gram-negative infections occurred. Minimal inhibitory concentration values for viridans group (VG) streptococci tended to increase, in four patients over 8 mg/l, indicating resistance to levofloxacin. Four patients developed blood-stream infections with levofloxacin-resistant Gram-positive cocci. No significant changes in numbers of anaerobic microorganisms were observed. Pharmacokinetic parameters of levofloxacin, including the maximum serum concentration (C(max)), time to C(max) (T(max)), area under the concentration-time curve (AUC), volume of distribution at steady state (V(ss)/F) and clearance (CL/F) were not statistically different at first dose and during neutropenia. In conclusion, levofloxacin eradicates Gram-negative microorganisms and S. aureus and spares the anaerobic flora. Its pharmacokinetic profile is unaltered during neutropenia. However, prolonged administration of levofloxacin as antibacterial prophylaxis may be hampered by the emergence of levofloxacin-resistant VG streptococci.  相似文献   

6.
Viridans streptococci were the most common cause of bacteremia in 61 consecutive myeloablative allogeneic hematopoietic stem cell transplant (HSCT) recipients, occurring in 19 of 31 bacteremic patients (61%) during the period of post-transplant neutropenia. Seven of the 19 had more than one viridans streptococcus in the same blood culture. Twenty isolates from 15 patients were Streptococcus mitis. Most viridans streptococci were resistant to norfloxacin, used routinely for prophylaxis. Comparison of the 19 patients with viridans streptococcal bacteremia with a contemporaneous group of 23 allogeneic HSCT recipients with fever and neutropenia but no identified focus of infection found that patients with viridans streptococcal bacteremia were more likely to have severe intraoral pathology while neutropenic (26% vs 0%) and slightly shorter interval between the last dental procedure and the onset of neutropenia (11 vs 14 days). Poor underlying dental health and the use of norfloxacin thus appear to predispose to viridans streptococcal bacteremia.  相似文献   

7.
The incidence of Gram-negative bacteremia has increased in hematopoietic stem cell transplant (HSCT) recipients. We prospectively collected data from 13 Brazilian HSCT centers to characterize the epidemiology of bacteremia occurring early post transplant, and to identify factors associated with infection due to multi-drug-resistant (MDR) Gram-negative isolates. MDR was defined as an isolate with resistance to at least two of the following: third- or fourth-generation cephalosporins, carbapenems or piperacillin-tazobactam. Among 411 HSCT, fever occurred in 333, and 91 developed bacteremia (118 isolates): 47% owing to Gram-positive, 37% owing to Gram-negative, and 16% caused by Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa (22%), Klebsiella pneumoniae (19%) and Escherichia coli (17%) accounted for the majority of Gram-negative isolates, and 37% were MDR. These isolates were recovered from 20 patients, representing 5% of all 411 HSCT and 22% of the episodes with bacteremia. By multivariate analysis, treatment with third-generation cephalosporins (odds ratio (OR) 10.65, 95% confidence interval (CI) 3.75-30.27) and being at one of the hospitals (OR 9.47, 95% CI 2.60-34.40) were associated with infection due to MDR Gram-negative isolates. These findings may have important clinical implications in the decision of giving prophylaxis and selecting the empiric antibiotic regimen.  相似文献   

8.
Australian guidelines for neutropenic fever recommend piperacillin/tazobactam (PIP‐TAZ) or cefepime for first‐line empiric treatment of neutropenic fever. We compared outcomes among haematology patients before and after changing our first‐line neutropenic fever treatment from imipenem to PIP‐TAZ. Forty‐five patients received imipenem and 60 PIP‐TAZ. Despite a higher rate of antibiotic modification in the PIP‐TAZ cohort, treatment success and time to defervescence were similar, with a trend towards fewer Clostridium difficile infections in the PIP‐TAZ cohort.  相似文献   

9.
Antibiotic rotation and development of gram-negative antibiotic resistance   总被引:5,自引:0,他引:5  
To attain a better understanding of antibiotic cycling and its effects on the epidemiology of antibiotic resistance in gram-negative microorganisms, two different antibiotic classes (quinolone and beta-lactam) were cycled during four 4-month periods in a surgical intensive care unit. Respiratory aspirates and rectal swabs were obtained and DNA fingerprinting was performed. Primary endpoint of the study was the acquisition rate with gram-negative bacteria resistant to the antibiotic of choice during each cycle. Secondary endpoints were changes in endemic prevalence of resistant bacteria and the relative importance of cross-transmission. In all, 388 patients were included and 2,520 cultures analyzed. Adherence to antibiotic protocol was 96%. Overall antibiotic use increased with 24%. Acquisition rates with resistant bacteria were highest during levofloxacin exposure (relative risk [RR] 3.2; 95% confidence interval [CI]: 1.4-7.1) and piperacillin/tazobactam exposure (RR 2.4; 95% CI 1.2-4.8). The relative importance of cross-transmission decreased during the study. For individual patients, treatment with levofloxacin was the only independent risk factor for acquisition of levofloxacin-resistant bacteria (hazard ratio 12.6; 95% CI 3.8-41.6). Potential for selection of antibiotic-resistant gram-negative bacteria during periods of homogeneous exposure increased from cefpirome to piperacillin/tazobactam to levofloxacin. Cycling of homogeneous antibiotic exposure is unlikely to control the emergence of gram-negative antimicrobial resistance in intensive care units.  相似文献   

10.
Abstract: Serum endotoxin, interleukin-6 (IL-6) and C-reactive protein (CRP) were serially determined in 26 patients with hematological malignancies and chemotherapy-induced neutropenia who developed fever. Endotoxin in serum was detected in 69% of the patients, with the highest values being recorded in patients with gram-negative (Gr-) bacteremia. High levels of IL-6 were found after start of fever, and in 6/9 patients with Gr- bacteremia levels exceeded 200 ng/l in samples drawn within the first 72 hours. However, only in 2/17 patients with gram-positive bacteremias and blood culture-negative fever episodes did IL-6 exceed this concentration (p<0.05). High CRP values (exceeding 100 mg/l) did not discriminate between Gr- and non-Gr- episodes (7/9 versus 10/17, respectively). In patients with fever at day 3–5 (n = 15), IL-6 values > 100 ng/l were associated with fever continuing for more than 7 days after start of the episode; contrarily, CRP values did not indicate the persistence of fever. Determination of IL-6 may be a better test than CRP in monitoring the acute response to infection in the neutropenic patient. A combination of high endotoxin and IL-6 values may indicate a Gr- bacteremia. This could have therapeutic implications before results of blood cultures are obtained.  相似文献   

11.
The effect of an extensive prophylactic antimicrobial regimen was prospectively assessed in 126 patients after high-dose chemotherapy and autologous PBSC. They received ciprofloxacin (500 mg/12 h), acyclovir (200 mg/6 h), and itraconazole (200 mg/12 h) orally until neutrophil recovery. Febrile patients received i.v. imipenem (500 mg/6 h) to which vancomycin and amikacin were added if fever persisted for 2-3 and 5 days, respectively. Amphotericin B lipid complex was further given on day 7 or 8 of fever. Median times for a neutrophil count of >0.5 x 10(9)/l and a platelet count of >20 x 10(9)/l were 9 and 11 days. Severe neutropenia (<0.1 x 10(9)/l) lasted for a median of 5 days in which 72% of febrile episodes and 50% of cases of bacteremia occurred. Gram-positive bacteria were isolated in 30 of 40 episodes of bacteremia, 25 of which were caused by Staphylococcus epidermidis. Clinical foci were the intravascular catheter in 35 cases, respiratory infection in 11, cellulitis in two, anal abscess in one, and neutropenic enterocolitis in one. The high incidence of febrile episodes (94%) and bacteremias (31%) may be due to the lack of efficacy of antimicrobial prophylaxis and the persistence of a 5-day period of severe neutropenia.  相似文献   

12.
Three cases of viridans group streptococcal bacteremia in 2 children with brain tumours and in 1 with autoimmune neutropenia are presented. All children were neutropenic. The 2 patients with malignancy also had mucositis. The isolated strains of viridans group streptococci showed considerable resistance to antibiotics. All patients were empirically treated with third generation cephalosporins and amikacin, before antibiotic sensitivities were available and recovered without complications. Viridans group streptococcal bacteremia should be suspected in neutropenic children, especially in the presence of mucositis. Prospective, randomized clinical trials of mouth antiseptics are needed to clarify the usefulness, if any, of such measures in the reduction of viridans group streptococcal bacteremia in this group of patients.  相似文献   

13.
We performed a retrospective cohort study to measure the impact of vancomycin resistance on clinical outcome for 83 episodes of enterococcal bloodstream infection (BSI; 22 with vancomycin-resistant enterococci [VRE] and 61 with vancomycin-susceptible enterococci [VSE]) in 77 patients with neutropenia. Cox proportional hazards models showed that vancomycin resistance was an independent predictor of mortality, after controlling for severity of illness, enterococcal species, gram-negative copathogens, sex, race, duration of neutropenia before bacteremia, and early administration of active antibiotics. This effect was evident only > or =10 days after the onset of bacteremia (P=.0263; hazard ratio [HR], 4.969) but not after adjustment for duration of bacteremia. The median duration of bacteremia was 4.5 days for VRE BSI and <1 day for VSE BSI (P=.0001). The only independent predictor of bacteremia duration was vancomycin resistance (P=.0284; HR, 3.863). Vancomycin resistance is associated with increased mortality in patients with neutropenia, possibly because of prolonged duration of bacteremia.  相似文献   

14.
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.  相似文献   

15.
One hundred and fifty-seven patients undergoing high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) for hematopoietic malignancies and solid tumors were randomly assigned to receive (Group A) or not (Group B) prophylaxis with ciprofloxacin, orally, and vancomycin, intravenously. Prophylactic antibiotics were given from day 0 until resolution of neutropenia or the appearance of a febrile event. Furthermore, patients in both groups received once a day fluconazole, orally. The primary end-point of our study was the incidence of neutropenic febrile episodes attributed to infection. One hundred and twelve (71.3%) patients developed neutropenic fever, 50 (56.2%) in Group A and 62 (91.2%) in Group B (P < 0.001) with the majority (82%) of patients developing fever of unknown origin. Patients on prophylactic antibiotics had a significantly lower rate of bacteremias (5.6%) than did those randomized to no prophylaxis (29.4%) (P = 0.005) and, when developing neutropenic fever, they had a lower probability of response to first-line empirical antibiotics (P = 0.025). Prophylactic administration of ciprofloxacin and vancomycin reduced the incidence of neutropenic fever in patients receiving HDT with ASCT, however, without affecting the total interval of hospitalization, time to engraftment, or all-cause mortality. Therefore, our results do not support the use of antibiotic prophylaxis for patients undergoing HDT and ASCT.  相似文献   

16.
Patients previously diagnosed with invasive aspergillosis (IA) have been considered to be at risk for relapse of mycosis during subsequent hematopoietic transplant. Even with prophylactic measures, reactivation of the infection occurs in 29% of patients undergoing bone marrow transplantation (BMT). A period of neutropenia is one of the variables considered to be a risk factor for reactivation. Peripheral blood stem cell transplant (PBSCT) results in a shorter neutropenia period leading to a lower risk of fungal infection. A retrospective data analysis performed on patients undergoing autologous PBSCT for hematological malignancies in our unit showed that nine patients were diagnosed before transplantation with IA. All patients received only medical treatment during their primary infection. Medical prophylaxis was administered in seven of these patients, and two underwent transplantation without prophylaxis. All patients developed severe neutropenia after a myeloablative regimen. All but one had neutropenic fever, although the fever was controlled and no fungal complications occurred. All patients in this series achieved complete hematological engraftment without delay in granulocyte recovery (mean: 8.78 vs 9.76; p=0.58). No significant differences were observed in toxicities with regards to transplantation between patients previously diagnosed with IA and their controls. Recurrence of IA related to transplantation was avoided since no relapse of IA was demonstrated. This series of nine patients with a previous history of IA shows that medical treatment, secondary prophylaxis, and peripheral blood as a source of stem cells could be effective measures to avoid reactivation of previous aspergillosis during hematopoietic transplantation, although prospective randomized trials should still be performed to confirm these findings in a wider setting.  相似文献   

17.
Antibiotic therapy for gram-negative bacteremia.   总被引:3,自引:0,他引:3  
Although antibiotic therapy is the mainstay of therapy for gram-negative bacillary bacteremia, the amelioration of the underlying conditions, the correction of predisposing factors, the drainage of abscesses, the removal of infected foreign bodies, and adequate supportive care are also of paramount importance for curing the infection and should not be neglected. Beginning in the late 1960s, most of the clinical work on gram-negative infections has focused on the evaluation of new antibiotics. Numerous studies have shown that early, appropriate antibiotic treatment of gram-negative bacteremia significantly improved patients' outcomes and prevented the development of septic shock. Prescribing standard doses of antibiotics does not necessarily mean that therapeutic levels will be reached in all patients, and relapses of infections or breakthrough bacteremias can occur in patients with subinhibitory serum levels of antibiotics. The monitoring of serum concentrations of antibiotic is therefore recommended in critically ill septic patients. Whereas initial studies on the antibiotic treatment of gram-negative bacteremia were carried out in nonneutropenic patients, more recent clinical investigations have been performed almost exclusively in cancer patients with neutropenia. Studies conducted in the 1970s and 1980s among these patients have shown the following: (1) early empirical therapy reduced the mortality of gram-negative bacteremia; (2) therapy with a combination of two antibiotics, be it an extended spectrum penicillin plus an aminoglycoside or a third-generation cephalosporin, has significantly improved patients' outcomes; and (3) triple-drug combinations (i.e., a penicillin plus a cephalosporin plus an aminoglycoside) are not superior to combinations of beta-lactams and aminoglycosides. For the treatment of gram-negative bacteremia, clinicians today have a choice between well-established antibiotic combinations and broad-spectrum single-agent therapy with third-generation cephalosporins or carbapenem antibiotics. Although recent studies suggested that monotherapy could be as effective as combination therapy for the empirical treatment of fever in the neutropenic host, no definitive study has so far unquestionably demonstrated the equivalence of these treatments in patients with gram-negative bacteremias, especially those caused by P. aeruginosa, or in patients with adverse prognostic conditions, such as persistent and profound granulocytopenia. This literature should however be reviewed with great caution. Indeed, only a minority of studies have included a sufficient number of patients to confidently assess the impact of therapy on patients' outcomes. Obviously, small studies can have a significant risk of type II errors, that is, making false-negative conclusions.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

18.
High-dose etoposide (2 g/m(2)) plus G-CSF is a very effective regimen for peripheral blood progenitor cell (PBPC) mobilization. Unfortunately, neutropenia is common. The infectious complications associated with high-dose etoposide have not been previously described. After noting a high incidence of hospitalizations for neutropenic fever, we began a vigorous prophylactic antibiotic regimen for patients receiving high-dose etoposide plus G-CSF, attempting to reduce infectious complications. Ninety-eight patients underwent etoposide mobilization between December 1997 and June 2000. Three chronological patient groups received: (1) no specific antibiotic prophylaxis (n = 44); (2) vancomycin i.v., cefepime i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27); and (3) vancomycin i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27). The patients not receiving antibiotic prophylaxis had a 68% incidence of hospitalization for neutropenic fever. In the patients receiving prophylaxis, the incidence was reduced to 26% and 15% respectively, for an overall incidence of 20% (P < 0.001 for comparison between prophylaxed and unprophylaxed groups). We conclude that etoposide mobilization is associated with a significant incidence of neutropenic fever, which can be substantially reduced by a vigorous antimicrobial prophylactic program.  相似文献   

19.
Bacteremia is the most frequent infectious complication during neutropenia in patients receiving autologous hematopoietic stem cell transplantation (ASCT). The objective of this study was to analyze the incidence, characteristics, risk factors, and outcome of bacteremia during the early period after ASCT. A total of 720 patients undergoing ASCT in two observational prospective consecutive multicenter studies of the Programa Español para el Tratamiento de las Hemopatías group were analyzed. Bacteremia occurred in 20 % of patients. Coagulase-negative Staphylococcus was the most frequent (66 %) among the gram-positive agents and Escherichia coli (49 %) among the gram-negative agents. Multivariate analysis showed that the length of neutropenia <1?×?109/L (more than 9 days) [relative risk (RR) of 2.6, p?<?0.001] was the sole risk factor for overall bacteremia. We identified the length of neutropenia <1?×?109/L (more than 9 days) (RR 4.98, p?<?0.001) and the use of prophylactic fluoroquinolones (RR 0.46, p?<?0.01) as specific risk factors for gram-negative bacteremia. Risk factors for gram-positive bacteremia were the use of total parenteral nutrition (RR 1.92, p?<?0.01) and deep neutropenia (<0.1?×?109/L), with duration over 5 days (RR 1.67, p?<?0.027). Bacteremia showed an increased morbidity with no impact on neither overall nor infectious related mortality. The identification of such risk factors may be helpful to implement prophylactic and therapeutic risk-adapted strategies to reduce the incidence of bacteremia in ASCT.  相似文献   

20.
We report a case of bacteremia due to Abiotrophia species in a patient with neutropenic fever and cancer who was receiving levofloxacin prophylaxis, followed by empirical therapy with cefepime; the organism was resistant to both antibiotics. We provide susceptibility data on 20 additional bloodstream isolates of Abiotrophia species.  相似文献   

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