Incidence Of Gram-negative Bacteremia Research Articles

A novel prognostic model for malignant patients with Gram-negative bacteremia based on real-world research

Gram-negative bacteremia (GNB) is a common complication in malignant patients. Identifying risk factors and developing a prognostic model for GNB might improve the survival rate. In this observational and real-world study, we retrospectively analyzed the risk factors and outcomes of GNB in malignant patients. Multivariable regression was used to identify risk factors for the incidence of GNB, while Cox regression analysis was performed to identify significant prognostic factors. A prognostic model was constructed based on Cox regression analysis and presented on a nomogram. ROC curves, calibration plots, and Kaplan–Meier analysis were used to estimate the model. It comprised 1004 malignant patients with Bloodstream infection (BSI) in the study cohort, 65.7% (N = 660) acquired GNB. Multivariate analysis showed gynecologic cancer, hepatobiliary cancer, and genitourinary cancer were independent risk factors related to the incidence of GNB. Cox regression analysis raised that shock, admission to ICU before infection, pulmonary infection, higher lymphocyte counts, and lower platelet counts were independent risk factors for overall survival (OS). The OS was significantly different between the two groups classified by optimal cut-off value (log-rank, p < 0.001). Above all, a nomogram was created based on the prognostic model, which was presented on a website freely. This real-world study was concentrated on the malignant patients with GNB and proved that shock, admission to ICU before infection, pulmonary infection, higher lymphocyte counts, and lower platelet counts were related to the death of these patients. And a prognostic model was constructed to estimate the risk score of mortality, further to reduce the risk of death.

Febrile Neutropenia and Bacteremia after High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation in Patients Treated Inpatient Versus Outpatient

<h3>Introduction</h3> Multiple myeloma (MM) is the most common indication for high dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT). In addition, patients with immunoglobulin light-chain amyloidosis (AL), a related plasma cell disorder, often benefit from ASCT. Objectives: We aimed to compare baseline demographics, peri-transplant mortality, and the incidence of febrile neutropenia and bacteremia between an outpatient transplant cohort at one institution and an inpatient cohort at a second institution. <h3>Methods</h3> We performed a two-center retrospective chart review of all patients with plasma cell disorders undergoing ASCT between January 2014 and December 2018. All patients at transplant center A. were managed in the outpatient setting unless admission was necessary for febrile neutropenia, gastrointestinal toxicity, cardiac complications, or other adverse events. All patients at transplant center B were managed in the inpatient setting from conditioning regimen to engraftment post transplant. <h3>Results</h3> A total of 183 patients were included (103 outpatients vs 80 inpatients). There were no significant demographic differences between cohorts [Table 1]. The outpatient cohort (transplant center A) had a higher proportion of patients with AL amyloidosis (61% vs 38%), and a higher proportion of patients who received full high-dose melphalan at 200 mg/m2. Within the outpatient cohort, 48/103 (47%) patients were admitted for febrile neutropenia and 39/103 (38%) required admission for other reasons post-transplant. There were no differences in the incidence of febrile neutropenia or peritransplant mortality between cohorts [Table 1]. However, the incidence of bacteremia was higher in the outpatient cohort (23.3% vs 8.8%, p <0.01) with a high burden of gram negative bacteremia [Table 2]. Gastrointestinal toxicity of any grade occurred in a higher proportion of patients in the outpatient cohort (97% versus 79%). <h3>Conclusion</h3> In this contemporary two-center cohort of patients undergoing ASCT, there is no difference in 100-day mortality or incidence of febrile neutropenia between inpatient versus outpatient protocols. In addition, we demonstrate that outpatient transplant is a safe option for patients with AL amyloidosis. Prior studies comparing inpatient versus outpatient ASCT have been single-center studies, in which younger patients or those with fewer comorbidities were selected for outpatient transplant. The increased incidence of gram negative bacteremia in the outpatient cohort is in keeping with at least one prior single-center study, and is associated with a higher incidence of regimen-related gastrointestinal toxicity. Ongoing analysis will explore the impact of induction therapy prior to ASCT and gastrointestinal toxicity grading (correlated with melphalan dosing) on the incidence of bacteremia.

1018. Prevalence of Bacteremia/Fungemia and Pneumonia in Remission Induction Chemotherapy for Adult Acute Myeloid Leukemia From 1987 to 2005: Japan Adult Leukemia Study Group (JALSG)

BackgroundRemission induction (RI) chemotherapy for acute myeloid leukemia (AML) is one of the most intensive chemotherapy available. Antibiotic prophylaxis and prompt treatment for infectious complications during RI chemotherapy play a major role in supportive care.MethodsWe retrospectively analyzed the infectious complications associated with RI chemotherapy listed in the Japan Adult Leukemia Study Group AML201 protocol, a nationwide study of de novo AMLs, conducted between 2001 and 2005 in Japan. Of the 1,057 cases initially included in the AML201 study, 980 cases with data on infectious complications during RI chemotherapy were analyzed. The incidences of infectious complications and the causative pathogens were compared with previous studies [(period A) 1987–1991, 577 cases; (B) 1992–1995, 669 cases; (C) 1995–1997, 531 cases; (D) 1997–2001, 808 cases; (E) 2001–2005, 980 cases].ResultsIn study period E, the causative pathogens of bacteremia/fungemia were Staphylococcus epidermidis (20.9%), S. aureus (11.6%), Streptococcus sp. (14.0%), and other Gram-positive bacteria (18.6%); P. aeruginosa (12.8%) and other Gram-negative bacteria (10.5%); and fungi (9.3%). Pathogens causing pulmonary infections were Aspergillus sp.(15.8%), P. aeruginosa (7.9%), and other Gram-negative bacteria (6.9%) and Gram-positive bacteria (3.0%). Pulmonary aspergillosis was diagnosed mainly using serological test. The prevalence of bacteremia/fungemia was reported in 11.8%, 9.4%, 8.7%, 9.2%, and 8.3% of cases and pulmonary infections were reported in 24.6%, 16.9%, 13.9%, 12.9%, and 10.3% of cases in the study periods A, B, C, D, and E, respectively. The incidence of Gram-negative bacteremia was significantly lower in period E compared with the periods A, B, and C (2.0% vs. 4.9%, 3.7%, and 3.4%, respectively).ConclusionThe prevalence of Gram-positive bacteremia and pulmonary aspergillosis was higher in period E than in the periods A–D. This trend was possibly due to the wide use of fluoroquinolone prophylaxis in neutropenic patients and high performance of the serological test for aspergillosis. Sufficient monitoring for Gram-positive bacterial infection and mold infection is therefore essential during RI chemotherapy for AML.Disclosures All authors: No reported disclosures.

The Effect Of Donor and Recipient Statin Treatment On Infections After Allogeneic Hematopoietic Cell Transplantation

Background Recent studies have reported that statin use is associated with improved outcomes in immunocompetent patients with bacterial sepsis and respiratory virus disease. We have reported previously that statin use in donors or recipients was associated with reduced risks of severe acute graft-versus-host disease (GVHD) or chronic GVHD, respectively, after allogeneic hematopoietic cell transplantation (HCT). In the present study, we analyzed the influence of donor and recipient statin use on the incidence of infections and infection-outcomes after allogeneic HCT. Patients and Methods A previously reported cohort of HCT recipients (BBMT 16:1463-6, 2010) was used for the analyses. The cohort included 1206 allogeneic HCT recipients (no statin treatment: n=1130; statin treatment: n=76) transplanted between 2001 and 2008 at the Fred Hutchinson Cancer Research Center. Recipients were considered “statin-treated” when a statin was used to treat hyperlipidemia before and after HCT-conditioning. In addition, for all 567 sibling donors in the same cohort, the statin treatment status at the time of stem cell donation was assessed by review of medical records (no statin treatment: n=480, statin treatment: n=87; Blood 115:1288-95, 2010). The associations between statin use and risks of incident infections or infection-related mortality were evaluated using Cox proportional hazards models. Results Among 1206 HCT recipients, the following proportions experienced first infectious events within 100 days after HCT: bacteremia, 23% (n=275); CMV reactivation, 23% (n=277); respiratory viral infection with upper and/or lower respiratory tract involvement, 8.0% (n=97), and with only lower respiratory tract involvement (LRI), 1.8% (n=22). Within 1 year after HCT, 13% (n=153) developed invasive fungal infections and 3.7% (n=45) developed CMV disease. The overall incidences of bacteremia, invasive fungal infection, CMV reactivation, CMV disease, and LRI were not impacted by recipient or donor statin use. Recipient statin-use, however, was associated with a significantly increased cumulative incidence of gram-negative bacteremia (adjusted HR 2.15 [95% CI, 1.1-4.1], p=0.02), an association not observed with donor statin use. The risk of 30-day mortality attributable to gram-negative bacteremia was not significantly affected by recipient or donor statin use. Finally, the risk of respiratory viral infections was increased in recipients transplanted from statin-treated donors compared with those transplanted from donors not treated with a statin (adjusted HR 2.7 [95% CI, 1.3-5.6], p=0.01). There were no progressions to LRI among recipients transplanted from statin-treated donors (0% vs. 15%, p=0.15). Conclusions Recipient or donor statin use did not alter incidence of most infections after allogeneic HCT. However, while recipient statin use was associated with an increased risk of gram-negative bacteremia, donor statin use was associated with an increased risk of recipient respiratory viral infections without affecting mortality or progression to LRI. The mechanisms underlying these associations remain unknown. Validation of the findings in other large cohorts and, ultimately, randomized trials are needed. Disclosures: Boeckh: Merck: Consultancy, Research Funding.

Seasonal variation in health care-associated bloodstream infection: Increase in the incidence of gram-negative bacteremia in nonhospitalized patients during summer

Recent research has suggested that episodes of gram-negative (GN) bloodstream infection (BSI) are more common in the population during summer months. Our objective was to determine if the same phenomenon could be observed in patients with health care-associated (HCA) BSI, and if so, whether a summer peak was less apparent in patients accommodated in a climate-controlled hospital environment. Data from episodes of HCA BSI spanning an 11-year period were analyzed. To test for seasonal variation in HCA BSI among hospitalized and nonhospitalized patients, and between GN and gram-positive organisms, the χ(2) goodness-of-fit test was used. There were 440 episodes of HCA GN BSI of which 259 (59%) occurred in inpatients and 181 (41%) occurred in noninpatients. A significant increase in the frequency of HCA GN BSI was observed in nonhospitalized patients during the summer months (P = .03) but not in climate-controlled hospitalized patients. The most common source of infection in these patents was an intravascular device (38%). We found an increased incidence of GN HCA BSI during summer that was not apparent in our inpatient cohort. The cause is unknown. It might be prudent to advise patients at risk of BSI (eg, those receiving intravascular infusions) to minimize exposure to high environmental temperature and to educate on possible behavioral factors that may increase risk.

Gram-negative bacteremia in neutropenic patients with hematologic disorders. Experiences with prophylactic use of fluoroquinolones

Gram-negative bacteremia remains a severe complication of neutropenia with a high mortality rate. For high-risk patients prophylactic use of fluoroquinolones is recommended as a preventive strategy. To study the effect of fluoroquinolone prophylaxis on Gram-negative bacteremia. In the retrospective survey Gram-negative bacteremic episodes occurring in a centre for hematology and stem cell transplantation were studied. Data from the year before and after instituting prophylaxis were compared with regard to the incidence of blood stream infections, spectrum of pathogens, rate of fluoroquinolone resistance and all cause mortality of affected patient population. Only a slight decrease in the incidence of Gram-negative bacteremia was seen (ARR: 0.024) after the introduction of fluoroquinolone prophylaxis. Spectrum of pathogens remained unchanged. However, the proportion of fluoroquinolone resistant Gram-negative isolates increased markedly (from 24% to 59%, p = 0.001), especially fluoroquinolone resistant E. coli strains became more prevalent (from 16% to 75%, p<0.001). All cause mortality at 7 and 30 days remained the same or increased insignificantly. With the current epidemiological background none of the expected benefits from the fluoroquinolone prophylaxis could be proven, whereas, the rate of fluoroquinolone resistance increased markedly. A reconsideration of present prophylactic strategies is suggested.

Gram-negative bacteremia induces greater magnitude of inflammatory response than Gram-positive bacteremia

IntroductionBacteremia is recognized as a critical condition that influences the outcome of sepsis. Although large-scale surveillance studies of bacterial species causing bacteremia have been published, the pathophysiological differences in bacteremias with different causative bacterial species remain unclear. The objective of the present study is to investigate the differences in pathophysiology and the clinical course of bacteremia caused by different bacterial species.MethodsWe reviewed the medical records of all consecutive patients admitted to the general intensive care unit (ICU) of a university teaching hospital during the eight-year period since introduction of a rapid assay for interleukin (IL)-6 blood level to routine ICU practice in May 2000. White blood cell count, C-reactive protein (CRP), IL-6 blood level, and clinical course were compared among different pathogenic bacterial species.ResultsThe 259 eligible patients, as well as 515 eligible culture-positive blood samples collected from them, were included in this study. CRP, IL-6 blood level, and mortality were significantly higher in the septic shock group (n = 57) than in the sepsis group (n = 127) (P < 0.001). The 515 eligible culture-positive blood samples harbored a total of 593 isolates of microorganisms (Gram-positive, 407; Gram-negative, 176; fungi, 10). The incidence of Gram-negative bacteremia was significantly higher in the septic shock group than in the sepsis group (P < 0.001) and in the severe sepsis group (n = 75, P < 0.01). CRP and IL-6 blood level were significantly higher in Gram-negative bacteremia (n = 176) than in Gram-positive bacteremia (n = 407) (P < 0.001, <0.0005, respectively).ConclusionsThe incidence of Gram-negative bacteremia was significantly higher in bacteremic ICU patients with septic shock than in those with sepsis or severe sepsis. Furthermore, CRP and IL-6 levels were significantly higher in Gram-negative bacteremia than in Gram-positive bacteremia. These findings suggest that differences in host responses and virulence mechanisms of different pathogenic microorganisms should be considered in treatment of bacteremic patients, and that new countermeasures beyond conventional antimicrobial medications are urgently needed.

Epidemiology of bacteremia and factors associated with multi-drug-resistant gram-negative bacteremia in hematopoietic stem cell transplant recipients

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.

Gram-negative bacteraemia (GNB) after 428 unrelated donor bone marrow transplants (UD-BMT): risk factors, prophylaxis, therapy and outcome.

Gram-negative infection is an important cause of morbidity and mortality after unrelated donor-bone marrow transplantation (UD-BMT). We performed a retrospective case-control study to examine the risk factors, prophylaxis, therapy and outcome of Gram-negative bacteraemia (GNB) in 428 patients undergoing UD-BMT. The incidence of GNB was 3.6% in children and 19% in adults. Of the adults, 11% developed GNB >60 days post UD-BMT. Predisposing risk factors for GNB included 'high-risk' disease status, chronic graft-versus-host disease and use of systemic steroids. Fever, a raised C-reactive protein (CRP) and hypotension were common findings at presentation. Patients were routinely given prophylactic ciprofloxacin: resistance to this antibiotic was seen in 33% of isolates. We identified an age-matched control group undergoing UD-BMT over the same time period as the study group. Gram-positive bacteraemia was significantly more common in cases than controls. Mortality from GNB was 17% in children and 24% in adults. We conclude that GNB is a common complication of UD-BMT with a high associated mortality. Patients should be educated further to present rapidly with symptoms suggestive of infection.

Outbreaks of infection and/or pyrogenic reactions in dialysis patients.

These dialysis-related outbreaks demonstrate the ongoing potential for infection-related morbidity and mortality among dialysis patients. Many of these outbreaks could have been prevented by adequate water treatment, proper disinfection of water systems and dialysis machines, adherence to recommended reprocessing protocols in centers reusing dialyzers, and more stringent quality control monitoring. Finally, these outbreaks highlight the importance of active surveillance for adverse events among dialysis patients. The incidence of gram-negative bacteremia, pyrogenic reactions, and peritonitis should be monitored over time and any increase in incidence investigated.

Oral Care with Vancomycin Paste for Reduction in Incidence of α-Hemolytic Streptococcal Sepsis

alpha-Hemolytic streptococcal (AHS) sepsis is increasing in oncology patients receiving myelosuppressive chemotherapy. In response to a high rate of AHS sepsis in this population at our institution, an oral care protocol was instituted, including vancomycin 0.5% in flavored methylcellulose (vanc paste) applied orally t.i.d. at the oncologists' discretion. A retrospective cohort study of 239 neutropenic episodes among 42 children receiving myelosuppressive chemotherapy between 1988 and 1991 compared the incidence of septicemia based on the prophylactic use of vanc paste. A total of 236 consecutive neutropenic episodes were evaluable, 121 with vanc paste and 115 without. AHS sepsis occurred in one child using vanc paste and in six children not using vanc paste (p = 0.06). Excluding staph-only positive blood cultures, which would not be reduced with a topical oral antibiotic drug, there were 6 and 13 positive blood cultures in the vanc-paste and nonvanc-paste patients, respectively (p = 0.09). There was no increase in incidence of gram-negative bacteremia among vanc-paste recipients. Vancomycin resistance was not encountered. This analysis suggests that vanc paste effectively reduces AHS sepsis, does not increase gram-negative bacteremia, and is not associated with vancomycin resistance. A multicentered, placebo-controlled, double-blind study is currently planned.

Incidence of Gram‐negative bacteraemia in sepsis syndrome Implications for immunotherapy

The incidence of Gram-negative bacteraemia in 100 patients with sepsis syndrome receiving antibiotics, and admitted to the Intensive Therapy Unit, was only 12%. If endotoxin antibody is only effective in bacteraemic patients and these results are confirmed, there would be little indication for its use in our Intensive Therapy Unit.

Gentamicin Resistance Among Gram-negative Bacillary Blood Isolates in a Hospital With Long-term Use of Gentamicin

Between 1977 and 1985, gentamicin was the only formulary aminoglycoside at the Buffalo Veterans Administration Medical Center. During this time, there was a significant increase in the amount of gentamicin purchased. Amikacin represented 11% or less of the total aminoglycoside purchased in the same period, but purchases of this agent also significantly increased. Because of this long-term use of gentamicin, a retrospective analysis of gentamicin resistance among gram-negative bacillary blood isolates was performed. The results of this review revealed no significant change in the overall incidence of gram-negative bacteremia; approximately 75% of these bacteremic episodes were hospital acquired. The mean yearly gentamicin-resistance rate of gram-negative blood isolates was 13.2% (range, 6% to 18%) with no significant change in the rate for the period reviewed. However, for certain strains there were fluctuations in the percentage of resistance from year to year, suggesting that clusters of infections due to these organisms had occurred. Bacteremic infection due to resistant organisms was a major contributor to the overall level of gentamicin resistance among blood isolates. Amikacin resistance among gram-negative blood isolates was rare. In conclusion, despite the predominant use of gentamicin there was no change in the gentamicin resistance rate among gram-negative bacillary blood isolates during a nine-year period. The rate of gentamicin resistance among blood isolates appeared to be related to outbreaks/clusters of infections due to resistant strains rather than the frequency of use of gentamicin.

Radiation induced gram negative bacteremia and endotoxemia in rabbits: Modification by anti-lipopolysaccharide hyperimmune equine plasma

Lethal whole body irradiation damages the gut mucosa and leads to leakage of endotoxin or lipopolysaccharides (LPS) into the systemic circulation. Sixteen rabbits, irradiated with 900 rads 60Co, were randomly divided on day 4 into 2 groups, one of which received an intraperitoneal injection of normal saline (control) and the other (experimental) an equal volume of anti-LPS hyperimmune plasma. The time course of endotoxemia and bacteremia were determined for the duration of the experiment. While rabbits in both groups died within 13 days after irradiation, rabbits given saline died on average 2 days earlier, than rabbits given anti-LPS plasma. Plasma LPS concentrations rose to a small peak on day 2 prior to treatment. Thereafter plasma LPS in rabbits given saline increased forty fold by day 9. In contrast, in rabbits given anti-LPS plasma, LPS concentrations in the plasma remained within pretreatment limits (p 0.01). By day 12 after irradiation, plasma anti-LPS IgG had declined to 5.8% of pretreatment levels in rabbits given saline as compared to 46% in rabbits given anti-LPS plasma (p 0.005). Whilst both groups developed gram-positive bacteremia, rabbits given saline in addition also developed gram-negative bacteremia. No rabbits treated with Anti-LPS showed gram-negative bacteremia. Treatment with Anti-LPS plasma thus significantly protects radiated rabbits from the incidence of gram-negative bacteremia, development of high plasma LPS levels and hence endotoxemia, and prolongs survival to a certain extent.

Gram Negative Sepsis and Shock

In the modern hospital gram negative bacteremia and the associated condition of septic shock are common occurrences. In the United States the estimated incidence of gram negative bacteremia ranges from 71,000 to 330,000 cases annually. Fatalities attributed to this disease are between 18,000 and 132,000 each year. Sepsis is defined as a systemic disease caused by microorganisms or their products in the blood. Bacteremia is the presence of viable organisms in the circulation. Gram negative bacteremia in the critically ill patient is synonymous with gram negative sepsis. Septic shock is a clinical syndrome characterized by circulatory insufficiency and inadequate tissue perfusion. Septic shock is associated primarily although not exclusively with gram negative bacilli. Focus is on predisposing factors, microbiology, pathophysiology, and the 4 components of therapy -- antibiotics, volume replacement, steroids, and surgical drainage. The underlying illness of the patient is the primary factor determining the outcome of an episode of gram negative bacteremia. Patients with a life threatening disorder have a very poor prognosis, while sepsis in a previously healthy person carries a good prognosis. The overall mortality in gram negative bacteremia is 25%. When septic shock develops, the mortality increases to 50-60%. Appropriate antibiotics that are synergistic against the infecting organism can decrease the mortality, but the overwhelming infleunce of host factors in predicting the outcome suggests that prevention and early treatment are the best means of decreasing mortality.

Antibiotics and Gram-Negative Bacteremia-Reply

In Reply.— I welcome the thoughtful comments of Dr McGowan on the data that I presented in the March 31 communication (231:1361,1975) and would like to elaborate further on some of these points. Dr McGowan implies that the emergence of the Gram-negative organisms Klebsiella, Enterobacter , and Serratia as causative agents in bacteremia since the 1930s is the result of the introduction and use of penicillin and the broad-spectrum antibiotics. This is true only in the sense that these antibiotics have been successful in treating the Gram-positive infections that previously were the sources of bacteremia and in keeping alive people who, when older, become more susceptible to Gram-negative bacteremia. 1 Other factors operative in the hospital, such as more debilitated patients, imperfect sterile technique, wider use of immunosuppressant agents, and greater use of respiratory, vascular, and urinary instrumentation are unquestionably contributing substantially to the increased incidence of Gram-negative bacteremia. 2-4 Some