Cases Of Gram-negative Bacteremia Research Articles

52. Development and Implementation of a Short Duration of Antibiotic Therapy Algorithm for Uncomplicated Gram-Negative Bacteremia

BackgroundRecent literature suggests no difference in clinical outcomes between short (7 days) and prolonged course (14 days) antibiotic therapy for the treatment of uncomplicated Gram-negative bacteremia (GNB).MethodsThe objectives of the study were to develop and implement a treatment algorithm that identifies patients who are eligible for 7-day therapy for uncomplicated GNB and evaluate its impact on patient outcomes at The Johns Hopkins Hospital (JHH) in Baltimore. The algorithm was developed and implemented at JHH on 11/11/2019. From 11/11/2019 to 3/31/2020, the Infectious Diseases (ID) Pharmacy Resident and ID pharmacists reviewed cases of GNB on weekdays and contacted teams to provide algorithm-compliant treatment recommendations. To quantify the impact of the intervention on clinical outcomes, data from the same time period during the previous year (baseline) were collected and compared to those collected during the intervention. The primary outcome was duration of antibiotic therapy for GNB. Secondary outcomes included: duration of intravenous (IV) antibiotics, length of hospital stay (LOS), and recurrent bacteremia.ResultsA total of 345 patients with GNB were identified (142 baseline; 203 intervention) of which 59 and 55 patients met criteria for 7-day therapy, respectively. The Pitt bacteremia score (median 1), bacteremia source [urinary (43%), abdominal (23%)], and organisms [E. coli (48%) and Klebsiella spp. (33%)] were similar between the periods. More patients in the intervention period were treated for ≤8 days (60.0% vs. 37.3%; p=0.015), and the median duration of therapy was 2 days shorter (8 vs. 10 days; p=0.04). Median duration of IV antibiotic therapy (4 vs. 7 days; p=0.004) and median LOS (4 vs. 7 days; p=0.029) were also shorter in the intervention period. There were no differences in the rate of 30-day recurrent bacteremia between the periods (3.4% baseline vs. 1.8% intervention; p=0.60).ConclusionOur pharmacist-led intervention successfully shortened the duration of therapy, increased conversion from IV to PO therapy, and reduced LOS, without negatively impacting the number of patients with recurrent GNB.Disclosures All Authors: No reported disclosures

Characteristics of gram-negative bacteremia during febrile neutropenia among allogeneic hematopoietic stem cell transplant recipients on levofloxacin prophylaxis.

The aim of this study is to clarify the characteristics of gram-negative bacteremia (GNB), including extended-spectrum β-lactamase (ESBL)-producing pathogens, among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients on levofloxacin (LVFX) prophylaxis. A retrospective analysis on GNB at the first episode of febrile neutropenia (FN) was conducted among allo-HSCT recipients (age ≥ 20years) on 500mg/day of oral LVFX prophylaxis. Epidemiological and microbiological features of GNB were investigated and compared between the inappropriate and appropriate empiric therapy groups. In total, FN occurred in 414 allo-HSCT cases, and bacteremia at the first episode of FN occurred in 169 cases. Overall, 29 GNB cases were documented, and the causative organisms identified were Escherichia coli in 21 cases (including 10 ESBLs), Klebsiella pneumoniae in 2, Pseudomonas aeruginosa in 2, and other in 4. The crude 30-day mortality rate was not significantly different among cases of GNB (6.9%), gram-positive bacteremia (GPB) (7.1%), or non-bacteremia (5.4%; P = 0.78). Cefepime (CFPM) was administered in all cases in the inappropriate empiric therapy group, and all causative organisms were ESBL-producing E. coli (ESBL-EC). All patients in the inappropriate empiric therapy group had a low Pitt bacteremia score (≤ 2). Thirty-day mortality did not differ significantly between the inappropriate and appropriate empiric therapy groups (1/10 vs. 1/15, P = 0.61). In conclusion, GNB was not a significant cause of death. In LVFX breakthrough ESBL-EC bacteremia among allo-HSCT recipients, the administration of CFPM as empiric therapy did not lead to significantly poor prognosis. Empiric CFPM administration might be an acceptable strategy.

Predictive scoring models for persistent gram-negative bacteremia that reduce the need for follow-up blood cultures: a retrospective observational cohort study

BackgroundAlthough the risk factors for positive follow-up blood cultures (FUBCs) in gram-negative bacteremia (GNB) have not been investigated extensively, FUBC has been routinely carried out in many acute care hospitals. We attempted to identify the risk factors and develop a predictive scoring model for positive FUBC in GNB cases.MethodsAll adults with GNB in a tertiary care hospital were retrospectively identified during a 2-year period, and GNB cases were assigned to eradicable and non-eradicable groups based on whether removal of the source of infection was possible. We performed multivariate logistic analyses to identify risk factors for positive FUBC and built predictive scoring models accordingly.ResultsOut of 1473 GNB cases, FUBCs were carried out in 1268 cases, and the results were positive in 122 cases. In case of eradicable source of infection, we assigned points according to the coefficients from the multivariate logistic regression analysis: Extended spectrum beta-lactamase-producing microorganism (+ 1 point), catheter-related bloodstream infection (+ 1), unfavorable treatment response (+ 1), quick sequential organ failure assessment score of 2 points or more (+ 1), administration of effective antibiotics (− 1), and adequate source control (− 2). In case of non-eradicable source of infection, the assigned points were end-stage renal disease on hemodialysis (+ 1), unfavorable treatment response (+ 1), and the administration of effective antibiotics (− 2). The areas under the curves were 0.861 (95% confidence interval [95CI] 0.806–0.916) and 0.792 (95CI, 0.724–0.861), respectively. When we applied a cut-off of 0, the specificities and negative predictive values (NPVs) in the eradicable and non-eradicable sources of infection groups were 95.6/92.6% and 95.5/95.0%, respectively.ConclusionsFUBC is commonly carried out in GNB cases, but the rate of positive results is less than 10%. In our simple predictive scoring model, zero scores—which were easily achieved following the administration of effective antibiotics and/or adequate source control in both groups—had high NPVs. We expect that the model reported herein will reduce the necessity for FUBCs in GNB cases.

656. Prioritizing Gram-Negative Bacteremia (GNB) Cases for Rapid Detection by β-Lactam Resistance (BLR) and Patient Outcomes

BackgroundGNB is associated with significant morbidity and mortality. The availability of rapid diagnostic tests (RDTs) provides an opportunity to improve outcomes. Our goal was to review GNB and its empiric treatment at our center in order to devise rational approaches to diagnostic stewardship and use of RDTs.MethodsAll patients with GNB from 2010 to 2018 were evaluated. BLR was defined by 2019 CLSI breakpoints; phenotypes are shown in Table 1.ResultsA total of 2795 GNB cases were included (Table 2); 57% occurred within the first 24 hours of hospitalization and 29.3% in the ICU. The median length of stay (LOS) was 12 days; 17.2% of patients were re-admitted within 30 days. Fourteen- and 30-day mortality rates were 13.7% and 19.5%, respectively. Rates of death were higher (30 days; 26.3% vs. 17.1%; P < 0.001) and median LOS longer (17 vs. 11 days; P < 0.001) among patients with BLR compared with susceptible GNB. Thirty-day mortality rates were highest for CRE (30.1%) and BLR P. aeruginosa (BLR-Pa; 32.8%, Figure 1). 47.7% of BLR GNB were non-CRE/ESBL, which demonstrated higher mortality rates than CRE/ESBL (30 days; 27.6% vs. 21.2%; P = 0.048). Most common empiric regimens prescribed were piperacillin–tazobactam (TZP; 50.3%), cefepime (FEP; 24.2%), carbapenem (9.3%), or other agents (16.2%). 21.6% of GNB patients received inactive empiric treatment (IET). Empiric TZP (21.9%) was more likely to be inactive than FEP (17.5%; P = 0.05), but not a carbapenem (20.7%; P = NS). 57.6% of patients with inhibitor-resistant Enterobacteriaceae (IRE) received TZP empirically. Receipt of IET was associated with higher rates of death (30 days; 22.5% vs. 16.7, P = 0.03) and longer LOS (14 vs. 11 days; P < 0.001) than receipt of active ET. Rates of IET varied by pathogen (Figure 1).ConclusionIET is common against BLR GNB and associated with poor pt outcomes, highlighting the potential for RDTs and diagnostic stewardship teams (DSTs) to improve care. Genotypic RDTs detect most CRE/ESBL, but may miss nearly 50% of BLR GNB cases at our center. BLR-Pa and IRE are pathogens associated with prolonged LOS, and high rates of IET and death. These pathogens could be detected earlier by phenotypic RDTs and prioritized by DSTs to optimize early treatment regimens. Disclosures All authors: No reported disclosures.

116. Risk Factors and Clinical Outcomes of Carbapenem Non-Susceptible Gram-Negative Bacteremia in Patients with Acute Myelogenous Leukemia

BackgroundEarly administration of susceptible antibiotics is crucial in Gram-negative bacteremia (GNB), especially in immunocompromised patients. We aimed to explore risk factors and clinical outcomes of carbapenem non-susceptible (Carba-NS) GNB in patients with acute myelogenous leukemia (AML).MethodsCases of all GNB during induction or consolidation chemotherapy for AML in a 15-year period in a tertiary hospital were retrospectively reviewed. Independent risk factors for Carba-NS GNB were sought and its clinical outcomes were compared with those of carbapenem susceptible (Carba-S) GNB.ResultsAmong 485 GNB cases from 930 patients, 440 (91%) were Carba-S and 45 (9%) were Carba-NS GNB. Frequent Carba-NS isolates were Stenotrophomonas maltophilia (n = 23), Pseudomonas aeruginosa (n = 11), and Acinetobacter baumannii (n = 10). Independent risk factors for Carba-NS GNB were carbapenem use at the onset of GNB (aOR [95% CI], 78.6 [24.4–252.8]; P < 0.001), the isolation of imipenem-resistant A. baumannii in the prior 1 year (aOR [95% CI], 14.6 [2.7–79.9]; P = 0.002), time interval from chemotherapy to GNB ≥20 days (aOR [95% CI], 4.7 [1.7–13.1]; P = 0.003), and length of hospital stay ≥30 days (aOR [95% CI], 3.4 [1.3–9.1]; P = 0.013). Except breakthrough GNBs which occurred during carbapenem treatment, the frequency of Carba-NS GNB was 48% (19/40) in cases having ≥2 risk factors other than carbapenem use. 30-day overall mortality (Carba-NS, 36% vs. Carba-S, 6%; P < 0.001) and in-hospital mortality (Carba-NS, 47% vs. Carba-S, 9%; P < 0.001) were significantly higher in Carba-NS GNB.ConclusionCarba-NS GNB in AML patients was independently associated with the use of carbapenem, the past isolation of resistant organism, and late onset of GNB, and its clinical outcomes were poorer than those of Carba-S GNB. Carba-NS organisms should be considered for antibiotic selection in AML patients having these risk factors.Disclosures All authors: No reported disclosures.

Between Community and Hospital: Healthcare-Associated Gram-Negative Bacteremia among Hospitalized Patients

Healthcare-associated, community-acquired bacteremia is a subcategory of community-acquired bacteremia distinguished by recent exposure of the patient to the healthcare system before hospital admission. Our objective was to apply this category to a prospective cohort of hospitalized patients with gram-negative bacteremia to determine differences in the epidemiological characteristics, treatment, and outcome of community-acquired bacteremia; healthcare-associated, community-acquired bacteremia; and hospital-acquired bacteremia. A 6-month prospective cohort study. A 1,250-bed tertiary care hospital. Adults hospitalized with gram-negative bacteremia. Among 250 patients, 160 (64.0%) had bacteremia within 48 hours after admission; 132 (82.5%) of these were considered to have healthcare-associated, community-acquired bacteremia, according to previously published criteria. For patients with healthcare-associated, community-acquired bacteremia, compared with patients with community-acquired bacteremia, malignancies (59 [44.7%] of 132 patients vs 3 [10.7%] of 28 patients; P = .001), open wounds at admission (42 [31.8%] vs 3 [10.7%]; P = .02), and intravascular catheter-related infections (26 [19.7%] vs 0; P = .009) were more frequent and Escherichia coli as a causative agent was less frequent (16 [57.1%] vs 33 [25.0%]; P = .001). There was no difference between these 2 groups in inadequate empirical antibiotic treatment (36 [27.3%] vs 6 [21.4%]; P = .5) and hospital mortality (18 [13.6%] vs 2 [[7.1%]; P = .5). Compared with 90 patients with hospital-acquired bacteremia, patients with healthcare-associated, community-acquired bacteremia had a higher Charlson score (odds ratio [OR], 1.31 [95% confidence interval (CI), 1.14-1.49]) but were less likely to have lymphoma (OR, 0.07 [95% CI, 0.01-0.51]), neutropenia (OR, 0.21 [95% CI, 0.07-0.61]), a removable foreign body (OR, 0.08 [95% CI, 0.03-0.20]), or Klebsiella pneumoniae infection (OR, 0.26 [95% CI, 0.11-0.62]). Many cases of gram-negative bacteremia that occurred in hospitalized patients were healthcare associated. The patients differed in some aspects from patients with community-acquired bacteremia and from those with hospital-acquired bacteremia, but not in mortality.

Impact of Fluoroquinolone Prophylaxis on Reduced Infection‐Related Mortality among Patients with Neutropenia and Hematologic Malignancies

Fluoroquinolone prophylaxis during neutropenia in patients with cancer has been associated with decreased incidence of gram-negative bacteremia. Bacterial antimicrobial resistance is likely to cause a progressive lack of efficacy of fluoroquinolones, but no convincing evidence from clinicoepidemiologic observations has proved this hypothesis. This prospective observational study assessed the impact of discontinuing fluoroquinolone prophylaxis on the incidences of fever and bacteremia and on mortality among patients with neutropenia, after chemotherapy for hematologic malignancies. After a 12-month baseline period of levofloxacin prophylaxis, a period of discontinuation of fluoroquinolone prophylaxis was planned but was stopped prematurely after 9 neutropenic episodes over 3 weeks, because the mortality rate (33.3%) was higher than that with routine fluoroquinolone prophylaxis (2.9%) (odds ratio [OR], 16.6; 95% confidence interval [CI], 3.6-77.2). Fewer patients had gram-negative bacteremia during the baseline period (4.8%; n=15) than during the discontinuation period (44.4%; n=4) (OR, 16.9; 95% CI, 4.1-70.0). After levofloxacin therapy was reintroduced, the incidence of gram-negative bacteremia and the mortality rate were comparable to those during the first period. Escherichia coli isolated during the discontinuation period was susceptible to levofloxacin in vitro, whereas all E. coli isolates isolated during both prophylaxis periods were resistant. Bloodstream infections were caused by a single agent when the patient had received levofloxacin prophylaxis, whereas most cases of gram-negative bacteremia were polymicrobial after discontinuation. These findings suggest that, despite increasing rates of antimicrobial resistance, levofloxacin prophylaxis during neutropenia may have a beneficial impact on morbidity and infection-related mortality. Continued monitoring of the rate of gram-negative bacteremia is warranted for timely detection of the loss of efficacy of fluoroquinolone prophylaxis.

Review of the incidence and prognosis of Pseudomonas aeruginosa infections in cancer patients in the 1990s.

In an attempt to determine the actual relevance of Pseudomonas aeruginosa as a target of empiric antimicrobial first-line therapy in febrile cancer patients, 44 reports of clinical trials on antimicrobial treatment regimens and 53 reports on the epidemiology of microbiologically documented infections in cancer patients were reviewed. The incidence of infections due to Pseudomonas aeruginosa was 1-2.5% among all patients presenting with first fever during neutropenia, and 5-12% among patients with microbiologically documented infections. The proportion of Pseudomonas aeruginosa infections among cases of gram-negative bacteremia has not generally declined during the past 2 decades. There were marked local and regional differences regarding the incidence of documented Pseudomonas aeruginosa infections. No clear differences between neutropenic and non-neutropenic cancer patients, between patients with solid tumors and those with hematologic malignancies, or between inpatients and outpatients presenting with fever and neutropenia were detected with respect to the likelihood of Pseudomonas aeruginosa involvement. The mortality rate in patients with Pseudomonas aeruginosa bacteremia, particularly with polymicrobial bacteremia or bacteremic pneumonia with Pseudomonas aeruginosa involvement, is considerably high. The beneficial impact on mortality of an empiric antimicrobial treatment regimen with high antipseudomonal activity has not yet been demonstrated unequivocally. Additional factors such as the quality of intensive care management, effective second-line antimicrobial regimens, local resistance patterns, and patient-related cofactors are very likely to influence the outcome of Pseudomonas aeruginosa infections in cancer patients.

Neonatal gram-negative bacteremia.

A 22 months prospective study of neonatal gram-negative bacteremia was undertaken in a 15 bed NICU to find out the incidence and antibiotic resistance patterns. Clinically suspected 1326 cases of neonatal sepsis were studied during this period. More than 25% of the cases were microbiologically positive for sepsis. Among 230 (67.2%) cases of gram-negative bacteremia, the predominant isolates were Pseudomonas aeruginosa (38.3%), Klebsiella pneumoniae (30.4%), Escherichia coli (15.6%) and Acinetobacter sp. (7.8%). Fifty-nine per cent of the neonates were born in hospital while 41% were from community and referral cases. Lower respiratory tract infection, umbilical sepsis, central intravenous line infection and infection following invasive procedures were the most commonly identified sources of septicemia. Prematurity and low birth weight were the main underlying conditions in 60% of the neonates. Total mortality was 32%. Increased mortality was mainly associated with neutropenia, nosocomial infection and inappropriate antibiotic therapy. Resistance was increasingly noted against many antibiotics. The isolates were predominantly resistant to extended spectrum cephalosporins (25%-75%), piperacillin (68%-78%), and gentamicin (23%-69%). The commonest microorganisms causing gram-negative bacteremia were Pseudomonas aeruginosa followed by Klebsiella pneumoniae. The community-acquired bacteremia was mainly due to E. coli. The proportion of preterm and low birth weight babies was significantly high, and the major contributing factor in total mortality. Sensitivity to different antibiotics conclusively proved that a combination of ampicillin + sulbactam with amikacin or ampicillin + sulbactam with ciprofloxacin is most effective.

Pathophysiology and Management of Septic Shock

Septic shock occurs in about four of every 10 cases of Gram-negative bacteremia. Treatment must be prompt and aggressive and is directed toward assuring a clear airway and efficient pulmonary gas exchange, restoring adequate blood perfusion of vital tissues, and eradicating the infection. Aggressive fluid therapy given early may reverse the shock state. Cautious use of isoproterenol may be beneficial. As the initial antimicrobial agent, gentamicin has been shown to be superior. Use of phenoxybenzamine with fluid loading is still largely investigative.

Acute Leukemia and Infection

The clinical records of 78 patients with acute leukemia revealed that infection was the major single cause of death. Gram-negative bacteremia was responsible most often, although staphylococcal bacteremia was still a significant cause of death. Pneumonitis, bacteremia, and skin infections were the most common types of bacterial infections. An increase in the occurrence of infections with gram-negative organisms was noted. The source of most cases of gram-negative bacteremia was ulceration of the intestinal tract, although a number of patients had no source demonstrable. Serious fungal infections occurred in 14% (11) of patients studied. Most disseminated fungal infections were not diagnosed during life. Infections of all types increase with the duration of the disease and with the use of multiple therapeutic agents. Granulocytopenia appears to predispose to bacteremia and fungal infections.