Outcome and safety of colistin usage in pediatric cancer patients with carbapenem-resistant enterobacteriaceae bacteremia at children cancer hospital Egypt.

Background: Carbapenem resistant Enterobacteriacae (CRE) bloodstream infection (BSI) causes complicated infections, especially in immunocompromised patients. This study aimed to assess the renal toxicity and the efficacy of therapy with colistin in a cohort of pediatric cancer patients with BSIs due to CRE and sensitivity to colistin. Patients and Methods: This was an observational, prospective cohort study from May 2017 to October 2017 in Children's Cancer Hospital Egypt 57,357. All patients who had blood stream infections due to CRE receiving intravenous colistin were prospectively enrolled. We used a standardized case form to record patient characteristics, including age, sex, weight, underlying comorbidities, type of infection, causative organism, and antibiotic susceptibility testing. Daily doses, duration of colistin therapy, and co-administered antibiotics (aminoglycosides, vancomycin) were collected. Furthermore, clinical and microbiological responses to treatment were reported. The dosing schedule was based on a loading dose of 5 MU and a 5-MU twice-daily divided maintenance dose, titrated on renal function. Clinical cure, bacteriological clearance, and daily serum creatinine were recorded. Results: One hundred and forty-one Blood Stream infectious episodes mainly due to Klebsiella Species (pneumoniae and Oxytoca) (27%) and Escherichia coli (68%) were analyzed. All strains were susceptible to colistin with Minimum inhibitory concentration (MICs) of 0.19-1.5 mg/L. Patients were predominantly females (69%), with a mean age of 7 years. It was used as a combination therapy with carbapenems (69.2%) or aminoglycosides (80%). The median duration of treatment was 9 days (Range 1-50 days). Clinical and microbiological cure was observed in 110 cases (80%). Acute kidney injury developed during five treatment courses (4%) in which colistin was used in combination with amikacin. No renal replacement therapy was required and subsided within 7 days from colistin discontinuation. Conclusions: Our study showed that colistin had a high efficacy without significant renal toxicity in severe infections due to CRE Gram-negative bacteria.

Résumé Carbapenem-resistant Gram-negative (CRE) bloodstream infection (BSI) causes complicated infections, especially in immunocompromised patients .This study aimed to assess the renal toxicity and the efficacy of therapy with colistin in a cohort of pediatric cancer patients with BSIs due to CRE and sensitivity to colistin. colistin proved to be effective and safe in managing CRE in children with cancer Mots-clés: Colistin, cancer, children, and Carbapenem-Resistant Enterobacteriaceae.

Risk Factors for Nephrotoxicity in Methicillin-Resistant Staphylococcus aureus Bacteraemia: A Post Hoc Analysis of the CAMERA2 Trial.

BACKGROUND: Clinical risk factors for nephrotoxicity in Staphylococcus aureus bacteraemia remain largely undetermined, despite its common occurrence and clinical significance. In an international, multicentre, prospective clinical trial (CAMERA2), which compared standard therapy (vancomycin monotherapy) to combination therapy (adding an anti-staphylococcal beta-lactam) for methicillin-resistant S. aureus bacteraemia, significantly more people in the combination therapy arm experienced acute kidney injury compared with those in the monotherapy arm (23% vs 6%). OBJECTIVE: The aim of this post hoc analysis was to explore in greater depth the risk factors for acute kidney injury from the CAMERA2 trial. METHODS: Among participants of the CAMERA2 trial, demographic-related, infection-related and treatment-related risk factors were assessed for their relationship with acute kidney injury by univariable and multivariable logistic regression. Acute kidney injury was defined by a modified-KDIGO (Kidney Disease: Improving Global Outcomes) criteria (not including urinary output). RESULTS: Of the 266 participants included, age (p = 0.04), randomisation to combination therapy (p = 0.002), vancomycin area under the concentration-time curve (p = 0.03) and receipt of (flu)cloxacillin as the companion beta-lactam (p < 0.001) were significantly associated with acute kidney injury. On a multivariable analysis, concurrent use of (flu)cloxacillin increased the risk of acute kidney injury over four times compared with the use of cefazolin or no beta-lactam. The association of vancomycin area under the concentration-time curve with acute kidney injury also persisted in the multivariable model. CONCLUSIONS: For participants receiving vancomycin for S. aureus bacteraemia, use of (flu)cloxacillin and increased vancomycin area under the concentration-time curve were risk factors for acute kidney injury. These represent potentially modifiable risk factors for nephrotoxicity and highlight the importance of avoiding the use of concurrent nephrotoxins.

Cetuximab severe cutaneous toxicity a gateway for bacteremia: case report.

EGFR inhibitors used in the treatment of metastatic wild-RAS colorectal cancer in combination with chemotherapy are associated with dermatologic side events that are low grade in most cases. We report a case of severe cutaneous toxicity secondary to cetuximab associated with bacterial cellulitis. A 57-year-old woman with metastatic adenocarcinoma of the colon, receiving FOLFIRI and Cetuximab as a first-line treatment, presented with a severe erythematous rash and xerosis resistant to local treatment with moisturizing emollients. Few days later, the patient becomes febrile, and the rash becomes more diffuse with a sandpaper appearance on the face, neck, chest, and flexor creases with exfoliation of large areas of skin. A bacterial cellulitis secondary to a dermatologic severe toxicity of Cetuximab was suspected. The patient started on antibiotics and local treatment with good response. This is a life-threatening cutaneous toxicity of cetuximab with secondary bacterial infection. Early recognition of cutaneous side effects of EGFR inhibitors is important to prevent such type of toxicities.

Sodium Bicarbonate Locks May Be a Safe and Effective Alternative in Pediatric Intestinal Failure: A Pilot Study.

This was a retrospective study that compared outcomes in pediatric intestinal failure (IF) patients that were switched from ethanol lock therapy (ELT) to sodium bicarbonate lock therapy (SBLT). The primary outcome was rate of catheter-related blood stream infections (CRBSI). The secondary outcomes were number of hospitalizations, emergency room (ER) visits, central venous catheter (CVC)-related complications. In 4 patients, median rates of CRBSI were 2.77 (interquartile range [IQR] 0.6-5.6) on ELT versus 0 on SBLT per 1000 catheter days ( P = 0.17). The median rates of hospitalizations and ER visits for CVC-related complications were 6.1 (IQR 3.2-10.2) on ELT versus 0 on SBLT (IQR 0-0; P = 0.11) and 2.8 (IQR 2-3.6) on ELT versus 1.8 (IQR 0-3.7) on SBLT per 1000 catheter days ( P = 0.50), respectively. Rates of CVC-related complications were similar. No adverse events were reported. SBLT may be safe and effective for pediatric IF.

A Retrospective Analysis of Intravenous vs Oral Antibiotic Step-Down Therapy for the Treatment of Uncomplicated Streptococcal Bloodstream Infections.

Evidence supporting intravenous-to-oral (IV-to-PO) antibiotic deescalation for uncomplicated streptococcal bloodstream infections (BSIs) are limited. The objective of this study was to compare clinical outcomes of patients treated with IV-only versus IV-to-PO antibiotic therapy for uncomplicated streptococcal BSIs. This was a single-center, retrospective study of patients aged ≥18 years who received treatment for uncomplicated streptococcal BSIs from January 2017 to December 2019. Patients were excluded if they had a polymicrobial BSI, endocarditis, osteomyelitis, septic arthritis, or received antibiotic therapy for >14 days. The primary outcome was clinical failure, defined as persistent bacteremia, recurrence of bacteremia, or mortality at 30 days. Secondary outcomes included length of hospital stay, all-cause readmissions, development of Clostridioides difficile infection, and adverse antibiotic reactions. There were 98 patients who met the inclusion criteria: 51 patients in the IV-to-PO therapy group and 47 patients who received IV-only antibiotics. Streptococcus pneumoniae and beta-hemolytic streptococci were the most common pathogens. Patients received an average of 4.4 days of IV antibiotics before being stepped down to an oral agent. Hospital length of stay (6.3 vs 12.6 days; P < .001) and total antibiotic duration of therapy (11.8 vs 13.9 days; P = .002) were significantly shorter in patients receiving IV-to-PO therapy. There were no clinical failures observed in patients who received IV-to-PO antibiotic therapy. IV-to-PO step-down therapy for uncomplicated streptococcal BSIs was not associated with worse clinical outcomes compared to patients receiving IV-only antibiotic therapy.

Oral step-down therapy in patients with uncomplicated Staphylococcus aureus primary bacteremia and catheter-related bloodstream infections.

Patients with uncomplicated Staphylococcus aureus primary bacteremia and catheter-related bloodstream infection (CRBSI) should be treated for at least 14 days. However, evidence for oral step-down therapy is lacking in these patients. A retrospective cohort was identified from 2013 to 2018 in a 1,950-bed tertiary hospital. An oral antimicrobial therapy (OAT) group was defined as patients treated with oral antibiotics following less than 10 days of intravenous antimicrobial therapy (IAT). Treatment failure was defined as any case of recurrence or death within 90 days. A total of 103 patients were included in the analysis, including 32 patients treated with OAT. Rates of treatment failure were 3.2% and 12.7% in the OAT and IAT groups (P = 0.113). The length of hospital stay was shorter in the OAT group. OAT was not an independent risk factor for treatment failure. OAT may reduce the duration of hospitalization without adverse effects in these patients.

Impact of synbiotics treatment on bacteremia induced during neoadjuvant chemotherapy for esophageal cancer: A randomised controlled trial.

BACKGROUND & AIMS: To elucidate the impact of synbiotics on bacterial translocation and subsequent bacteremia during neoadjuvant chemotherapy for esophageal cancer. METHODS: Patients requiring neoadjuvant chemotherapy for esophageal cancer were randomized to receive synbiotics (synbiotics group) or no synbiotics (control group) during chemotherapy. Blood and fecal samples were taken before and after every chemotherapy cycle, and 1 day before surgery. Mesenteric lymph nodes (MLNs) were harvested at laparotomy (MLN-1) and after resection of the tumor (MLN-2). Bacteria in each sample were detected. Fecal microbiota and organic acid concentrations were also determined. The primary endpoint was the detection of bacteria in the blood samples, as well as the incidence of side effects during chemotherapy. The secondary endpoint was the detection rate of bacteria in the MLN samples collected during surgery. RESULTS: The study recruited a total of 42 patients (22 in the control group, 20 in the synbiotics group). Bacteria were detected in 16 of 101 blood samples in the control group, whereas those were detected only 2 of 100 blood samples in the synbiotics group (p < 0.001) during neoadjuvant chemotherapy. Additionally, bacteria were detected in 12 of 34 MLN samples in the control group, whereas no bacteria were detected in 38 MLN samples in the synbiotics group (p < 0.001). Suppression of bacterial translocation was at least partly associated with an increased fecal acetic acid concentration as well as a lowered fecal pH by synbiotics. The incidence rate of grade 3 gastrointestinal toxicity during chemotherapy was lower in the synbiotics group compared to the control group (8/22 vs. 1/20, p = 0.022). CONCLUSIONS: Neoadjuvant chemotherapy for esophageal cancer may induce bacterial translocation and subsequent bacteremia, which can be prevented by synbiotics administration. TRIAL REGISTRATION: The University Hospital Medical Information Network (http://www.umin.ac.jp; registration number ID 000007651).

Listeria monocytogenes Bacteremia During Isatuximab Therapy in a Patient with Multiple Myeloma.

An elderly patient with multiple myeloma (MM) was being treated with several regimens and developed a severe drug eruption, necessitating the use of atovaquone instead of trimethoprim-sulfamethoxazole for pneumocystis pneumonia (PCP) prophylaxis. For progressive MM, treatment with isatuximab, an anti-CD38 monoclonal antibody, was started. During the treatment, he developed Listeria monocytogenes bacteremia and recovered quickly with ampicillin administration. CD38 is closely related to the innate immune response against L. monocytogenes, and isatuximab may increase the risk of infection. Therefore, trimethoprim-sulfamethoxazole may be useful in the prevention of not only PCP but also L. monocytogenes infection.

Evaluation of Empiric Vancomycin for Fevers During High-dose Cytarabine Administration.

BACKGROUND: Cytarabine is a nucleoside analog used in chemotherapy regimens for the treatment of multiple hematologic malignancies. One of the known adverse effects of cytarabine, particularly in patients receiving high-dose cytarabine (HDAC), is drug-induced fever. Multiple studies have demonstrated an increased risk of viridans group streptococcal bacteremia in patients who have received HDAC. For this reason, our institution and several other institutions across the country routinely include vancomycin as empiric coverage for patients who develop fever during HDAC, due to concern for resistance to cephalosporin monotherapy. MATERIALS AND METHODS: Patient demographic, diagnosis, treatment, and outcome information was collected by electronic chart review for each HDAC infusion from 2007 to August 2018 at the University of Iowa Stead Family Children's Hospital. If fever was documented during or within 24 hours of HDAC, additional information was collected regarding patient outcome and diagnostic testing. RESULTS: Of 208 HDAC administrations documented, patients developed fevers during the course on 82 occasions (39.4%). A median of 3 blood cultures per febrile period were obtained from time of fever onset during HDAC administration through >24 hours afebrile. One blood culture was positive for an oral flora organism determined by the microbiology lab report to be a likely contaminant. There were no other positive blood cultures in non-neutropenic or neutropenic patients. CONCLUSION: Fever due to HDAC is relatively common but appears to frequently lack association with bacteremia during the time of HDAC administration. Broad-spectrum empiric antibiotic regimens including vancomycin may be unnecessary for these patients, particularly before they become neutropenic.

Type 1 interferon aggravates lipopolysaccharide-induced sepsis through upregulating Caspase-11 and Gasdermin D.

This study aimed to investigate the mechanism of type I interferon (IFN) in aggravating sepsis in bacterial infection, focusing on the roles of Caspase-11 (Casp11) and Gasdermin D (Gsdmd) in this process. Type I interferons, including IFNα and IFNß, were used to treat peritoneal macrophage harvested from wild-type or IFNα/ßR1 knockout (KO) mice, of which the levels of Casp11 and Gsdmd were monitored using real-time polymerase chain reaction (RT-PCR) and Western blot, the exposure to phosphatidylserine was monitored by flow cytometry, and tissue factor (TF) activation was assessed by RT-PCR and TF chromogenic assay. Endotoxemia in wild-type mice led to upregulation of Casp11 and Gsdmd in myeloid cells, which in contrast was attenuated in IFNα/ßR1 KO mice. IFNα or IFNß treatment led to dose-dependent upregulation of Casp11 and Gsdmd in peritoneal macrophages harvested from wild-type mice, but induced negligible changes in IFNα/ßR1 KO mice. Type I IFN promoted phosphatidylserine exposure in peritoneal macrophage from wild-type mice but not IFNα/ßR1 KO mice. Type I IFN induced insignificant changes of TF expression levels in both wild-type mice and IFNα/ßR1 KO mice, but the TF activity was markedly increased in wild-type mice after type I IFN treatment. Our data suggested that the upregulation of Casp11 and Gsdmd in myeloid cells and macrophages induced by endotoxemia was reliant on the expression of IFNα/ßR1. IFNα or IFNß treatment efficiently upregulated Casp11 and Gsdmd, phosphatidylserine exposure, and TF activity of macrophages. Therefore, type I IFN could aggravate sepsis through upregulating Casp11 and Gsdmd.

LPS induced PCT production via TLR-4/NF-кB passway:it is the difference of G-/G+ bacteremia rats.

Sepsis by Gram-negative bacteria infection leads to further increase in procalcitonin (PCT). Herein, we examined the expression of PCT after 24 h in rats by injecting Escherichia coli (E. coli) or Staphylococcus aureus (SA). Healthy male SD rats were divided into six groups (n = 8): (1) Control group: no treatment; (2) SA group: injected with 106CFU/ml SA suspension 0.1 ml in the tail vein; (3) SA and antibiotics group: injected with 106/ml SA bacterial suspension 0.1 ml and 4 mg/kg Cefotaxime sodium, q8h in the tail vein; (4) E. coli group: injected with 106CFU/ml E. coli suspension 0.1 ml in the tail vein; (5) E. coli and antibiotics group: injected with 106/ml E. coli bacterial suspension 0.1 ml and 4 mg/kg Cefotaxime sodium, q8h in the tail vein; and (6) Endotoxin group: injected with 5 mg/kg endotoxin in the tail vein. Expression of PCT was significantly increased in the E. coli, SA or endotoxin-induced bacteremia rats than in the control rats. Compared with SA, PCT was more significantly increased in E. coli rats. NF-κB changes were in line with PCT. Next, we investigated whether the expression of PCT decreased when TLR4 or NF-κB were inhibited after injecting E. coli in rats. A total of 40 healthy male SD rats were divided into five groups (n = 8): (1) Control group: no treatment; (2) E. coli group: injected with 106CFU/ml E. coli suspension 0.1 ml in the tail vein. (3) E. coli and PBS group: injected with 106CFU/ml E. coli suspension 0.1 ml and PBS 0.1 ml in the tail vein. (4) E. coli and TAK242: injected with 106CFU/ml E. coli suspension 0.1 ml and 3 mg/kg TAK242 in the tail vein. (5) E. coli and BAY-11-7082: injected with 106/ml E. coli suspension 0.1 ml and 25 mg/kg BAY-11-7082 in the tail vein. A marked increase of TLR4, NF-κB, LPS and PCT expression was observed in the lungs after E. coli induced bacteremia. Expressions of TLR4, NF-κB, and PCT proteins were decreased in the lungs at 24 h after injection of TAK-242 or BAY-11-7082. In summary, this study suggested that LPS is the key factor for differential expression of PCT between E. coli and SA bacteremia. E. coli induces PCT elevation via the TLR4/NF-κB pathway.

Citrulline as a biomarker of bacteraemia during induction treatment for childhood acute lymphoblastic leukaemia.

BACKGROUND: Systemic infections are a major cause of morbidity in children with acute lymphoblastic leukaemia (ALL). However, identification of patients at increased risk is still a challenge. Knowing that both neutropaenia and gastrointestinal toxicity are risk factors for bacteraemia, we aimed at comparing absolute neutrophil counts (ANC) and plasma citrulline levels (indicating enterocyte loss) in children with ALL with and without bacteraemia during induction treatment. PROCEDURE: We prospectively included 61 children with ALL treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 protocol. ANC and plasma C-reactive protein (CRP) were measured on treatment days 1, 8, 15, 22 and 29. Plasma citrulline was measured on days 1, 8, 15 and 29. Bacteraemia episodes during induction treatment were recorded retrospectively. RESULTS: Nineteen of sixty-one (31%) patients experienced bacteraemia occurring on median day 13 (range 5-20). Patients with bacteraemia during induction treatment had lower citrulline level on day 15 (P < .01) compared to patients without bacteraemia, indicating more severe enterocyte loss. Nevertheless, ANC was similar in the two patient groups on days 8 and 15. CRP was negatively correlated with same-day citrulline (P < .03 for all) and ANC (P < .04 for all). CONCLUSIONS: During chemotherapy-induced neutropaenia, plasma citrulline may help identify patients at increased risk of bacteraemia.

Additional Candida albicans administration enhances the severity of dextran sulfate solution induced colitis mouse model through leaky gut-enhanced systemic inflammation and gut-dysbiosis but attenuated by Lactobacillus rhamnosus L34.

CANDIDA ALBICANS: is abundant in the human gut mycobiota but this species does not colonize the mouse gastrointestinal tract. C. albicans administration in dextran-sulfate solution (DSS) induced-colitis mouse model (DSS+Candida) might resemble more to human condition, therefore, a DSS colitis model with Candida administration was studied; first, to test the influence of fungi in DSS model and second, to test the efficacy of Lactobacillus rhamnosus L34. We demonstrated serum (1→3)-ß-D-glucan (BG) elevation in patients with IBD and endoscopic moderate colitis in clinical remission, supporting the possible influence of gut fungi toward IBD in human. Then, in mouse model, Candida gavage was found to worsen the DSS model indicated by higher mortality rate, more severe colon histology and enhanced gut-leakage (FITC-dextran assay, endotoxemia, serum BG and blood bacterial burdens) but did not affect weight loss and diarrhea. DSS+Candida induced higher pro-inflammatory cytokines both in blood and in intestinal tissue. Worsened systemic pro-inflammatory cytokine responses in DSS+Candida compared with DSS alone was possibly due to the more severe translocation of LPS, BG and bacteria (not fungemia) from gut into systemic circulation. Interestingly, bacteremia from Pseudomonas aeruginosa was more frequently isolated from DSS+Candida than DSS alone. In parallel, P. aeruginosa was also isolated from fecal culture in most of the mice in DSS+Candida group supported by prominent Gammaproteobacteria in fecal microbioata analysis. However, L. rhamnosus L34 attenuated both DSS+Candida and DSS model through the attenuation of gut local inflammation (cytokines and histology), gut-leakage severity, fecal dysbiosis (culture method and microbiome analysis) and systemic inflammation (serum cytokines). In conclusion, gut Candida in DSS model induced fecal bacterial dysbiosis and enhanced leaky-gut induced bacteremia. Probiotic treatment strategy aiming to reduce gut-fungi and fecal dysbiosis could attenuate disease severity. Investigation on gut fungi in patients with IBD is highly interesting.

Bacteremia in Systemic Lupus Erythematosus in Patients from a Spanish Registry: Risk Factors, Clinical and Microbiological Characteristics, and Outcomes.

OBJECTIVE: To describe the incidence of bacteremia in a large multicentric cohort of patients with systemic lupus erythematosus (SLE) and their clinical characteristics and to identify risk factors. METHODS: All bacteremic episodes from the Spanish RELESSER registry were included. Clinical and laboratory characteristics concerning bacteremia and SLE status, as well as comorbidities at the time of infection, were retrospectively collected. A comparison with sex- and age-matched SLE controls without bacteremia was made. A logistic regression was conducted. RESULTS: The study included 114 episodes of bacteremia in 83 patients. The incidence rate was 2.7/1000 patient-years. At the time of bacteremia, the median age was 40.5 (range: 8-90) years, and 88.6% of patients were female. The Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index was 4 [interquartile range (IQR) 8]; 41% had an SLE flare (66% severe); Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was 3 (IQR 4). A comorbidity was recorded in 64% of cases. At the time of bacteremia, 88.6% received corticosteroids (68.6% > 10 mg/day) and 57% immunosuppressors. Gram-negative bacilli, most frequently Escherichia coli (29.8%), caused 52.6% of the episodes. The bacteremia-related mortality was 14% and bacteremia was recurrent in 27.2% of cases. A dose-response relationship was found between corticosteroids and bacteremia risk. In the multivariate analysis, these factors were associated with bacteremia: elevated creatinine (OR 1.31, 95% CI 1.01-1.70; p = 0.045), diabetes (OR 6.01, 95% CI 2.26-15.95; p < 0.001), cancer (OR 5.32, 95% CI 2.23-12.70; p < 0.001), immunosuppressors (OR 6.35, 95% CI 3.42-11.77; p < 0.001), and damage (OR 1.65, 95% CI 1.31-2.09; p < 0.001). CONCLUSION: Bacteremia occurred mostly in patients with active SLE and was frequently associated with severe flares and corticosteroid use. Recurrence and mortality were high. Immunosuppressors, comorbidities, and disease-related damage were associated with bacteremia.

Breakthrough pneumonia, meningitis and bloodstream infection due to Streptococcus pneumoniae during cefixime therapy.

Streptococcus pneumoniae is the main pathogen in invasive, life-threatening diseases such as bacteremia, meningitis, and pneumonia. We describe three cases of breakthrough pneumococcal severe life-threatening infections, including two meningitis and one bloodstream infection in patients treated with cefixime for otitis, sinusitis and pneumonia, respectively. Cefixime does not seem to be fully effective in treating invasive pneumococcal diseases. Because penicillin non-susceptibility might be linked to cefixime failure, the prompt knowledge of susceptibility to penicillin in S. pneumoniae might be very useful. Furthermore, MIC of cefixime should be measured because values >0.5 mg/L might be related to failure.

Efficacy, Toxicity, and Infectious Complications in Ruxolitinib-Treated Patients with Corticosteroid-Refractory Graft-versus-Host Disease after Hematopoietic Cell Transplantation.

Corticosteroid-refractory graft-versus-host disease (SR-GVHD) remains a significant source of morbidity after allogeneic hematopoietic cell transplantation. No standard therapy exists in this setting; however, recent studies have demonstrated a very promising role for ruxolitinib, an oral Janus kinase 1/2 inhibitor. With increasing evidence of efficacy for SR-GVHD, limited data exist describing complications of ruxolitinib use, specifically infectious complications during use in SR-GVHD. In this study we report outcomes and infectious complications at our institution with ruxolitinib use. Overall, 43 patients were treated with ruxolitinib for SR-GVHD, 19 for acute SR-GVHD and 24 for chronic SR-GVHD. With respect to acute SR-GVHD, 15 patients had grade III acute GVHD and 4 patients had grade IV acute GVHD. At 28 days, a response rate of 84% was detected. With respect to chronic SR-GVHD, 16 patients had moderate refractory disease and 8 had severe refractory disease. At around 28 days, a 63% response rate was detected. Overall, 42% of patients (n = 18) treated with ruxolitinib had a documented infectious event. Infectious events were significantly more common among patients treated for acute SR-GVHD (P < .005). Among patients treated for acute SR-GVHD, both viral (n = 11) and bacterial (n = 10) events were frequently encountered. Cytomegalovirus reactivation was detected in 4 patients without organ involvement in any patient. Bacteremia was the most common bacterial event (n = 8), and 2 patients died after development of bacteremia. Only 5 of 24 patients treated with ruxolitinib for chronic SR-GVHD developed infectious complications after initiation of therapy. Nearly an even number of viral (n = 3) and bacterial (n = 4) were detected. This study supports the use of ruxolitinib in SR-GVHD, with impressive responses observed in both acute and chronic SR-GVHD. Infectious complications were particularly frequent among patients treated for acute SR-GVHD, and nearly all these patients were concurrently on high-dose steroids while on ruxolitinib. This study suggests careful monitoring for viral reactivation is required for patients initiated on ruxolitinib, supports the role of continuing prophylactic antimicrobial measures in ruxolitinib-treated GVHD patients, and raises the question of whether bacterial prophylaxis should be considered among patients initiated on ruxolitinib for acute SR-GVHD, particularly while on high-dose steroids.

Efficacy of levofloxacin as an antibacterial prophylaxis for acute leukemia patients receiving intensive chemotherapy: a systematic review and meta-analysis.

OBJECTIVES: The incidence of febrile neutropenia (FN) in acute leukemia patients following induction or consolidation chemotherapy is high. Several clinical practice guidelines recommend the use of a fluoroquinolone prophylaxis to prevent bacterial infection in patients being prone to prolonged profound neutropenia. METHODS: This systematic review and meta-analysis aimed to investigate the efficacy and complications of levofloxacin as a prophylaxis for FN patients following chemotherapy for acute leukemia. Two databases from MEDLINE and EMBASE were searched for published studies indexed before 10 July 2018. RESULTS: A total of 862 acute leukemia patients were included, with 356 in the levofloxacin prophylaxis arm and 506 in the no-prophylaxis arm. Patients receiving levofloxacin had a significantly lower FN rate than patients who did not receive the antibiotic prophylaxis (odds ratio [OR]: 0.43, 95% confidence interval [CI]: 0.32-0.58, p < .00001, I2 = 0%). The rate of microbiologically documented infection in the no-prophylaxis group was higher than that for the levofloxacin prophylaxis group (OR: 0.45, 95% CI: 0.34-0.60, p < .00001, I2 = 0%). The bacteremia rate in the levofloxacin prophylaxis group was significantly lower than that for the no-prophylaxis group (OR: 0.45, 95% CI: 0.31-0.66, p < .00001, I2 = 0%). However, the mortality rates of the two groups were quite similar between the two groups (OR: 0.67, 95% CI: 0.34-1.33, p = .26, I2 = 0%). CONCLUSIONS: Although the levofloxacin prophylaxis for the acute leukemia patients receiving intensive chemotherapy showed advantages for infectious complications, it did not affect mortality.

Outcomes of observation without empiric intravenous antibiotics in febrile, nonneutropenic pediatric oncology patients.

There are no consensus guidelines for management of pediatric oncology patients presenting with fever and nonneutropenia, with limited research into the outcomes of withholding empiric i.v. antibiotics. We conducted a prospective cohort study assessing the safety and efficacy of observing well-appearing patients presenting with fever and nonneutropenia (absolute neutrophil count ≥ 500 cells/mm3 ). Of 238 episodes, 82.7% patients were observed with no infectious complications and low overall incidence of bacteremia (3.4%). There were no significant differences in individual clinical variables. We propose that observation alone in some well-appearing febrile pediatric oncology patients is safe and limits the use of unnecessary empiric antibiotics.