Days Of Broad-spectrum Antibiotics Research Articles

The predictive value of the MASCC score in patients with febrile neutropenia.

e23059 Background: Febrile neutropenia (FN) is a life-threatening complication in patients receiving cytotoxic chemotherapy. Guidelines classify FN as a one-time oral temperature of greater than 38.3°C or sustained temperature greater than 38°C for ≥ 1 hour with an absolute neutrophil count (ANC) of less than 500 cells/μL or an ANC expected to decrease to less than 500 cells/μL within a 48-hour period. This condition has a high rate of hospitalization and mortality. Currently, the Multinational Association of Supportive Care in Cancer (MASCC) risk score is used to classify patients as high or low risk. The current study outlines the predictive role of MASCC scoring in risk stratifying patients with FN at our institution. Methods: This is a single-center, retrospective observational study. IRB approval was obtained for this study. Electronic medical record data was reviewed to record mortality, length of stay (LOS), and antimicrobial use as primary outcomes with age at time of admission, sex, race, type of malignancy, any confirmed infection diagnosis, MASCC risk score, and subspecialist consultation as predictors of outcomes. Results: 220 records of possible FN episodes were screened, 160 were excluded leaving a total of 60 patients for review. The median age was 72.5 with 28 males and 32 females. Overall mortality rate was 10%.33 patients (55%) did not have an identifiable source of infection. Among the 27 patients with confirmed infection, 7 were associated with COVID-19, 12 had gram negative rod (GNR) sepsis and 8 were other bacterial infections. Patients with GNR sepsis had the highest mortality risk in which 4 of the 12 (33%) died. LOS was also significantly longer in patients with GNR sepsis. Lower MASCC scores were associated with identification of GNR sepsis. Of the patients with MASCC score of < 24, significantly more patients 7/20 (35%) developed GNR sepsis compared to 5/40 (12.5%) of those with MASCC score of 24 or greater (p = .004). Patients with GNR sepsis received a mean 5.7 days of broad spectrum antibiotics compared to 3 days in those without, (p < 0.001). Those with no identified infection had significantly lower LOS (4.5 days) compared to the groups with GNR sepsis (11.1 days) or other bacterial infections (10.1 days). Conclusions: Febrile neutropenia is a complication of cytotoxic chemotherapy that warrants special attention due to high mortality rates. We found lower MASCC scores were associated with GNR sepsis and that in the setting of FN these patients had higher mortality rates and longer LOS. This highlights the importance of risk stratification with MASCC index scoring as early recognition and treatment of high risk patients could lead to improved patient outcomes.

Extended antibiotic therapy is associated with a lower rate of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy in intermediate- and high-risk patients: A single-institution analysis

BackgroundClinically relevant postoperative pancreatic fistula remains a common complication after pancreatoduodenectomy. The fistula risk score is a validated tool to predict the risk of clinically relevant postoperative pancreatic fistula. To mitigate complications, we have implemented an extended antibiotic pathway for patients at increased risk of clinically relevant postoperative pancreatic fistula (fistula risk score ≥3). We report outcomes after pancreatoduodenectomy in patients at increased risk for clinically relevant postoperative pancreatic fistula who received extended antibiotic therapy compared to those who received standard perioperative antibiotics (single dose before incision). MethodsSingle-institution analysis of 87 patients who underwent elective pancreatoduodenectomy (2018–2022) with soft gland texture and fistula risk score ≥3 and were treated with (n = 34) or without (n = 53) 10 days of broad-spectrum antibiotics (piperacillin/tazobactam converted to amoxicillin/clavulanic acid at discharge) after surgery. Associations between extended antibiotics and postoperative outcomes were analyzed. ResultsBaseline clinicodemographic factors were similar between cohorts. Patients who received extended antibiotics had shorter index days (6 vs 8 days, P = .004) and 90-day composite length of stay (8.5 vs 12 days, P = .018). Patients who received extended antibiotics had lower rates of clinically relevant postoperative pancreatic fistula (11.8% vs 37.7%; odds ratio = 0.17, 95% confidence interval: 0.04–0.68), wound infections (8.8% vs 30.2%; odds ratio = 0.08, 95% confidence interval: 0.01–0.50), organ space infections (14.7% vs 43.4%; odds ratio = 0.15, 95% confidence interval: 0.04–0.52), and image-guided drain placement (8.8% vs 34.0%; odds ratio = 0.15, 95% confidence interval: 0.04–0.62). There were no Clostridium difficile infections in the extended antibiotic group. ConclusionExtended antibiotic therapy is associated with a lower rate of clinically relevant postoperative pancreatic fistula and associated complications after pancreatoduodenectomy in patients with a fistula risk score ≥3. These results form the basis of a randomized controlled trial (NCT05753735).

Refining a Protocol for Faecal Microbiota Engraftment in Animal Models After Successful Antibiotic-Induced Gut Decontamination.

BackgroundThere is mounting evidence for the therapeutic use of faecal microbiota transplant (FMT) in numerous chronic inflammatory diseases. Germ free mice are not always accessible for FMT research and hence alternative approaches using antibiotic depletion prior to FMT in animal studies are often used. Hence, there is a need for standardising gut microbiota depletion and FMT methodologies in animal studies. The aim of this study was to refine gut decontamination protocols prior to FMT engraftment and determine efficiency and stability of FMT engraftment over time.MethodsMale C57BL/6J mice received an antibiotic cocktail consisting of ampicillin, vancomycin, neomycin, and metronidazole in drinking water for 21 days ad libitum. After antibiotic treatment, animals received either FMT or saline by weekly oral gavage for 3 weeks (FMT group or Sham group, respectively), and followed up for a further 5 weeks. At multiple timepoints throughout the model, stool samples were collected and subjected to bacterial culture, qPCR of bacterial DNA, and fluorescent in-situ hybridisation (FISH) to determine bacterial presence and load. Additionally, 16S rRNA sequencing of stool was used to confirm gut decontamination and subsequent FMT engraftment.ResultsAntibiotic treatment for 7 days was most effective in gut decontamination, as evidenced by absence of bacteria observed in culture, and reduced bacterial concentration, as determined by FISH as well as qPCR. Continued antibiotic administration had no further efficacy on gut decontamination from days 7 to 21. Following gut decontamination, 3 weekly doses of FMT was sufficient for the successful engraftment of donor microbiota in animals. The recolonised animal gut microbiota was similar in composition to the donor sample, and significantly different from the Sham controls as assessed by 16S rRNA sequencing. Importantly, this similarity in composition to the donor sample persisted for 5 weeks following the final FMT dose.ConclusionsOur results showed that 7 days of broad-spectrum antibiotics in drinking water followed by 3 weekly doses of FMT provides a simple, reliable, and cost-effective methodology for FMT in animal research.

1133. Opportunities for Antibiotic Discontinuation and De-escalation after Discharge from the Emergency Department in Pediatric Patients with UTI

BackgroundIn children, urinary tract infection (UTI) represents one of the most common indications for antibiotics. While previous data has demonstrated high rates of misdiagnosis and inconsistencies with empiric antibiotics, the impact and opportunities for antibiotic reduction once final culture and susceptibility data are available, particularly in pediatric patients seen in the emergency department (ED), is unknown.MethodsThis was a retrospective study conducted over a period of 18-months, which included subjects less than 18 years of age who were discharged from the ED with a diagnosis of UTI. Episodes in which urine cultures were negative or grew only mixed urogenital flora were considered possible for discontinuation. De-escalation was considered possible in episodes in which identified bacteria were susceptible to more narrow spectrum agents than the prescribed empiric antibiotic. Rates of discontinuation and de-escalation were calculated as proportions, and excess days of therapy were described. Subjects whose empiric antibiotics were active against isolated bacteria were compared to those with bacteria resistant to empiric therapy.ResultsA total of 87 episodes of UTI were identified. Pathogenic bacteria were isolated in 51 (59%) of the 78 episodes in which urine cultures were sent, most commonly Escherichia coli (84%). Empiric antibiotic therapy and duration varied and were active against isolated bacteria in 39 (76%) of the episodes. Subjects whose antibiotics were inactive were more likely to be Hispanic and receive cephalexin [Table 3]. Antibiotics were discontinued in 3 of the 27 possible episodes (11%), resulting in 127 extra antibiotic days, median of 6 (IQR=10 days) days per episode. In 20 episodes there was an opportunity for de-escalation, but it was never attempted, leading to 131 extra days of broad-spectrum antibiotics (median 7.5 days, IQR=3).Table 1. Microbiology and resistance profile of bacteria isolated from urine cultures Table 2. Empiric antibiotic regimens, including type of antibiotic and duration Table 3. Comparison of episodes in which empiric antibiotics were active against isolated bacteria versus those in which empiric antibiotics were inactive ConclusionAntibiotics are rarely adjusted after discharge from the ED. Lack of adjustment results in unnecessary total and broad-spectrum antibiotic exposures. Initiatives designed to improve antibiotic use post-discharge could result in significant decreases in unnecessary antibiotics, and ultimately reduced rates of antibiotic resistance.Disclosures All Authors: No reported disclosures

2032. First National Survey of Antimicrobial and Antifungal Stewardship in Japan

BackgroundTo manage antimicrobial resistance, both antimicrobial stewardship (AMS) and antifungal stewardship (AFS) are needed. However, limited data show AMS and AFS practices among hospitals in Japan.MethodsWe conducted a cross-sectional nationwide study using a questionnaire distributed to hospitals that participated in a hospital epidemiology workshop in Japan in July 2018. The questions addressed activities of preauthorization, notification, and intervention within 7 or 28 days about broad-spectrum antibiotics (third- and fourth-generation cephalosporins and piperacillin–tazobactam, carbapenem, intravenous quinolone) and antifungals. Interventions to use broad-spectrum antibiotics and antifungals were compared between large (≥501 beds) and small/medium-sized (≤500 beds) hospitals.ResultsOf 240 hospitals, 39 (16%; 18 large and 21 small/medium-sized) responded. Preauthorization of using broad-spectrum antibiotics and antifungals was found in 4 (10%) and 1 (3%) hospital(s), respectively. Notification of broad-spectrum antibiotics and antifungals was found in 37 (95%) and 2 (5%) hospitals, respectively. The numbers of hospitals that intervened in the use of broad-spectrum antibiotics within 7 and 28 days were 17 (44%) and 34 (87%), respectively; those of antifungals were 3 (8%) and 10 (26%), respectively (Table 1). Interventions to use broad-spectrum antibiotics within 7 days were statistically more frequent in small-/medium-sized hospitals than in large hospitals [13 (61.9%) vs. 4 (22.2%),odds ratio = 5.7, 95% confidence interval = 1.4–23.3, p = 0.023]. All hospitals had less-frequent interventions to use antifungals within 7 days than those for antibiotics[3 (14.3%) vs. 0 (0%)] (Table 2).ConclusionSmall-/middle-sized hospitals had more frequent interventions within 7 days of broad-spectrum antibiotics than those of large hospitals, possibly because small-/medium-sized hospitals are agile and have few barriers against interventions to use broad-spectrum antibiotics. Compared with broad-spectrum antibiotics, interventions of antifungals were less frequently conducted in all hospitals. We need to emphasize the importance of AFS in Japan. Further studies on related factors are needed. Disclosures All authors: No reported disclosures.

2666. De-escalation of Broad-Spectrum Antibiotics in Hematopoietic Stem Cell Transplant Patients During Initial Episode of Febrile Neutropenia

BackgroundFebrile neutropenia (FN) is a common and serious complication in patients undergoing hematopoietic stem cell transplant (HSCT). Typically, broad-spectrum antibiotics (BSA) are promptly initiated with controversy on timing of de-escalation. ECIL 2013 guidelines suggest de-escalation after 72 hours if the patient is infection free and afebrile for at least 48 hours. Conversely, the 2011 IDSA recommends continuing BSA in patients who defervesce until absolute neutrophil count (ANC) recovery. In 2014, our center’s practice changed to early de-escalation and we sought to compare outcomes between the two practices.MethodsWe retrospectively analyzed patients who underwent a HSCT in 2013 and 2017 with an episode of FN and negative infectious work up. The standard care group (SCG) were continued on BSA until ANC recovery. The early de-escalation group (EDG) de-escalated to fluoroquinolone prophylaxis at least 24 hours prior to ANC recovery after the patient was fever free for 48 hours. The primary end-point was duration of BSA. Secondary endpoints included 30-day mortality, re-hospitalization and length of stay (LOS) from FN. Median values were compared with the Mann–Whitney test.ResultsAmong 229 HSCT patients, 155 (68%) developed FN post-transplant and of those 97 (63%) were without infection (13 EDG and 84 SCG). Initial FN duration of BSA was less in the EDG (3.09 days vs. 4.69 days, P = 0.069). Total antibiotic free days to 30 day follow-up were similar (EDG 24.08 vs SCG 25.19, P = 0.81). Duration of neutropenia was less in the SCG with 7.99 days compared with 11.69 days in the EDG (P = 0.007), but duration of initial fever was less in the EDG (2.55 days vs. 3.33 days, P = 0.023). 30 day mortality was 0% in both groups. Rates of re-hospitalization within 30 days were approximately the same (7.1% vs. 7.6%). LOS from FN was not significantly different with 6.68 days in SCG and 7.75 days in EDG (P = 0.140). More new bacterial infections were identified within 30 days of FN in the SCG than the EDG (10.7% vs. 7.6%).ConclusionEarly BSA de-escalation resulted in no significant difference in LOS from FN and fewer days of BSA with 30-day mortality and re-hospitalization rates similar. This data suggest de-escalating BSA prior to ANC recovery is likely safe and leads to less BSA exposure, but more multi-center data are needed.Disclosures All authors: No reported disclosures.

ACUTE FIBRINOUS AND ORGANIZING PNEUMONIA: A RARE CAUSE OF INTERSTITIAL LUNG DISEASE

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a rare cause of interstitial lung disease that is commonly misdiagnosed in patients presenting with diffuse alveolar opacities. Here we present a case of a 60-year-old previously healthy man who presented with fevers, shortness of breath and cough and was eventually diagnosed with steroid-responsive AFOP. CASE PRESENTATION: A 60-year-old otherwise healthy man presented to the hospital with shortness of breath, dry cough and recurrent fevers as high as 40C of two weeks duration. Physical exam was significant for a respiratory rate of 22, oxygen saturation on room air of 94% and bibasilar crackles. Lab work-up revealed elevated white blood cell count at 12K, erythrocyte sedimentation rate and C-reactive protein were highly elevated at >120mm and 190 mg/L, respectively. Respiratory viral panel and atypical respiratory bacterial culture were negative. Chest x-ray showed left basilar and right lower lobe opacities. After 4 days of broad-spectrum antibiotics, the patient failed to improve with paroxysmal high fevers and hypoxemia, requiring 3-5L of oxygen with nasal cannula. A high-resolution CT of the chest (Figure 1) showed worsening multi-focal parenchymal consolidation in the lower lobes and new patchy involvement in the upper lobes. Antibiotics were discontinued after bronchoscopy & bronchoalveolar lavage showed the absence of infectious organisms. Work-up for collagen vascular disease was negative. Biopsy of the lung parenchyma was done and showed prominent intra-alveolar fibrin, scattered inflammatory cells, and patchy intraluminal connective tissue consistent with AFOP. The patient was started on high dose oral prednisone of 80mg daily with a plan for a prolonged taper over 8 weeks. Over the next few days, his symptoms, oxygen requirements and chest X-ray findings all improved. The patient was discharged home with no oxygen supplementation. DISCUSSION: One of the rare histologic interstitial pneumonias, AFOP was first reported in 2002 (1). It is defined as a subgroup of idiopathic interstitial lung disease with acute lung injury characterized by intra-alveolar fibrin deposition and organization of loose connective tissue (2). Patients with AFOP tend to present with pulmonary as well as extra-pulmonary symptoms. Cough, both productive and non-productive, has been found to be the most common symptom, followed by dyspnea and fever. While AFOP can present as an idiopathic disease process, it has been found to be associated with other disease processes as well including autoimmune, infectious and connective tissue diseases.Treatment consists of systemic glucocorticoids and immunosuppression (3). CONCLUSIONS: AFOP is a rare histopathological diagnosis that requires a high degree of clinical suspicion for diagnosis. Increasing awareness of this entity might lead to earlier diagnosis and more prompt initiation of appropriate therapy. Reference #1: Beasley MB, Franks TJ, Galvin JR, et al. Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage. Arch Pathol Lab Med 2002;126:1064. Reference #2: Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013;188(6):733–48. Reference #3: Bhatti S, Hakeem A, Torrealba J, et al. Severe acute fibrinous and organizing pneumonia (AFOP) causing ventilatory failure: successful treatment with mycophenolate mofetil and corticosteroids. Respir Med 2009;103:1764. DISCLOSURES: No relevant relationships by Shameek Gayen, source=Web Response No relevant relationships by Xiang Liu, source=Web Response No relevant relationships by Mahmoud Madi, source=Web Response

2671 Sparing the Knife: A Case of Emphysematous Gastritis Managed Conservatively

INTRODUCTION: Emphysematous gastritis (EG) is a rare and obscure disease that carries a high mortality rate, whilst posing a diagnostic challenge. EG is caused by gas forming bacteria invading the gastric wall through disruptions in the mucosal barrier. Diagnosis is made with abdominal computed tomography (CT) scan demonstrating gas in the gastric wall. Traditionally EG has been managed surgically with partial gastrectomy, however recent case based studies support the role of conservative medical management in treating this aggressive disease. Here we present a case of non-surgically managed emphysematous gastritis. CASE DESCRIPTION/METHODS: A 28-year-old male with a history of uncontrolled type 1 diabetes mellitus (Hemoglobin A1c: 14.70) presented with a three-day history of diarrhea, melena, and orthostatic dizziness. Earlier that week the patient had been diagnosed with diabetic and initiated on metoclopramide. Despite stopping metoclopramide, the patient's diarrhea continued. Upper and lower endoscopy was performed and was largely unremarkable. The patient was discharged on erythromycin. The patient returned to the ED the following morning after developing severe abdominal pain. The physical examination revealed a soft abdomen with diffuse tenderness to palpation. Abdominal CT scan demonstrated emphysematous gastritis. Treatment was initiated with aztreonam, clindamycin, vancomycin, levofloxacin, and caspofungin. Within twenty-four hours, the patient improved clinically and repeat abdominal CT scan demonstrated significant improvement in gastric wall emphysema. After five days of broad-spectrum antibiotics the patient had complete resolution of abdominal pain. DISCUSSION: EG is a rare condition caused by gastric wall invading bacteria. Recently there has been a drastic shift in the preferred management strategy for this deadly condition that carries a mortality rate as high as 60%. A retrospective review demonstrated that prior to the year 2000 62.5% of patients with EG underwent surgical management, after 2000 this percentage dropped to 22.2%. In deciding on appropriate regimens, it is important to have broad coverage for gram-negatives, anaerobes, and fungi. Despite the lethality of EG, our case contributes to the growing body of literature that suggests that with early diagnosis and initiation of broad spectrum antibiotics, patients can be spared operative management and have successful recovery.

13. Idiopathic inflammatory myopathy, everything it should not be: asymmetrical, normal CK, high fever

IntroductionMyositis can be infective, metabolic or immune-mediated. Idiopathic inflammatory myopathy, which is immune-mediated, tends to be subacute, with symmetrical symptoms, overlap clinical features and positive autoimmune serology. We present a case of acute onset lower limb seronegative inflammatory myopathy with a normal creatinine kinase (CK), a marked acute phase response that responded promptly to immunomodulatory therapy.Case descriptionA 68-year-old man presented with a 2-week history of lower limb pain with subjective weakness, on a background of well-controlled type 2 diabetes mellitus and hypertension. He was admitted with worsening symptoms of marked left thigh pain, night sweats, and fevers.On admission, he had swinging pyrexia (above >39 °C) while remaining haemodynamically stable. He had focal tenderness over the left anterolateral thigh, with a good range of movement, normal power and no signs of focal collection or cellulitis. There were no extra-muscular features to suggest systemic infection or overlap connective tissue disease.Bloods showed C-reactive protein (CRP) 225, normal CK 212 and negative blood cultures. X-rays knee, femur and pelvis were normal. Magnetic resonance imaging (MRI) on T2, fat-suppressed STIR sequences demonstrated increased signal/oedema both thighs throughout the anterior muscle compartment and along the fascial plane, notably most severe in the left vastus lateralis. He was treated empirically for infective myositis. Despite 14 days of broad-spectrum antibiotics, he remained febrile with persistently elevated CRP. There was no focal collection, lymphadenopathy or occult malignancy on CT abdomen and pelvis. Trans-oesophageal echocardiogram showed no evidence of infective endocarditis but revealed incidental moderate aortic stenosis.The patient described persistent now bilateral thigh pain with continued normal CK and high CRP. Full autoimmune screen (ANA, ANCA, ACE and complement studies) was negative. Despite negative nuclear and cytoplasmic HEp-2 immunofluorence, extended myositis immunoblot was negative. Muscle biopsy from the left vastus lateralis demonstrated inflammation within the perimysium and perivasculature. In view of biopsy findings and no response to anti-microbial therapy, prednisolone (0.5mg/kg) with significant clinical response (resolution of fever and pain) with concurrent normalisation in CRP. The patient remains in remission following steroid reduction with no additional immunomodulatory therapy required.DiscussionWe report a case of idiopathic inflammatory myopathy presenting with predominantly asymmetrical symptoms, normal CK, marked inflammatory response and negative myositis autoantibodies. Diagnosis was confirmed on MRI and muscle biopsy. The normal CK can be explained by the histology demonstrating inflammation in perivascular regions and around muscle fibres, rather than inflammation or necrosis in the muscle fascicles and fibres themselves. Idiopathic inflammatory myopathy including sporadic inclusion-body myositis, dermatomyositis, overlap CTD myositis and polymyositis/necrotising myopathy subsets are distinguishable based on clinical features, autoantibodies, MRI and biopsy features. The table below summarises the atypical aspects of this case. Differential diagnoses for this case include atypical infection, sarcoid myopathy and amyloid myonecrosis secondary to diabetes. Table: Features of typical idiopathic inflammatory myopathy compared with this atypical case.Idiopathic inflammatory myopathiesOur patient- typical featuresOur patient- atypical featuresSymptomsPain, fever, weakness.Pain and fever.Normal power.Clinical distributionSymmetrical, proximal muscle groups.Predominantly asymmetrical (worse on left), only in thighs.AntibodiesMyositis associated autoantibodiesSeronegativeMuscle enzymesElevated CKNormal CK.Inflammatory markersNormal to slightly elevated CRPMarkedly raised CRP and WCC.MR imaging resultsFocal muscle oedema in affected musclesDiffuse and speckled muscle oedemaKey learning pointsEarly idiopathic inflammatory myopathy can have inflammation around the muscle fascicles in the perimysium. Normal CK does not rule out a diagnosis of idiopathic inflammatory myopathy.Idiopathic inflammatory myopathies can present atypically with fevers >39 °C, significantly raised inflammatory markers, and asymmetrical symptoms and MRI findings.In the absence of overlap features, normal CK and negative serology, MRI and biopsy can delineate the type of myositis and direct management.Conflicts of interestThe authors have declared no conflicts of interest.

Frequency and Determinants of Invasive Fungal Infections in Children With Solid and Hematologic Malignancies in a Nonallogeneic Stem Cell Transplantation Setting: A Narrative Review.

Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in children with cancer. An overview of studies on the frequency and determinants of IFI in pediatric oncology patients in nonallogeneic stem cell transplantation settings is lacking. We performed a literature review in Pubmed and Embase, and included 13 prospective and 23 retrospective studies. The IFI frequency (proven/probable based on EORTC criteria) in nonallogeneic stem cell transplantation pediatric cancer patients ranged between 1.0% and 38.0%, with the highest frequencies reported in hematologic malignancies. The most common fungal species seen in the studied population was Candida, followed by Aspergillus. IFI are not well investigated in solid tumor patients. Significant recurrent determinants from univariate analysis were the diagnosis acute myeloid leukemia, (prolonged) neutropenia and an older age (above 10 years). The only 2 significant determinants based on multivariate analysis were the preceding number of days of broad-spectrum antibiotics (odds ratio, 1.05; 95% confidence interval, 1.02-1.07; P=0.0006) and the number of days of corticosteroids (odds ratio, 1.05; 95% confidence interval, 1.02-1.09; P=0.005), that were both based on a group of acute myeloid leukemia patients only. Future studies are necessary to determine the frequency and determinants of IFI in pediatric oncology including a representative number of solid tumor patients.

Diagnostic Performance of T2Candida Among ICU Patients With Risk Factors for Invasive Candidiasis.

BackgroundInvasive candidiasis (IC) comprises candidemia and deep-seated candidiasis. Blood culture (BC) is the gold standard test, but sensitivity is low. T2Candida is a new diagnostic test. We investigated the performance of T2Candida, BC, and Candida mannan antigen (MAg) for detection of IC in a high-risk intensive care unit (ICU) population.MethodsOne-hundred twenty-six ICU patients at high risk of IC with sepsis despite 3 days of broad-spectrum antibiotics were included. Paired BC, T2Candida, and MAg were obtained twice weekly (334 sets). Patients were classified into proven, likely, possible, or unlikely IC based on patient record review.ResultsAt enrollment, 92 (77%) patients were receiving antifungal therapy (mainly fluconazole 66%). Fifteen (11.9%) patients were positive by BC (n = 4), T2Candida (n = 11), or MAg (n = 10). The T2Candida species distribution at inclusion (Candida albicans/Candida tropicalis: 8/11 [72.3%] and Candida glabrata/Candida krusei: 3/11 [27.3%]) was supported by the identification of BC or colonizing isolates in 10/11 cases. Patients were classified with proven (11), likely (6), possible (11), and unlikely (98) IC. Defining IC as proven/proven&likely/proven&likely&possible, respectively, the sensitivity was as follows: T2Candida (55%/59%/39%), BC (45%/29%/ 8%), and MAg (36%/41%/32%). The negative predictive value was similar across the tests for proven vs others and proven/likely vs others (94%–96% and 90%–95%, respectively). For test combinations including T2Candida, the sensitivity increased to 64%–65%, without hampering the positive predictive value.ConclusionsIn conclusion, although the diagnostic performance was modest for all the tests, the combination of T2Candida and BC seemed to have the best diagnostic performance, and thus implementation of T2Candida may improve the diagnosis of IC.

Staphylococcus lugdunensis Endocarditis in a Patient Being Treated for Pyelonephritis

Staphylococcus lugdunensis
 Endocarditis in a Patient Being Treated for Pyelonephritis
 
 Christopher
 M Peake1, Nicholas Faure-Walker2, Elli DeMertzi2
 
 1St George’s University Hospital,
 Blackshaw Road, Tooting, London, UK
 
 2Kingston Hospital, Galsworthy Road,
 Kingston-upon-Thames, UK
 
  
 
 ABSTRACT
 
 A 35
 years old female with known chronic left pelvo-ureteric junction (PUJ)
 obstruction presented with recurrent pyrexia and left loin pain and was treated
 for pyelonephritis. She had a history of severe aortic valve (AV)
 regurgitation. After five days of broad spectrum antibiotics and a percutaneous
 nephrostomy, her fevers persisted. Staphylococcus
 lugdunensis was isolated from her blood culture and she was diagnosed with
 mitral valve endocarditis following an echocardiogram. She was transferred to a
 tertiary cardiothoracic unit where she underwent a mitral and aortic mechanical
 valve repair. After 6 weeks of intravenous antibiotic treatment she was
 discharged without signs of infection but with poor cardiac function. S. lugdunensis is a virulent organism
 which is thought to be underdiagnosed and is associated with aggressive and
 destructive endocarditis. An awareness of the organism as well as prompt
 diagnosis and treatment with effective multi-disciplinary management is needed
 to avoid substantial morbidity in these patients. 
 
 Whilst
 S. lugdunensis is known to cause
 invasive endocarditis, it has never been reported following pyelonephritis. The
 significance of this case is that despite receiving appropriate and timely
 treatment the patient was left with deteriorating cardiac function. This is an
 important reminder that this organism must be taken seriously when isolated in
 the context of infection. J Microbiol
 Infect Dis 2018; 8(1):37-40
 
 Keywords: Staphylococcus lugdunensis, endocarditis,
 pyelonephritis, heart valves, urinary tract

Emphysematous Gastritis: A Rare and Lethal Cause of Severe Abdominal Pain

Introduction: Emphysematous gastritis (EG) is an exceedingly rare cause of severe abdominal pain with an associated mortality reported at greater than 60%. We present 3 cases of EG at our hospital over the course of one year. Case 1: 68-year-old male with a history of osteoarthritis on chronic excessive doses of ibuprofen presented with a subdural hematoma due to a mechanical fall and a urinary tract infection (UTI). While hospitalized, the patient developed severe, diffuse abdominal pain, nausea, and worsening leukocytosis despite appropriate antibiotic coverage for his UTI. An abdominal CT revealed signs of EG. Case 2: 62-year-old woman who underwent a laparoscopic paraesophageal hernia repair with Nissen fundoplication and gastropexy presented postoperatively with one day of severe epigastric pain, pleuritic chest pain, and leukocytosis. Originally thought to have gastroparesis, initial therapy with metoclopramide was ineffective. Further evaluation with abdominal CT revealed signs of EG. Case 3: 84-year-old male with history of diabetes and ischemic stroke presented with multiple days of diarrhea, coffee ground emesis and severe epigastric pain. He was admitted for upper gastrointestinal bleed work up. Prior to performing EGD, he decompensated and was transitioned to the ICU on mechanical ventilation. A worsening leukocytosis prompted abdominal CT, revealing signs of EG. Results: The findings common to all presentations were worsening leukocytosis, abdominal pain, and imaging revealing air in the gastric wall and portovenous system. The first case was managed with broad spectrum antibiotics and bowel rest. Upper endoscopy (EGD) confirmed a large ulcer in the fundus and body, that resolved on follow-up EGD. The second case had an EGD showing severe gastritis, and patient improved with no further intervention or antibiotics. The third case expired after multiple days of broad spectrum antibiotics and was too unstable to undergo EGD or surgery. Discussion: EG is characterized by severe abdominal pain and leukocytosis with imaging confirming intramural gastric air and portovenous air. Risk factors associated with EG include high dose NSAIDs and gastric surgery. CT scan is imperative for early diagnosis and distinguishing from other etiologies, as EG can be rapidly lethal. EGD can be performed despite the CT findings which can reveal varying degrees of inflammation. It is unclear if empiric treatment with antibiotics may have a significant benefit.

Clinical considerations in the early treatment of invasive mould infections and disease.

Different therapeutic strategies for invasive fungal diseases have been explored, each with particular strengths and weaknesses. Broad-spectrum antifungal prophylaxis seems logical, but selective use is important due to its substantial disadvantages, including interference with diagnostic assays, selection for resistance, drug toxicity and drug-drug interactions. Antimould prophylaxis should be restricted to high-risk groups, such as patients undergoing intensive chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome, allogeneic HSCT patients with prior invasive fungal infection, graft-versus-host-disease or extended neutropenia, recipients of a solid organ transplant, or patients with a high-risk inherited immunodeficiency. An empirical approach, whereby mould-active therapy is started in neutropenic patients with fever unresponsive to broad-spectrum antibiotics, is widely applied but incurs the clinical and cost penalties associated with overtreatment. A benefit for all-cause mortality using empirical therapy has not been shown, but it is recommended for high-risk patients who remain febrile after 4-7 days of broad-spectrum antibiotics and in whom extended neutropenia is anticipated. There is growing interest in delaying antifungal treatment until an invasive fungal infection is confirmed ('pre-emptive' or 'diagnostics-driven' management), prompted by the development of more sensitive diagnostic techniques. Comparisons of empirical versus pre-emptive regimens are sparse, particularly with modern triazole agents, but treatment costs are lower with pre-emptive therapy and the available evidence has not indicated reduced efficacy. Pre-emptive treatment may be appropriate in neutropenic patients who remain febrile after administration of broad-spectrum antibiotics but who are clinically stable. Further work is required to define accurately the specific patient subgroups in which each management approach is optimal.

Evaluation of empiric antibiotic de-escalation in febrile neutropenia.

Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated guideline on the use of antimicrobial agents in neutropenic patients with cancer indicates that patients who have completed an appropriate treatment course of broad-spectrum antibiotics, with resolution of signs and symptoms of infection but persistent neutropenia, can be de-escalated to oral fluoroquinolone prophylaxis until ANC recovery. The primary objective of this retrospective investigation was to evaluate the safety and efficacy of de-escalating broad-spectrum antibiotics in patients remaining neutropenic after at least 14 days of empiric broadspectrum antibiotics for febrile neutropenia compared to patients continuing broad-spectrum antibiotics until ANC recovery. There were 16 patients (61.5%) in the comparator group who met the primary endpoint of remaining afebrile and without escalation of antibiotics for at least 72 hours after 14 days of broad-spectrum antibiotics and 21 patients (80.7%) in the de-escalation group who met the primary endpoint of remaining afebrile and without reinitiation of broad-spectrum antibiotics for at least 72 hours after de-escalation to levofloxacin therapy (p = 0.11). Mean total duration of broad-spectrum antibiotic therapy was 23.5 ± 1.5 days in the comparator group versus 22.2 ± 1.43 days in the de-escalation group (p = 0.39). Results of this investigation indicate that broad-spectrum antibiotics can be safely de-escalated to levofloxacin prophylaxis prior to ANC recovery in select patients. This practice may decrease the duration of broad-spectrum antibiotic exposure and associated complications.

Cytomegalovirus-Associated Esophagopulmonary Fistula in an AIDS Patient Successfully Treated with Esophageal Stenting

Introduction: A 46-year-old man with AIDS and poor antiretroviral adherence presented with a 12-day history of chest pain, dyspnea, cough, and fever. Examination revealed tachycardia, cachexia, and thrush. One month prior, CD4 count was 9/mm3 and HIV viral load was 57,647 copies/mL. Chest CT noted a dominant cavitary mass in the right upper lobe, several smaller pulmonary cavitations, and proximal esophageal dilatation. Treatment for bacterial pneumonia and candidiasis was started. Initial infectious studies, including acid-fast sputum smears, were negative. Despite 7 days of broad-spectrum antibiotics, his cough worsened, serial chest imaging noted disease progression, and sputum culture grew MRSA and commensal bacteria. Three weeks into his course, he developed dysphagia and odynophagia. Serum PCR for Cytomegalovirus (CMV) was 701 copies/mL. EGD noted a cratered 5-cm longitudinal ulcer in the proximal esophagus (Figure 1A) and a 1-mm fistulous opening within the ulcer (Figure 1B). Barium esophagram revealed a communication between the proximal esophagus and right hemithorax (Figure 1C). Chest CT demonstrated tracking of barium from the esophagus into the dominant pulmonary cavity (Figure 1D). These findings were consistent with the diagnosis of an esophagopulmonary fistula. On repeat EGD, biopsies of the ulcer were obtained, followed by placement of a 12-cm fully-covered metal stent across the fistula. Pathology showed esophageal squamous epithelium, inflamed reactive stroma, and acutely inflamed columnar respiratory-type mucosa with scattered CMV-positive cells, confirmed on immunohistochemistry (Figure 1E). The patient received valgancyclovir for 21 days and the stent was removed 35 days after placement with resolution of the ulcer. Repeat barium esophagram showed no structural abnormalities. We present the first reported case of a CMV-associated esophagopulmonary fistula successfully treated with antiviral therapy and a fully-covered metal esophageal stent. Esophagorespiratory fistulas are rare and usually associated with malignancy or post-operative complications. Use of fully-covered metal stents has been described in the treatment of esophageal fistulas and leaks with variable success.Figure 1

Gunshot wound contamination with squirrel tissue: wound care considerations.

While report of animal bites contaminating wounds is reported commonly, direct wound contamination with squirrel flesh has never been reported in the literature. The patient suffered an accidental self-inflicted gunshot wound that drove squirrel flesh and buck shot deep within his right buttock. This case outlines his hospital course and wound treatment. The patient was treated with ten days of broad spectrum antibiotics, extensive debridement of the wound in the operating room, and further treatment of the wound with a vacuum dressing system. While squirrel tissue and buckshot had to be removed from the wound on day six of the hospital stay, the patient remained afebrile without signs or symptoms of systemic illness.

Clostridium difficile Infection in Pediatric Acute Myeloid Leukemia

The prevalence and severity of Clostridium difficile infection (CDI) has increased over time in adult patients, but little is known about CDI in pediatric cancer. The primary objectives were to describe the incidence and characteristics of CDI in children with de novo acute myeloid leukemia (AML). The secondary objective was to describe factors associated with CDI. We performed a multicenter, retrospective cohort study of children with de novo AML and evaluated CDI. Recurrence, sepsis and infection-related death were examined. Factors associated with CDI were also evaluated. Forty-three CDI occurred in 37 of 341 (10.9%) patients during 42 of 1277 (3.3%) courses of chemotherapy. There were 6 children with multiple episodes of CDI. Three infections were associated with sepsis, and no children died of CDI. Only 2 children had an associated enterocolitis. Both days of broad-spectrum antibiotics (odds ratio 1.03, 95% confidence interval: 1.01 to 1.06; P = 0.003) and at least 1 microbiologically documented sterile site infection (odds ratio 10.81, 95% confidence interval: 5.88 to 19.89; P < 0.0001) were independently associated with CDI. CDI occurred in 11% of children receiving intensive chemotherapy for AML, and outcomes were not severe. CDI is not a prominent issue in pediatric AML in terms of prevalence, incidence or associated outcomes.

Invasive fungal infections in paediatric acute myeloid leukaemia

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in paediatric acute myeloid leukaemia (AML). This study describes risk factors for IFI and IFI-related sepsis in this population. We conducted a population-based, retrospective cohort study of children with AML in Canada. IFIs during chemotherapy and prior to haematopoietic stem cell transplantation, relapse, persistent disease or death were identified. Risk factors for proven or probable IFI were examined. Among courses complicated by IFI, risk factors for sepsis were also evaluated. There were 341 children with AML included of which 41 (12.0%) experienced 46 different episodes of IFI. Candida species accounted for 23 (50.0%) of IFIs and Aspergillus spp. accounted for 14 (30.4%). Days of broad-spectrum antibiotics, days of corticosteroids and neutropenia at start of the course were independently associated with IFI. Only days of fever were independently associated with IFI-related sepsis. Invasive fungal infections occurred in 12.0% of paediatric AML patients. Risk factors for IFI and IFI-related sepsis were identified. This knowledge may help to consider targeted strategies.

Galactomannan-guided preemptive vs. empirical antifungals in the persistently febrile neutropenic patient: a prospective randomized study

Patients with neutropenic fever after 4-7 days of broad-spectrum antibiotics are given antifungals empirically. This strategy may lead to over-treatment. Patients with hematological malignancies undergoing intensive chemotherapy or hematopoietic stem cell transplantation were randomized to two arms. Patients in the 'preemptive' arm had regular galactomannan (GM) assays, and received caspofungin, amphotericin or voriconazole (CAV) for persistent febrile neutropenia if they had two positive GM results, or a positive GM result and a computed tomography (CT) of the thorax suggestive of invasive pulmonary aspergillosis (IPA). Patients in the 'empirical' arm received CAV in accordance with established guidelines. Of 27 episodes in the preemptive arm, two cases of IPA were picked up by monitoring. In six episodes, CAV was started despite persistently negative GM readings. One additional patient received CAV for a false-positive GM. Of 25 episodes in the empirical arm, CAV was started empirically in 10, one of whom had CT features of IPA. By intent-to-treat and evaluable-episode analyses, respectively, the preemptive approach saved 11% and 14% of patients from empirical antifungals. Twelve-week survival was 85.2% in the preemptive arm and 84% in the empirical arm. A preemptive approach may reduce empirical antifungal use without compromising survival in persistently febrile neutropenic patients.