Empirical Antibacterial Treatment Research Articles

Clinical features of omicron SARS-CoV-2 variants infection associated with co-infection and ICU-acquired infection in ICU patients.

Although the decreasing rate of hospital admission in the omicron wave has led countries to loosen control, still the patients requires ICU admission. It is common for viral respiratory infections to be co-infected with bacteria. However, the difference between co-infection and ICU-acquired infection on their clinical characteristics and outcomes during the Omicron wave was little reported. Clinical and microbiological data were collected from ICU patients with omicron infection between April 1st, 2022, and May 31th, 2022 and a comprehensive comparative study of the clinical characteristics and endpoint were conducted. The Omicron SARS-CoV-2 variants-infected patients requiring intensive care had high rates of co-infection (42.55%). Additionally, the ICU COVID-19 patients with co-infection showed more severe clinical features compared to those with ICU-acquired infection. Furthermore, Multivariate Cox analysis demonstrated that co-infection (hazard ratio: 4.670, p = 0.018) was a significant risk factor for poor outcomes in ICU patients with COVID-19. Besides, Kaplan-Meier survival curve analysis revealed that COVID-19 patients with co-infection had a significantly shorter 28-Day survival time compared to those with ICU-acquired infection (p < 0.001). Finally, our investigation identified a significant association between the presence of Candida app. in the broncho-alveolar lavage and an elevated risk of mortality (OR: 13.80, p = 0.002) and invasive ventilation (OR: 5.63, p = 0.01). Co-infection is prevalent among patients requiring intensive care and is linked to unfavorable outcomes in the Omicron wave. Consequently, more attention may be needed for the empirical antibacterial treatment in ICU patients within the COVID-19 Omicron variant, especially anti-fungi.

Severe and complicated soft tissue infections: a single-centre case series.

To assess the demographic and clinical characteristics, laboratory findings, and economic burden of patients with a diagnosis of complicated skin and soft tissue infection (cSSTI). The demographic and clinical characteristics, laboratory findings, surgical interventions, cost of treatment, and outcome of patients diagnosed with cSSTIs between January 2017 and December 2019 were retrospectively analysed. A total of 24 patients with cSSTIs were included in the study. The median age was 53 (22-85) years, and 14 (58%) were female. The most common comorbidity was diabetes (54%). On admission, 75% of patients presented with sepsis, and 70% had a high-grade Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score. The causative microorganism was isolated from 21 (87%) patients, and the multidrug resistance rate of Gram-negative bacteria was 50%. The median number of debridements was 3 (1-12). In all, 11 patients were followed up in the intensive care unit, and the mortality rate was 29%. The presence of confusion (p=0.025), causative Gram-negative microorganisms (p=0.009), hyponatraemia (p=0.034), the need for intensive care (p=0.001), anti-meticillin-resistant Staphylococcus aureus antibiotics (p=0.023) and the rate of antibiotic changes during treatment (p=0.019) were significantly higher in the non-survival patient group. Hyponatraemia was a significant independent risk factor for mortality (p=0.048). The median cost of per-patient treatment was $9453 USD in the non-surviving and $1536 in the surviving group. It is important to know possible factors and local resistance rates at the beginning of empirical antibacterial and surgical treatment. The presence of hyponatraemia, sepsis and a high LRINEC score can be considered to be the mortality predictors.

Bacterial peritonitis in paediatric appendicitis; microbial epidemiology and antimicrobial management

BackgroundAppendicitis remains a common surgical emergency in children. Empirical antibacterial treatment is indicated to reduce infective complications. We investigate the bacterial pathogens identified intra-operatively during appendectomies in children to guide empirical surgical antimicrobial prophylaxis options.MethodsA retrospective analysis of patients (< 18 years old) undergoing an appendectomy across a multisite London hospital (Nov 2019–March 2022) was undertaken. Patient-related outcomes including length of hospital stay (LOS), days of antibacterial therapy (DOT), intra-operative microbiology and post-operative radiology reports were interrogated.Results304 patients underwent an appendectomy during this period; 39.1% of patients had intraoperative samples cultured. Bacterial pathogens were found in 73/119 (61.3%) cases; the most common isolates being Escherichia coli (42.0%), Pseudomonas aeruginosa (21.0%), milleri Streptococcus spp. (14.3%) and Bacteroides fragilis (5.9%). Polymicrobial infection was common (32/73). Isolation of Pseudomonas spp. from intra-operative sampling was associated with a greater LOS (7.0 vs. 5.0 days; p = 0.011) but nil effect on the incidence of postoperative collections. Presence of milleri Streptococcus spp. was associated with longer LOS (7.0 vs. 5.0 day; p = 0.007), DOT (12.0 vs. 8.5 day; p = 0.007) but had no observed outcome on postoperative collections (29.4% vs. 18.6%; p = 0.330). 48% of E. coli positive cultures were co-amoxiclav resistant and prolonged LOS compared to the non-resistant group (7.0 vs. 5.0 days; p = 0.040) but had no difference in post-operative collections (29.2% vs. 17.9%; p = 0.260).ConclusionA high proportion of children with appendicitis have Pseudomonas spp. isolated, leading to a prolonged LOS. Evolving Enterobacterales resistance and the presence of Pseudomonas spp. necessitate extended antibacterial coverage for paediatric appendectomies with evidence of peritonitis.

The Pathogen Isolates in Chronic Wound Infections in Poland.

Chronic wound infection is one of the factors that hinder or prevent its healing. The incidence of infection may vary depending on the type of wound. It is estimated that clinically significant infection in diabetic foot syndrome occurs in up to 30% of patients. Accurate diagnosis of infection features and proper microbiological tests are crucial for introducing of appropriate local and often systemic treatment. The aim of the study was a comparative analysis of the microbiota found in infected chronic wounds in patients from Poland, consulted on an outpatient basis at a wound care center in 2013-2021. The indication for microbiology culture tests was the detection of local signs of infection, and sampling was preceded by appropriate wound debridement. The standard culture technique was a deep-tissue biopsy. Material for the study was collected from 1,199 patients. Overall, 3,917 results of microbiological tests were subjected to retrospective analysis. The paper presents the results in the form of the number of cultured microorganisms and their relative incidence as percentages, considering the division into the types of wounds from which the material was obtained. The most frequently isolated microorganisms in the analyzed group were Staphylococcus aureus (14.3% of this group were MRSA - methicillin-resistant Staphylococcus aureus) and Enterococcus faecalis (2.4% of this group were VRE - vancomycin-resistant Enterococcus). Further analysis of such an extensive database, especially regarding drug susceptibility of isolated microorganisms, seems crucial to elaborate new recommendations for empirical antibacterial treatment of infected chronic wounds.

Microbiota Assessment of Pediatric Simple and Complex Acute Appendicitis.

Background and Objectives. The aim of this study is to determine the prevailing microbiota in samples from pediatric patients with acute appendicitis, as well as evaluate the antibacterial sensitivity of the isolated microorganisms, comparing the data obtained with the clinic’s antibacterial therapy guidelines. Materials and Methods. The study group consisted of 93 patients between the ages of 7 and 18. All patients underwent a laparoscopic or conventional appendectomy. The children were hospitalized with signs and symptoms suggestive of acute appendicitis. Microbiological cultures from the appendix and abdominal cavity were collected intraoperatively. Results. E. coli was identified in most cases irrespective of the clinical presentation of acute appendicitis. Most strains were susceptible to ampicillin and amoxicillin/clavulanic acid. Five strains of E. coli produced extended spectrum beta-lactamase (ESBL). Pseudomonas aeruginosa (P. aeruginosa) was the second most commonly isolated causative agent. Furthermore, it was common in cases of acute complex appendicitis. Most strains of P. aeruginosa were resistant to amoxicillin/clavulanic acid, ertapenem, ampicillin and cefotaxime, yet were susceptible to ceftazidime. Regardless of the clinical presentation, the samples yielded mixed isolates. Conclusion. E. coli is the main causative agent of acute appendicitis in the pediatric population displaying susceptibility to various antibiotics. P. aeruginosa was more prevalent in cases of acute complex appendicitis. P. aeruginosa isolates were susceptible to ceftazidime; however, they were resistant to cefotaxime, which should, therefore, be removed from guidelines for empirical antibacterial treatment of acute appendicitis due to phenotypic resistance of P. aeruginosa. We recommend antibiotics with distinct implementation to avoid antibiotic resistance.

Clinical and microbiological features of drowning-associated pneumonia: a retrospective multicentre cohort study

ObjectivePneumonia is the most frequent infectious complication in patients who have experienced drowning that requires intensive care unit (ICU) admission. We aimed to describe clinical, microbiological, and therapeutic data as well as predictors and impacts of such pneumonia on patients' outcomes. MethodsWe conducted a retrospective, multicentre study (2013–2020) of 270 consecutive patients admitted for drowning to 14 ICUs in Western France. Their baseline characteristics and outcomes were compared according to the occurrence of drowning-associated pneumonia (DAP), defined as pneumonia diagnosed within 48 hours of ICU admission. A Cox regression model was used to compare survival on day 28, and logistic regression was used to identify risk factors for DAP. Microbiological characteristics and empirical antibacterial treatment were also analysed. ResultsAmong the 270 patients admitted to the ICU for drowning, 101 (37.4%) and 33 (12.2%) experienced pneumonia and microbiologically proven DAP, respectively. The occurrence of pneumonia was associated with higher severity scores at ICU admission (median Simplified Acute Physiology Score II, 34 [interquartile range {IQR}, 25–55] vs. 45 [IQR, 28–67]; p 0.006) and longer ICU length of stay (2 days [IQR, 1–3] vs. 4 days [IQR, 2–7]; p < 0.001). The 28-day mortality rate was higher among these patients (29/101 [28.7%] vs. 26/169 [15.4%]; p 0.013). Microbiologically proven DAP remained associated with higher 28-day mortality after adjustments for cardiac arrest and water salinity (adjusted hazard ratio, 1.86 [95% CI, 1.06–3.28]; p 0.03). A microbiological analysis of respiratory samples showed a high proportion of gram-negative bacilli (23/56; 41.1%), with a high prevalence of amoxicillin-clavulanate resistance (12/33; 36.4%). ConclusionsPneumonia is a common complication in patients admitted in the ICU for drowning and is associated with increased mortality.

Cefotaxime resistance in bile samples is an independent predictor of deep infectious complications after pancreaticoduodenectomy in patients with endoprosthesis.

Bacteriobilia may increase the rate of deep infectious complications (DIC) after pancreaticoduodenectomy. To better adjust prophylactic and empirical antibacterial treatment, we aimed to characterize bacteriobilia in patients with preoperative endoprosthesis, and its association with postoperative DIC. All patients who underwent pancreaticoduodenectomy in our center between 2010 and 2019 were included. The association between microbiological findings from bile samples, and postoperative DIC was analyzed, and we compared microbiology data between 2010-2014 and 2015-2019 periods. We enrolled 578 patients (median age 67 years [59-72], 58.7% males), of whom 220 (38.1%) had preoperative biliary endoprosthesis, with 197 (89.5%) positive preoperative bile samples pathogens were Enterobacterales, enterococci, and Candida albicans. The incidence of DIC was similar in patients with or without endoprosthesis (20.4% vs 17.8%, P=.352). Bacterial isolates collected during 2015-2019 were more resistant to cefotaxime than those recovered from 2010-2014 (45.5% vs 25.5%, P=.009). The only independent risk factor for DIC in patients with endoprosthesis was cefotaxime resistance in bile (hazard ratio 3.027 [1.115-8.216], P=.03). The incidence of DIC is high after pancreaticoduodenectomy, with or without endoprosthesis, despite routine postoperative treatment. Cefotaxime resistance, the only independent predictor of DIC in patients with endoprosthesis, has increased over time. Hence, cefotaxime may no longer be an appropriate empirical treatment.

Empiric Guideline Therapy for Simple Urinary Tract Infection at Outpatient Clinics: A Prospective Observational Study

Background: Community-acquired urinary tract infection is a widespread problem encountered in the outpatient clinics of most hospitals. UTI has various clinical presentations; some are simple UTIs that can be managed with outpatient antibiotics. The current treatment of UTI is empirical, based on the limited and predictable spectrum of etiological microorganisms. Objectives: To collect information on the susceptibility tests of microorganisms in simple urinary tract infections (UTIs) and outline the best empiric antimicrobial prescribed for them. Methods: A total of 117 patients from 14 to 70 years of age (mean age = 43.61years, standard deviation = + 24.5) received the care of our surgical and urological outpatient clinics in Alnuman Teaching Hospital, Baghdad, Iraq, between March 1, 2019, and September 1, 2020. The patients who were showing symptoms of simple uncomplicated UTI and were prescribed empiric antibacterial treatment and requested for a sample of midstream urine for culture and sensitivity tests were enrolled in this prospective study. The susceptibility test for (ciprofloxacin, trimethoprim, gentamycin, and ceftriaxone) was performed using the Kirby–Bauer disc diffusion method. The data were input into SPSS 22.0 for statistical analysis. Pearson’s chi-squared test was used to compare parameters. The data have been presented as the number of variables (n) and percentages (%). Statistical significance was set at P &lt; 0.05. Results: The frequencies of isolated uropathogens were as follows: E. coli, n = 65 (77.4%); Klebsiella spp., n = 9 (10.7%), Proteus spp., n = 3 (3.57%), Enterobacter spp., n = 3 (3.57%)., Staphylococcus spp., n = 2 (2.38%)., Pseudomonas spp., n = 1 (1.19%), and Candida spp., n = 1 (1.19%). The resistance rates of the most prevalent microorganisms were E. coli isolates to trimethoprim, ciprofloxacin, gentamycin, and ceftriaxone. The lower resistance rates to ceftriaxone in E. coli isolates (29.7%) was not clinically significant, with p &lt; 0.05. Gentamycin showed significant sensitivity and resistance rates of 58.3% and 33.3% respectively, among the antimicrobials used (p &lt; 0.05). The clinical effectiveness of empirical antimicrobial use in the treatment of simple UTIs showed no statistically significant correlation with P &lt; 0.05. Conclusions: Trimethoprim and ciprofloxacin should not be used in empirical therapy for UTIs because of their increased resistance rates. A review of the local guidelines should be considered.

Mixed Sexually Transmitted Infections in Infertile Couples: Empirical Treatment and Influence on Semen Quality

Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) and Ureaplasma urealyticum (UU) are common sexually transmitted infections (STIs) that are diagnosed in infertile couples (cps). In cases with their simultaneous presence in a patient (mixed STI, MSTIs), treatment is complicated by the different sensitivity of microorganisms to antibacterial drugs. Moreover, in cases of complicated infections, the empirical treatment should be started before obtaining the results of drug susceptibilities. The objective of the current study is to find the effective and well-tolerated combination of drugs for the empirical antibacterial treatment of mixed STIs presented by TV, MG and UU in infertile couples. We also aimed to establish the influence of mixed STIs on semen quality. Our prospective study included 154 infertile couples (308 patients) with confirmed symptomatic MSTIs in one of the couples caused by the simultaneous presence of TV, MG and UU. All couples were randomized on three groups for empirical treatment: Group 1 (n=49 cps, 98 pts) who were treated by initial prescribing of anti-trichomoniasis drug Secnidazole, 2.0 g po followed by Azythromycin 500 mg on day 1 continuing by 250 mg on days 2-7; Group 2 (n=52 cps, 104 pts: Secnidazole, 2.0 g po followed by Josamycin 1000 mg bid for 12 days); Group 3 (n=53 cps, 106 pts: Secnidazole, 2.0 g po followed by Moxifloxacin 400 mg once daily for 12 days). The endpoints were clinical and microbiological cure rates as well as the frequency of side-effects in analyzed groups. We determined the basic parameters of the spermogram and Deoxyribonucleic acid (DNA) fragmentation levels in 59 patients with MSTIs before and at the 3rd, 6th and 9th month after pathogens eradication comparing them with results in 63 healthy sperm donors. After the treatment, clinical cure rates in analyzed groups were 82.6% (Group 1) vs. 96.1% (Group 2) vs. 92.3% (Group 3). Microbiological cure rates (UU+MG) were 73.9% vs. 97.1% vs. 84.5% correspondingly (p<0.05). TV microbiological cure rates were 97.8% vs. 98.0% vs. 96.1% (p>0.05). Side-effects were registered in 28.6% vs. 12.5% vs. 18.9% cases correspondingly (p<0.05). In MSTIs patients, we registered the increasing DNA fragmentation rates, leucocytes count and decreasing semen volume, motility, vitality, sperm concentration, total spermatozoa number and number of spermatozoa with normal morphology. At the 6th month after complete pathogens eradication, these parameters approached normal values. At the present time, the combination of Secnidazole+Josamycin can be considered the most effective and well-tolerated for the empirical treatment in patients with MSTIs presented by TV, MG and UU. Complete eradication of these MSTIs in males improves their semen parameters.

Overview of the epidemiology, etiology, clinic, diagnostics and treatment of urosepsis

Rūta Marija Rainytė1, Agnė Šaltkauskaitė2, Bernadeta Kalvelytė1 1Lithuanian University of Health Sciences, Medical Academy, Faculty of medicine 2Department of Family medicine, Lithuanian University of Health Sciences Abstract Urosepsis is a term which describes a type of sepsis caused by infection in the urinary tract. This type of sepsis is one of the most common. The main reason of urosepsis is urinary tract obstruction. If urosepsis is suspected, patient’s condition should be assessed using qSOFA score and in case there are indications – blood culture and culture from suspected infection area (urine) should be taken. Survival rate depends on how fast the treatment by antibiotics begins. If a septic patient doesn’t get help fast, this state could lead to multiple organ dysfunction following respiratory failure, renal failure, hepatic impairment and disseminated intravascular coagulation. That is the reason why empirical antibacterial treatment should be given as soon, as the diagnosis of urosepsis is made. Also, it is important to monitor and correct vital signs such as blood pressure, heart and respiratory rate and saturation if it is needed. The aim of this publication is to review epidemiology, etiology, clinical manifestation, diagnostics and treatment options of urosepsis from scientific literature. Aim: to analyze factors which indicate and are used in urosepsis diagnostics and overview recommendations of urosepsis treatment. Methods: a systematic search of the literature was made using PubMed database. The keywords for this analysis were: urosepsis, etiology, symptoms, diagnostics, treatment, qSOFA. Over 90 articles were read of which 16 were selected for this review. Results. After the literature analysis was made, it came to conclusion that in urosepsis diagnostics there are not any specific biomarker which could help to detect sepsis. Urosepsis diagnosis should be formed using clinical evaluatian, laboratory results and visual imaging methods. The most important symptoms for urosepsis are increasd respiratory rate (more than 22 breaths per minute), impaired consciousness which is lower than 15 using Glasgow coma scale and decreased sistolic blood pressure (lower than 100mmHg). It is really important to asses C – reactive protein (CRP), procalcitonin, platelets, kreatinin and bilirubin. These factors if added duresis, evalutation of hemodynamics and PO2/FiO2mmHg could help to count SOFA score which indicates if a patient is septic or not. First choice imaging method for urosepsis is ultrasound. It is recommended to take blood and urine cultures before giving antibiotics for empirical treatment. Keywords: urosepsis, etiology, symptoms, diagnostics, treatment, qSOFA.

RSV pneumonia with or without bacterial co-infection among healthy children

Respiratory syncytial virus (RSV) is a common cause of childhood pneumonia, but there is limited understanding of whether bacterial co-infections affect clinical severity. We conducted a retrospective cohort study at National Taiwan University Hospital from 2010 to 2019 to compare clinical characteristics and outcomes between RSV with and without bacterial co-infection in children without underlying diseases, including length of hospital stay, intensive care unit (ICU) admission, ventilator use, and death. Among 620 inpatients with RSV pneumonia, the median age was 1.33 months (interquartile range, 0.67-2 years); 239 (38.6%) under 1 year old; 366 (59.0%) males; 201 (32.4%) co-infected with bacteria. The three most common bacteria are Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae. The annually seasonal analysis showed that spring and autumn were peak seasons, and September was the peak month. Compared with single RSV infection, children with bacterial co-infection were younger (p=0.021), had longer hospital stay (p<0.001), needed more ICU care (p=0.02), had higher levels of C-reactive protein (p=0.009) and more frequent hyponatremia (p=0.013). Overall, younger age, bacterial co-infection (especially S. aureus), thrombocytosis, and lower hemoglobin level were associated with the risk of requiring ICU care. RSV related bacterial co-infections were not uncommon and assoicated with ICU admission, especially for young children, and more attention should be given. For empirical antibacterial treatment, high-dose amoxicillin-clavulanic acid or ampicillin-sulbactam was recommended for non-severe cases; vancomycin and third-generation cephalosporins were suggested for critically ill patients requiring ICU care.

Treatment of severe infectious complications caused by multidrug-resistant Klebsiella pneumoniae in children with malignant neoplasms of the hematopoietic system: experience of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin Russian Cancer Research Center

Introduction. So far there has been no clear protocol on the treatment of bacterial infections in hematopoietic cancer patients undergoing polychemotherapy (PCT) and hematopoietic stem cell transplantation (HSCT). Guidelines available from antibiotic therapy panels such as EMBT, NCCN, ECIL, Sepsis-3 often fail to cover the entire spectrum of clinical risk factors of severe complications caused specifically by multiresistant Klebsiella pneumoniae.The aim of the study — is to showcase the clinical experience of demonstration of the experience of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin Russian Cancer Research Center with respect to adjusting antibacterial therapy for the spectrum of microorganisms found in the patient before the onset of antitumor therapy, and for the multiresistant microorganism findings in patients with blood cancers and febrile neutropenia (FN) undergoing PCT and HSCT.Materials and methods. The study involved five patients undergoing either PCT or HSCT for hematopoietic cancers at Research Institute of Pediatric Oncology and Hematology in October 2019 — October 2020, multiresistant Klebsiella pneumonia colonies found in each case. Results. Five patients with hematopoietic cancers and induced bone marrow aplasia were found to have multiresistant Klebsiella pneumoniae colonies on top of post-PCT/HSCT immunosuppression. Given high risk of death, these patients need early antibacterial therapy with reserve antibiotics outside standard empirical antibacterial treatment protocols should they develop FN. The Center's practices have shown that baseline protocols are often inadequate to the severity of these patients' conditions in a certain timeframe.Conclusions. To sum up the Center's limited experience, the finding is that additional research is required into the factors of risk of severe multiresistant Klebsiella pneumoniae infections in patients undergoing PCT and HSCT; algorithms must be developed for the treatment of patients in such a critical condition.

Use of ornidazole in the treatment of anaerobic infection in surgery

One of the most complex problems of modern surgery is the treatment and prevention of anaerobic infection. Main place in overcoming of this infectious complication is devoted to urgent surgical intervention and correct early empiric antibacterial therapy. Special place in the combined empiric antibacterial treatment is devoted to 5-nitroimidazoles. Modern data about clinical efficacy of ornidazole in the treatment of surgical infectious complications is presented in the article. We performed a comparison of therapeutic activity and physical-chemical properties, pharmacokinetic and pharmacodynamic features of ornidazole with the first representative of 5-nitroimidazole class – metronidazole. Taking into account antiprotozoal and antianaerobic activity of ornidazole, it is recommended to be used in the schemes of combined therapy of severe generalized anaerobic infections and purulent processes of different localization; treatment and prevention of surgical infections after intraabdominal, thoracic, proctological and dental surgical interventions.

HSV-pneumonitis in a patient with lung cancer receiving check point inhibitors \u2013 a case report

BackgroundHerpes simplex virus (HSV) is commonly associated with oro-facial and genital manifestations. It rarely causes encephalitis and even less commonly, in heavily immunosuppressed patients, visceral disease or bronchopneumonitis. We present a case of cytologically-proven, PCR-positive HSV-1 tracheobronchitis and pneumonitis in a patient with less severe immunocompromise.Case presentationA 64 year old white man with steroid-induced diabetes mellitus and progressive small-cell bronchial carcinoma despite chemo- and immunotherapy with two checkpoint inhibitors presented with symptoms of lower respiratory tract infection. Community-acquired pneumonia was suspected and empirical broad-spectrum antibacterial treatment was initiated. Chest CT-scan revealed ground-glass opacities and tree-in bud lesions. Cytology of BAL showed extensive cytopathic effects typically caused by infection with herpes virus and PCR confirmation of HSV-1. Acute phase HSV serology was positive for IgG and borderline for IgM. The patient deteriorated clinically due to tumor progress and infection despite high-dose acyclovir therapy and died 2 weeks after admission.ConclusionsWe report an unusual case of fatal HSV-1 pneumonitis due to reactivation in a patient with lung cancer, steroid-induced diabetes and treatment with two checkpoint inhibitors. In immunosuppressed patients with non-improving pneumonia invasive diagnostic procedures are warranted including cytology and molecular diagnostics.

COVID-19 management in heart transplanted recipients: registry of Almazov National Medical Research Centre.

Aim This study presents the experience of managing patients with COVID-19 after cardiac transplantation (CT).Material and methods Infectious complications (IC) following CT are a leading cause for morbidity and mortality. A prolonged incubation period, atypical IC symptoms, and originally altered results of laboratory and instrumental diagnosis are characteristic of recipients due to immunosuppression. In 2020, the coronavirus infection (COVID-19) rapidly spread worldwide, and timely diagnosis and searching for effective treatments for this disease became a major challenge. From January 2010 through July 2020, 148 patients received orthotopic heart transplants at the V.A. Almazov National Medical Research Center; 34 of these patients died by the present time and were excluded from this analysis. 114 patients were included into the retrospective evaluation of results. These patients had been a part of the group followed up at the Center for more than a month.Results From March through July 2020, 12 (10.5 %) of 114 CT recipients were infected with the virus SARS-CoV-2. In 75 % (n=9) of the sick patients, the COVID-19 infection developed after more than one year after CT. From the first day of clinical symptoms, mycophenolic acid/everolimus were temporarily suspended. The outpatient treatment was started on the first day and included an antiviral therapy (oseltamivir), mucolytics (bromhexine), vitamin C, and anticoagulants. If the disease onset was associated with pyretic fever the empiric antibacterial levofloxacin treatment was administered due to a high risk of mixed infection. Hospitalized patients with moderately severe COVID-19 (n=3) were treated with oxygen inhalation through nasal cannula and prone position with a positive effect.Conclusion Remote counseling of patients after CT and consistency of the outpatient treatment with recommendations of managing transplant physicians provided timely diagnosis of IC, early administration of treatment, and the absence of COVID-19 complications. Reducing the regimen of immunosuppressive therapy (antiproliferative agents) for up to 14 days facilitated infection control and was not associated with acute rejection crisis and/or impairment of the transplant function.

Role of antibiotics in coronavirus 2019

During the current COVID-19 pandemic, there are potential threats that could affect antimicrobial stewardship activities and drive antimicrobial resistance. For instance, many individuals presenting with mild disease without pneumonia or moderate disease with pneumonia receive antibiotics. Zhou et al. [5] showed that in the current coronavirus disease 2019 (COVID-19) pandemic, 50% of patients with COVID-19 who have died had secondary bacterial infections. Rapid characterization of coinfection is essential. It will save lives. Notably, among COVID-19 ICU cases in Zhongnan Hospital, there was a high reported frequency of secondary infections with carbapenem-resistant Acinetobacter baumannii, particularly among ICU deaths. The standard empiric antibacterial treatment should be initially prescribed for adults with clinical and radiographic evidence of CAP who test positive in the inpatient and outpatient settings. If hydroxychloroquine is being used for COVID-19 treatment, avoid antibiotics that also prolong QTc interval (e.g. levofloxacin, azithromycin).

Detection and Control of Biofilm Formation by Staphylococcus aureus from Febrile Neutropenic Patient.

IntroductionFebrile neutropenia (FN) is the evolution of fever in a patient with neutropenia over 38.0°C. Neutropenia is diagnosed when absolute neutrophil count (ANC) <1500 cells/µL. FN represents a common complication of cancer treatment. Hence, it is featured to be a major cause of morbidity and mortality in cancer patients. Staphylococcus aureus is one of the most important microorganisms isolated from the blood of febrile neutropenic patients. Infections caused by S. aureus range from mild to life-threatening diseases. Biofilm production by S. aureus is one of the most significant virulence factors of the bacterium as it prevents the penetration of antibiotics. Recently, it has been shown that S. aureus carries the ica operon responsible for biofilm production. The aim of the work is to determine a genotypic characterization that includes not only the detection of icaA and icaD genes in S. aureus but also the determination of their relation to clinical and microbiological features. Empiric antibacterial treatment was recommended for cancer patients receiving chemotherapy.Materials and MethodsThe relation between the presence of icaA and icaD and biofilm production was determined in a collection of 66 S. aureus samples from febrile neutropenic patients. Biofilm-forming ability was tested on Congo Red agar plates. Also, the effect of the most sensitive antibiotics on the bacterial cells was determined by an electron microscope.ResultsOf the bacterial samples, 48 were biofilm-productive and 18 were non-biofilm productive. For the biofilm productive bacteria, 37.5% were positive for icaA, 22.9% were positive for icaD and 10.4% were positive for both. Linezolid was the most effective antibiotic and it is highly recommended for the treatment of febrile neutropenia caused by biofilm-productive S. aureus. Severe changes were found on the bacterial cell after being treated with Linezolid. The icaA and icaD genes were present in only 50% of biofilm-productive bacteria.ConclusionThe ica operon is present in only 50% of biofilm-productive S. aureus and Linezolid is the best antibiotic against these bacteria.

Infections of the lungs in returning travellers

Auf Auslandsreisen kann es zu Infektionen mit Erregern kommen, die in Deutschland nicht endemisch sind. Vor dem Hintergrund einer stetig zunehmenden Reiseaktivität der Bevölkerung gewinnen diese Infektionen bei Reiserückkehrern an Bedeutung. Ältere und vorerkrankte Reisende stellen dabei eine besondere Risikogruppe dar. Die Kenntnis von im Ausland vorkommenden Erregern und typischen Krankheitsbildern ist essenziell, um eine entsprechende Verdachtsdiagnose stellen zu können, insbesondere bei Patienten, bei denen eine erste kalkulierte antibakterielle Therapie ohne Effekt bleibt. Die Erhebung einer detaillierten Reiseanamnese ist entscheidend, um Aufschluss über eine mögliche Exposition gegenüber spezifischen Erregern zu gewinnen und die korrekte Diagnostik in die Wege leiten zu können. Neben Erregern, die primär zu einer Infektion der Lunge führen, müssen differenzialdiagnostisch auch immer nichtpulmonale Infektionen mit einer pulmonalen Begleitsymptomatik, wie beispielsweise Schistosomiasis oder Malaria, in Betracht gezogen werden. Zwei Beispiele von pulmonalen Infektionen, die ausschließlich im Ausland erworben werden können, sind die Melioidose und die Kokzidioidomykose. Während eine pulmonale Manifestation der Melioidose akut und fulminant verlaufen und mit einer hohen Letalität assoziiert sein kann, ist die Kokzidioidomykose primär meist oligosymptomatisch, mit erheblicher Latenz können jedoch pulmonale Manifestationen auftreten, die in ihrer Vielfalt der Tuberkulose oder Malignomen ähneln können.

Carbapenemase-Producing Enterobacteriaceae (CPE) Bloodstream Infections (BSI) in Neutropenic Patients (pts) with Acute Leukemia (AL). Comparison of 2 Strategies

Introduction. The global increase in CPE infections is probably the strongest threat to the success of AL therapy nowadays. CP-K.pneumoniae (CP-Kp) BSI in particular have a high mortality in neutropenic pts, tend to reappear in subsequent courses and lead to delays in chemotherapy (CT). To make things worse, no effective decolonization is available, isolation measures are controversial, and optimal treatment is largely unknown. The widespread use and abuse of carbapenems perpetuate the problem. An outbreak of CP-Kp BSI began in our center in Nov/16, leading to profound changes in empirical and directed antibacterial protocols. This report analyzes the impact of these modifications on clinical outcomes. Methods. Until Feb/18, our empirical regimen for a first neutropenic fever was monotherapy with meropenem; for documented CP-Kp BSI a double or triple combination, including colistin, tigecycline, high-dose/prolonged infusion meropenem or an aminoglycoside, was selected according to MICs. Since Mar/18 empirical carbapenems were banned, and a new empirical strategy was implemented: pts who were not colonized (rectal swab screening at started Sept/17) received piperacillin-tazobactam; known colonized pts received colistin + tigecycline. This regimen was modified 48h later on the basis of blood culture results, with de-escalation (if no growth of CP-Kp) versus immediate prescription of ceftazidime-avibactam (CF-A) which was given even for colistin-susceptible strains, with the dual intention of reducing nephrotoxicity and delaying resistance to colistin. Univariate analysis was performed to identify factors related to mortality, using the χ2 test and Fisher's exact test. Results. From Nov/16 to Aug/18, 54 consecutive CP-Kp BSI were documented in 45 pts (9 pts surviving a first episode developed a new one in a later CT course). Of note, 3 of these 54 BSI occurred in 2016 (1% of all BSI and 4% of Kp BSI that year), 32 in 2017 (11% and 38%, respectively), and 19 in 2018 until August (13% and 32%). Median age of pts was 58 (17-85), 34 were male, and hospitalization was mainly intended for induction (74%) or consolidation (18%) cycles. Median duration of neutropenia &amp;lt; 500/μl at the onset of bacteremia was 7 days (0-74). A clinical source was identified in most pts: pneumonia in 26%, soft tissue infection in 22%, enterocolitis in 17%. Of the 30 episodes registered since screening began, 16 occurred in colonized patients (11 with KPC, 5 OXA-48). Septic shock developed in 41% of the episodes, and ICU admission was necessary in 30%. In 19 episodes (35%) empirical antibacterial treatment was (retrospectively) considered appropriate if it had included colistin and/or tigecycline. CF-A was prescribed as directed therapy in 28 cases (52%). Microbiological cure (negative blood cultures) was verified in 86% of 49 evaluable episodes. Attributable mortality (due to this infection) at day 14 of the onset of bacteremia was 22% (12 cases) and global mortality during hospitalization was 31% (17 cases). Fifteen of these 17 deaths occurred in the 40 episodes registered before protocol modification in Mar/18 and only 2 in the 14 episodes after that date (37% vs 14%). Adverse outcomes were significantly related to unresolved bacteremia, to occurrence of septic shock and to ICU admission (all p&amp;lt;0.001). Survival was more likely if microbiological cure was achieved (p&amp;lt;0.001), if appropriate antibiotics were empirically given at the onset of fever, and if directed treatment consisted of CF-A (p=0.02). Conclusions. In this series of profoundly neutropenic pts under intensive CT, the mortality rate from CP-Kp BSI was very high. Unresolved neutropenia and severity of the infection itself (as measured by the presence of septic shock and/or ICU admission) had, as expected, a major impact on death. Two treatment-related factors (time to appropriate empirical coverage and directed use of CF-A) had a major influence on survival, both presumably through faster microbiological resolution. The strategy we implemented has two aims: allowing appropriate and timely empirical coverage in colonized patients while sparing carbapenems, and optimizing directed therapy while reducing colistin use and toxicity. Although the present data need confirmation in a larger series, we believe that the recent sharp decrease in mortality observed in our pts with CP-Kp bacteremia stems from these measures. Disclosures No relevant conflicts of interest to declare.

2187. Prediction of Patient Outcome During Febrile Neutropenia Despite Anti-infective Treatment Using Machine Learning Algorithms

BackgroundClinical management of prolonged febrile neutropenia despite broad-spectrum empirical antibacterial treatment is a clinical challenge, as standard empirical treatment has failed and a broad spectrum of differential diagnoses has to be considered. Growing prevalence of multi-resistant bacteria and fungi has made a balanced choice of effective anti-infective treatment more difficult. A reliable prediction of complications could indicate options for treatment optimization.MethodsWe implemented a supervised machine learning approach to predict death or admission to intensive care unit within 28 days in cancer patients with prolonged febrile neutropenia (neutrophils < 500/mm3 and body temperature ≥ 38°C longer than 3 days). We analyzed highly granular retrospective medical data of the Cologne Cohort of Neutropenic Patients (CoCoNut) between 2008 and 2014. Random forest and 10-fold cross-validation were used for classification. The neutropenic episodes from 2014 were used for evaluation of prediction.ResultsIn total, 927 episodes of prolonged febrile neutropenia (median age 52 years, interquartile range 42–62; 562/927 [61%] male; 390/927 [42%] acute myeloid leukemia; 297/927 [32%] lymphoma) with 211/927 (23%) adverse outcomes were processed. We computed 226 features including patient characteristics, medication, clinical signs, as well as laboratory results describing changes of state and interactions of medical parameters. Feature selection revealed 65 features with an area under the receiver operating characteristic curve (AUC) of 0.75. In the validation data set the optimized model had a sensitivity/specificity of 36% and 99% (AUC: 0.68; misclassification error: 0.12) and positive/negative predictive values of 89% and 88%, respectively. The most important features were albumin, age, and procalcitonin.ConclusionStructured granular medical data and machine learning approaches are an innovative tool that can be used in a retrospective setting for prediction of adverse outcomes in patients with prolonged febrile neutropenia. This study is the first important step toward clinical decision support based on predictive models in high-risk cancer patients.Disclosures All authors: No reported disclosures.