Adequate Antibiotic Therapy Research Articles

LTT-Validity in diagnosis and therapeutical decision making of neuroborreliosis: a prospective dual-centre study.

The key objective of this study was to assess the validity of a commercially available in-house Lymphocyte Transformation Test (LTT) as a diagnostic parameter and indicator of disease activity/therapeutic efficacy in the context of Lyme neuroborreliosis (LNB). A prospective dual-centre study was conducted from 05/14 - 01/18. With respect to Borrelia-LTT a comparison was made between patients suffering from confirmed acute LNB and patients being affected by inflammatory neurologic diseases, defining the control group: Bell's palsy, viral meningitis, herpes zoster, Guillain-Barré-Syndrome and Encephalomyelitis disseminate. Furthermore, we investigated the LTT within the LNB group at the time of admission and again 12 weeks (+/- one week) later - after appropriate antibiotic treatment. Cases included 15 patients with LNB and 58 participants in the control group. With regard to Borrelia-LTT we calculated a low sensitivity of 40% and a moderate specificity of 91% for LNB. Additionally, LTT-levels three months after adequate antibiotic therapy did not correlate with the therapeutic response of LNB patients. The present study shows that LTT is neither appropriate for LNB detection nor suitable as a follow-up marker.

Unraveling the Narrative of Orbital Cellulitis as a Sequelae to Trauma

Abstract Orbital cellulitis is often seen as a serious complication of acute rhinosinusitis. Facial trauma is one of the possible causes of orbital cellulitis. A middle-aged man, a mason by occupation, presented to ENT OPD following a facial trauma. He presented with a laceration over the right zygomatic region with right-sided periorbital swelling and redness. Wide-spectrum antibiotics were initiated for the patient. Pus was drained daily, and surgical debridement of the wound followed by sterile dressing of the wound cavity was done regularly until the pus discharge totally stopped. The patient was taken for secondary suturing and was discharged after that. However, the patient lost to follow-up. Facial trauma is a cause of orbital cellulitis. Orbital cellulitis is an emergency condition and requires urgent medical attention. Adequate antibiotic therapy is of utmost importance to treat the condition. Surgical care is advisable if the medical line of management fails.

PhoPQ-mediated lipopolysaccharide modification governs intrinsic resistance to tetracycline and glycylcycline antibiotics in Escherichia coli.

Elucidating the resistance mechanisms of clinically important antibiotics helps in maintaining the clinical efficacy of antibiotics and in the prescription of adequate antibiotic therapy. Although tetracycline and glycylcycline antibiotics are clinically important in combating multidrug-resistant Gram-negative bacterial infections, their mechanisms of resistance are not fully understood. Our research demonstrates that the E. coli PhoPQ two-component system affects resistance to tetracycline and glycylcycline antibiotics by controlling the expression of phosphoethanolamine transferase EptB, which catalyzes the modification of the inner core residue of lipopolysaccharide (LPS). Therefore, our findings highlight a novel resistance mechanism to tetracycline and glycylcycline antibiotics and the physiological significance of LPS core modification in E. coli.

Effect of adequacy of empirical antibiotic therapy for hospital-acquired bloodstream infections on intensive care unit patient prognosis: a causal inference approach using data from the Eurobact2 study

ObjectivesHospital-acquired bloodstream infections (HA-BSI) in the intensive care unit (ICU) are common life-threatening events. We aimed to investigate the association between early adequate antibiotic therapy and 28-day mortality in ICU patients who survived at least 1 day after the onset of HA-BSI. MethodsWe used individual data from a prospective, observational, multicentre, and intercontinental cohort study (Eurobact2). We included patients who were followed for ≥1 day and for whom time-to-appropriate treatment was available. We used an adjusted frailty Cox proportional-hazard model to assess the effect of time-to-treatment-adequacy on 28-day mortality. Infection- and patient-related variables identified as confounders by the Directed Acyclic Graph were used for adjustment. Adequate therapy within 24 hours was used for the primary analysis. Secondary analyses were performed for adequate therapy within 48 and 72 hours and for identified patient subgroups. ResultsAmong the 2418 patients included in 330 centres worldwide, 28-day mortality was 32.8% (n = 402/1226) in patients who were adequately treated within 24 hours after HA-BSI onset and 40% (n = 477/1192) in inadequately treated patients (p < 0.01). Adequacy within 24 hours was more common in young, immunosuppressed patients, and with HA-BSI due to Gram-negative pathogens. Antimicrobial adequacy was significantly associated with 28-day survival (adjusted Hazard Ratio (aHR), 0.83; 95% CI, 0.72–0.96; p 0.01). The estimated population attributable fraction of 28-day mortality of inadequate therapy was 9.15% (95% CI, 1.9–16.2%). DiscussionIn patients with HA-BSI admitted to the ICU, the population attributable fraction of 28-day mortality of inadequate therapy within 24 hours was 9.15%. This estimate should be used when hypothesizing the possible benefit of any intervention aiming at reducing the time-to-appropriate antimicrobial therapy in HA-BSI.

Performance and impact of rapid multiplex PCR on diagnosis and treatment of ventilated hospital-acquired pneumonia in patients with extended-spectrum β-lactamase-producing Enterobacterales rectal carriage

BackgroundAntimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including blaCTX-M, the most common ESBL-encoding gene.MethodsThis monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP.ResultsOver the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: blaCTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and blaCTX-M were concordant in 35/41 (85%) episodes, and in all episodes where blaCTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1–35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6–22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5–22.1), p = 0.01).ConclusionmPCR blaCTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted.

Gentamicin combination treatment is associated with lower mortality in patients with invasive listeriosis: a retrospective analysis.

Listeria monocytogenes causes severe bacterial infections with the highest mortality rate among foodborne pathogens in Europe. Combination treatment with ampicillin and gentamicin is recommended for invasive manifestations. However, evidence to support this treatment approach remains limited due to a lack of randomised controlled trials. To explore this critical issue further, we conducted this retrospective, single-center study. We identified all patients hospitalized with invasive listeriosis at the University Medical Center Hamburg-Eppendorf between 2009 and 2020 and analyzed the effect of gentamicin combination treatment versus monotherapy on 90-day mortality. In total, 36 patients with invasive listeriosis were included, of which 21 patients received gentamicin combination treatment and 15 received monotherapy. The mean age-adjusted Charlson Comorbidity Index (aaCCI) value was lower in the gentamicin combination treatment group (5.4 vs. 7.4). Neurolisteriosis was more common in the gentamicin group (81% vs. 20%). The 90-day mortality was with significantly lower in the gentamicin combination treatment group (10%) compared to the monotherapy group (60%). Multivariable cox regression analysis, adjusted for a propensity score computed based on neurolisteriosis, aaCCI and sex, revealed a significantly reduced hazard ratio of 0.07 (95% CI: 0.01-0.53, p = 0.01) for 90-day mortality for the gentamicin combination treatment. This retrospective study highlights the benefit of gentamicin combination treatment in reducing the 90-day mortality rate among patients with invasive listeriosis. The high prevalence of monotherapy in this study cohort raises concerns about the adequacy of antibiotic therapy in clinical practice.

BRULURE CUTANEE CHEZ LES ENFANTS : ASPECTS CLINIQUES ET THERAPEUTIQUES DANS LE SERVICE DE CHIRURGIE GENERALE DE L’HOPITAL IGNACE DEEN CHU DE CONAKRY.

A burn is an injury to the skin covering and underlying structures caused by a thermal, electrical, radioactive or chemical agent. Objective: To study the clinical and therapeutic aspects of childhood skin burns in a Conakry university hospital. Methodology: This is a 4-year retrospective descriptive study from January 2018 to December 2021. We identified 55 burn patients. The average age was 3.16±2.85 years. The male gender was the most affected (n=33; 60%). Results: The burns were thermal in 80% of cases, hot liquid was the dominant causal agent with 85.45% of cases. We observed a dominance of second degree burns in 85% of cases. These burns were accidental in 100% of cases and occurred at home in 84% of cases. Treatment was medical and combined rehydration, antibiotic therapy and analgesia. Trimming and/or dressing was performed under general anesthesia for 26 patients (34.6%). A discharge aponeurotomy on the forearms wasperformed in 2 patients or 2.6% of cases. The evolution was favorable in 72.7% of cases. Seven children died Conclusion: Childhood burns occur at home and are mainly caused by thermal liquids. Clinically, it mainly causes second-degree lesions. Its treatment is medical and based on good rehydration associated with adequate antibiotic therapy and analgesia. Surgical care involves trimming and aponeurotomy. Keywords: burn, child, thermal agent, medical treatment

#1814 Infection associated pancreatitis in peritoneal dialysis, a case report

Abstract Background and Aims Peritoneal dialysis (PD) patients seem to have a higher incidence of acute alithiasic pancreatitis. Though rare and with some suggested triggers described in the literature, this is still a poorly understood and potentially life-threatening complication. We present a 60 years old woman concluding antimicrobial therapy with an icodextrin night-dwell regimen for peritonitis presenting with epigastric pain. This work reviews our approach to cloudy effluent from non-infectious causes during an infection while managing acute pancreatitis in the PD setting. We report diagnostic difficulties and treatment considerations with a positive outcome. Method We present a 60 years old woman on PD for one year presenting to the emergency room in November of 2023 with severe epigastric pain, nausea and emesis. She suffered from stage 5 chronic kidney disease due to autosomal dominant polycystic kidney disease and had disease complications as anemia and secondary hyperthyroidism controlled within targets. She was on automated PD (APD) with glucose based solutions. She was on the 17th of 21 days antibiogram guided treatment (ceftazidime) for a Enterobacter ludwigii PD-related peritonitis with good clinical evolution and peritoneal effluent (PE) leukocyte count per μl from 1258 to 91 in 5 days. In the previous 3 months she had had 2 other infectious episodes. A bacteremic urinary tract infection to E. coli associated with peritonitis treated with antibiogram guided therapy (ceftazidime) followed by C. difficile colitis treated with oral vancomycin. During each infection period she transitioned from APD to continuous ambulatory peritoneal dialysis with an icodextrin night dwell. On admission she presented with normal vital signs, no fever, and abdominal distention with severe epigastric tenderness to palpation without muscular guarding. Her dwell exchange showed blood-tinged cloudy PE. She had hemoglobin of 11.3 g/dl, otherwise normal blood cell counts, and raised amylase (213 UI/l) and lipase (1467 UI/l). There was no elevation of transaminases, cholestatic enzymes, C-reactive protein or procalcitonin and lipidemia or hyperbilirubinemia were normal. PE cell count showed 213/μl leukocytes and 202/μl erythrocytes. Abdominal ultrasound showed no evidence of an obstructive cause. She was admitted in the surgical care unit for a conservative and watchful approach. Results On presentation we accounted for the peritonitis still under treatment, acute pancreatitis, drug therapy and recently introduced icodextrin solution. The acute alithiasic pancreatitis diagnosis was established but there was still a possible causative role of icodextrin or infection and refractory peritonitis could also not be promptly excluded. The literature suggests icodextrin and other drugs as causes for acute pancreatitis in some patients but also mentions the possibility of cloudy or hemorrhagic effluent due to abdominal inflammation processes. Considering the clinical stability, the multiple possible contributing causative agents and the differential diagnosis of refractory peritonitis we closely monitored PE cell count evolution keeping the icodextrin dwell and ceftazidime prescriptions and collected samples for bacterial and fungal culture. The cultures were negative and stability of leukocyte count and mononuclear cell predominance (Fig. 1) helped us exclude the peritonitis hypothesis and attribute the PE changes to the pancreatitis process. Conclusion Inpatient monitoring and identifying all possible causes are essential to ensure good outcomes in PD patients suffering from acute pancreatitis. Full anamnesis, physical examination and close attention to laboratory findings were key in allowing adequate antibiotic therapy and resolution of the abdominal inflammatory process at hand while maintaining an adequate PD prescription.

Community-acquired Klebsiella pneumoniae pneumonia in ICU: a multicenter retrospective study

BackgroundAlongside the recent worldwide expansion of hypervirulent Klebsiella pneumoniae (KP) infections, the available literature regarding cases of community acquired pneumonias (KP-CAP) remains scarce but reports a strikingly high and early mortality. We performed a retrospective multicenter study (7 ICU in France) between 2015 and 2019, comparing prognosis and severity of KP-CAP versus Streptococcus pneumoniae - CAP (SP-CAP).MethodsFor each KP-CAP, three SP-CAP admitted in ICUs within the same center and within the same 6-month window were selected. When available, KP strains were studied, and bacterial virulence was genetically assessed for virulence factors. The primary outcome was in-hospital mortality. Associations between clinical outcomes and type of infection were tested using univariate and multivariate logistic regressions, adjusted for pairing variables.ResultsTwenty-seven KP-CAP and 81 SP-CAP were included. Respective in-hospital mortality rates were 59% (n = 16) and 17% (n = 14, p < 0.001), despite adequate antibiotic therapy. KP-CAP median time from admission to death was 26.9 h [IQR 5.75–44 h] and were significantly associated with higher rates of multiple organ failures (93% vs. 42%, p < 0.001), disseminated intravascular coagulation (12% vs. 1.3%, p = 0.046), septic shock (median lactate on ICU admission 4.60 vs. 2.90 mmol/L, p = 0.030) and kidney failure (KDIGO-3: 87% vs. 44%, p < 0.001). Interestingly, alcoholism was the only identified predisposing factor of KP-CAP. Severity on ICU admission (2-fold higher for KP-CAP) was the only factor associated with mortality in a multivariate analysis.ConclusionWe described a strong association between KP-CAP infection and higher and earlier mortality when compared to SP-CAP. Moreover, alcoholism was the sole predisposing factor associated with KP-CAP infection. These findings should raise awareness of clinicians involved in the management of severe CAP about this microbiological etiology. Future prospective studies are needed to confirm these results and to design strategies to improve the prognosis of such infections.

Risk Factors and Scoring Systems to Predict the Mortality Risk of Afebrile Adult Patients with Monomicrobial Gram-Negative Bacteremia: A 10-Year Observational Study in the Emergency Department.

The mortality rate of afebrile bacteremia has been reported to be as high as 45%. This investigation focused on the risk factors and predictive performance of scoring systems for the clinical outcomes of afebrile patients with monomicrobial gram-negative bacteria (GNB) in the emergency department (ED). We conducted a retrospective analysis of afebrile adult ED patients with monomicrobial GNB bacteremia from January 2012 to December 2021. We dissected the demographics, clinical pictures, and laboratory investigations. We applied five scoring systems and three revised systems to predict the clinical outcomes. There were 600 patients included (358 males and 242 females), with a mean age of 69.6 ± 15.4 years. The overall mortality rate was 50.17%, reaching 68.52% (74/108) in cirrhotic patients. Escherichia coli was the leading pathogen (42.83%). The non-survivors had higher scores of the original MEDS (p < 0.001), NEWS (p < 0.001), MEWS (p < 0.001), qSOFA (p < 0.001), and REMS (p = 0.030). In univariate logistic regression analyses, several risk factors had a higher odds ratio (OR) for mortality, including liver cirrhosis (OR 2.541, p < 0.001), malignancy (OR 2.259, p < 0.001), septic shock (OR 2.077, p = 0.002), and male gender (OR 0.535, p < 0.001). The MEDS demonstrated that the best predictive power with the maximum area under the curve (AUC) was measured at 0.773 at the cut-off point of 11. The AUCs of the original NEWS, MEWS, qSOFA, and REMS were 0.663, 0.584, 0.572, and 0.553, respectively. We revised the original MEDS, NEWS, and qSOFA by adding red cell distribution width, albumin, and lactate scores and found a better predictive power of the AUC of 0.797, 0.719, and 0.694 on the revised MEDS ≥11, revised qSOFA ≥ 3, and revised NEWS ≥ 6, respectively. The original MEDS, revised MEDS, revised qSOFA, and revised NEWS were valuable tools for predicting the mortality risk in afebrile patients with monomicrobial GNB bacteremia. We suggested that clinicians should explore patients with the risk factors mentioned above for possible severe infection, even in the absence of fever and initiate hemodynamic support and early adequate antibiotic therapy in patients with higher scores of the original MEDS (≥11), revised MEDS (≥11), revised NEWS (≥6), and revised qSOFA (≥3).

Development of a multiplex real-time PCR assay for simultaneous detection of common colistin and carbapenemase genes

Carbapenem and colistin are often used as last-resort treatment for Gram-negative multi-drug resistant (MDR) bacteria. Nevertheless, co-resistance of these drugs is threatening the global healthcare system. Rapid and accurate detection of carbapenem and colistin resistant bacteria is critical for adequate antibiotic therapy and infection control, particularly in the context of an outbreak. The presence of blaNDM, blaKPC, blaIMP-1 and blaOXA-48 is responsible for greater than 95% phenotypic resistance in carbapenem-resistant Enterobacteriaceae, while mcr-1 is the most prevalent and well disseminated of all mcr genes in colistin-resistant strains. In this study, we aim to develop a multiplex real time-PCR assay for simultaneous detection of the five genes blaNDM, blaKPC, blaIMP-1, blaOXA-48 and mcr-1. The melting curve-based multiplex real time PCR assay was established with the dissociation temperature range extended from 76°C to 87°C. The whole process is completed within one hour and half, allowing rapid screening of the five genes in cultured bacteria samples with a limit of detection of 10 CFU/ml. The proposed multiplex real-time PCR assay is a robust, reliable and rapid method for the detection of bacterial strains carrying blaOXA-48, blaIMP, blaNDM, blaKPC and mcr-1 gene individually or in cocktail of genes. This assay will be a valuable tool for surveillance and monitoring of MDR bacteria additionally resistant to either carbapenem or colistin or both drugs.

Next-generation microbiological testing in intraabdominal infections with PCR technology

PurposeIntraabdominal infections (IAI) are increasing worldwide and are a major contributor to morbidity and mortality. Among IAI, the number of multi-drug resistant organisms (MDRO) is increasing globally. We tested the Unyvero A50® for intraabdominal infections, compared the detected microorganisms and antibiotic resistance, and compared the results with those of routine microbiology.MethodsWe prospectively compared samples obtained from surgical patients using PCR-based Unyvero IAI cartridges against routine microbiology for the detection of microorganisms. Additionally, we identified clinical parameters that correlated with the microbiological findings. Data were analyzed using the t-test and Mann–Whitney U test.ResultsSixty-two samples were analyzed. The PCR system identified more microorganisms, mostly Bacteroides species, Escherichia coli, and Enterococcus spp. For bacterial resistance, the PCR system results were fully concordant with those of routine microbiology, resulting in a sensitivity, specificity, and positive and negative predictive value (PPV, NPV) of 100%. The sensitivity, specificity, PPV, and NPV for the detection of microorganisms were 74%, 58%, 60%, and 72%, respectively. CRP levels were significantly higher in patients with detectable microorganisms. We identified more microorganisms and bacterial resistance in hospital-acquired intra-abdominal infections by using the PCR system.DiscussionIAI warrants early identification of the microorganisms involved and their resistance to allow for adequate antibiotic therapy. PCR systems enable physicians to rapidly adjust their antibiotic treatment. Conventional microbiological culture and testing remain essential for determining the minimal growth inhibition concentrations for antibiotic therapy.

Clinical spectrum and long-term outcomes of mpox: a cohort study spanning from acute infection to six-month follow-up

BackgroundCases of mpox have been reported worldwide since May 2022. Limited knowledge exists regarding the long-term course of this disease. To assess sequelae in terms of scarring and quality of life (QoL) in mpox patients 4–6 months after initial infection.MethodsProspective observational study on clinical characteristics and symptoms of patients with polymerase chain reaction (PCR)-confirmed mpox, including both outpatients and inpatients. Follow-up visits were conducted at 4–6 months, assessing the Patient and Observer Scar Assessment Scale (POSAS), the Dermatology Life Quality Index (DLQI) and sexual impairment, using a numeric rating scale (NRS) from 0 to 10.ResultsForty-three patients, age range 19–64 years, 41 men (all identifying as MSM) and 2 women, were included. Upon diagnosis, skin or mucosal lesions were present in 93.0% of cases, with 73.3% reporting pain (median intensity: 8, Q1-Q3: 6–10). Anal involvement resulted in a significantly higher frequency of pain than genital lesions (RR: 3.60, 95%-CI: 1.48–8.74). Inpatient treatment due to pain, superinfection, abscess or other indications was required in 20 patients (46.5%). After 4–6 months, most patients did not have significant limitations, scars or pain. However, compared to patients without such complications, patients with superinfection or abscess during the acute phase had significantly more extensive scar formation (median PSAS: 24.0 vs. 11.0, p = 0.039) and experienced a significantly greater impairment of their QoL (median DLQI: 2.0 vs. 0.0, p = 0.036) and sexuality (median NRS: 5.0 vs. 0.0, p = 0.017).ConclusionWe observed a wide range of clinical mpox manifestations, with some patients experiencing significant pain and requiring hospitalization. After 4–6 months, most patients recovered without significant sequelae, but those with abscesses or superinfections during the initial infection experienced a significant reduction in QoL and sexuality. Adequate treatment, including antiseptic and antibiotic therapy during the acute phase, may help prevent such complications, and hence, improve long-term outcomes.

A case report of left circumflex stent infection and mycotic aneurysm: a rare but life-threatening complication of percutaneous coronary intervention

BackgroundCoronary stent infections are an uncommon but deadly complication of percutaneous coronary intervention. Mortality remains as high as 40–60% even with adequate treatment. We report such an interesting case of left circumflex stent (LCX) infection and mycotic aneurysm that was successfully managed with antibiotics and surgery.Case presentationA middle-aged man who underwent percutaneous coronary intervention (PCI) to the left circumflex artery four weeks prior was referred as a case of pyrexia of unknown origin, not responding to antibiotics, and colchicine started for suspected Dressler syndrome. Although the inflammatory markers were elevated, the results of the blood culture did not show any growth. Echocardiography showed a doubtful echogenic structure in the left atrioventricular groove and mild pericardial effusion, and a stent infection was suspected. PET scan showed focal metabolic activity in the region of the LCX stent, with metabolically active supraclavicular and paratracheal lymph nodes, and a coronary angiogram revealed an aneurysm arising distal to the stented LCX. A diagnosis of stent infection and associated mycotic aneurysm was made, and the patient underwent surgery which included aneurysm repair, stent retrieval, and coronary artery bypass graft (CABG) to the major and terminal OM. The postoperative course was uneventful, and the patient was discharged without complications.ConclusionsIt is important to investigate the possibility of coronary stent infection in individuals experiencing prolonged fever following PCI. PET scans and coronary angiograms can aid in diagnosis when echocardiograms are inconclusive. Adequate antibiotic therapy and timely surgery are crucial for successfully managing coronary stent infections.

Carbapenemase Detection and Identification: Which method should be Chosen?

Carbapenemase production constitutes the key mechanism of resistance to carbapenems. Rapid detection or confirmation of the involvement of carbapenemase-producing bacteria (CPB) in infections is crucial for adequate antibiotic therapy and infection control, particularly during epidemics or for surveillance purposes. The Ambler classification proposes four classes of carbapenemases: classes A, B, C, and D. Carbapenemases A, C, and D are called serine carbapenemases because they use serine in their active site to catalyze the hydrolysis of carbapenems. Class B carbapenemases are metallo-beta-lactamases (MBLs) that use a cation (Zn2+) to hydrolyze the beta-lactam ring. Biochemical, chromogenic, immunochromatographic, mass spectrometric, and molecular methods have both advantages and limitations for carbapenemase detection. Although there is no single method that meets all specifications of an ideal test, it is important to explore methods to identify the most suitable ones. Thus, according to the research articles reported in this review and the criteria (cost, turnaround time, sensitivity, specificity, expertise needs, target carbapenemases), chromogenic tests such as ChromID CARBA SMART and CHROMagar™ mSuperCARBA™ would be the best candidates for the rapid and effective detection of carbapenemase-producing bacteria in developing countries. Moreover, Carba NP, SUPERCARBA and Carbapenem Inactivation Method (CIM) could also be considered good carbapenemase-detecting methods. WGS may be reserved for large-scale funded studies of carbapenemase-producing bacteria.

Corticosteroids in sepsis and community-acquired pneumonia.

Sepsis and septic shock, which are often caused by pneumonia, impact millions of people every year. Despite adequate antibiotic therapy, mortality remains high, up to 45% in septic shock, which is characterized by an inappropriate, excessive immune response of the host. Moreover, critical illness-related corticosteroid insufficiency often coexists. Against this background, several trials and meta-analyses evaluated corticosteroid therapy as adjuvant therapy with heterogeneous results. Indeed, before 2000, high-dosage, short courses of corticosteroid treatment resulted in no benefit on mortality and ahigher rate of adverse events. After 2000, thanks to adeeper understanding of the pathophysiology, low-dosage with longer courses of treatment were tested. With this regimen, afaster decrease in inflammation and faster resolution of shock, with alow rate of mild adverse events, was demonstrated although no clear effect on mortality was shown. To date, guidelines on sepsis and septic shock and guidelines on severe community-acquired pneumonia suggest corticosteroid use in selected patients. Furthermore, by utilizing latent class analysis, phenotypes of sepsis patients who benefit the most from corticosteroid treatment were recently identified. Future research should be guided by aprecision medicine approach to identify adequate dosage and duration of corticosteroid treatment for appropriate patients. This article is freely available.

Machine learning model for the prediction of gram-positive and gram-negative bacterial bloodstream infection based on routine laboratory parameters

BackgroundBacterial bloodstream infection is responsible for the majority of cases of sepsis and septic shock. Early recognition of the causative pathogen is pivotal for administration of adequate empiric antibiotic therapy and for the survival of the patients. In this study, we developed a feasible machine learning (ML) model to predict gram-positive and gram-negative bacteremia based on routine laboratory parameters.MethodsData for 2118 patients with bacteremia were obtained from the Medical Information Mart for Intensive Care dataset. Patients were randomly split into the training set and test set by stratified sampling, and 374 routine laboratory blood test variables were retrieved. Variables with missing values in more than 40% of the patients were excluded. Pearson correlation test was employed to eliminate redundant features. Five ML algorithms were used to build the model based on the selected features. Additionally, 132 patients with bacteremia who were treated at Qilu Hospital of Shandong University were included in an independent test cohort to evaluate the model.ResultsAfter feature selection, 32 variables remained. All the five ML algorithms performed well in terms of discriminating between gram-positive and gram-negative bacteremia, but the performance of convolutional neural network (CNN) and random forest (RF) were better than other three algorithms. Consider of the interpretability of models, RF was chosen for further test (ROC-AUC = 0.768; 95%CI = 0.715–0.798, with a sensitivity of 75.20% and a specificity of 63.79%). To expand the application of the model, a decision tree (DT) was built utilizing the major variables, and it achieved an AUC of 0.679 (95%CI = 0.632–0.723), a sensitivity of 66%, and a specificity of 67.82% in the test cohort. When tested in the Qilu Hospital cohort, the ROC-AUC of the RF and DT models were 0.666 (95%CI = 0.579–0.746) and 0.615 (95%CI = 0.526–0.698), respectively. Finally, a software was developed to make the RF- and DT-based prediction models easily accessible.ConclusionThe present ML-based models could effectively discriminate between gram-positive and gram-negative bacteremia based on routine laboratory blood test results. This simple model would be beneficial in terms of guiding timely antibiotic selection and administration in critically ill patients with bacteremia before their pathogen test results are available.

Assessing the Utility of Multiplexed Polymerase Chain Reaction in Detecting Microorganisms Causing Infections in Critically ill Patients

Early sepsis diagnosis is crucial for implementing adequate antibiotic therapy and for patient survival. This study investigated whether using multiplexed PCR for detecting microorganisms in critical septic patients affects initial antibiotic treatment and compared it to microbiological culture. It also explored scenarios where PCR is more effective in clinical practice. One hundred nineteen specimens (83 blood and 36 respiratory specimens) belonging to 93 patients were analyzed. Multiplexed PCR determinations were performed using the FA-BCID Panel (bioMérieux) for blood samples and the FA-Pneumo for respiratory samples. The mean turnaround times were 1.7 h for the FA-BCID and 1.5h for the FA-Pneumo. Conversely, they were 96.1 h for blood cultures and 72.3 h for respiratory cultures. FA-BCID showed a mean sensitivity of 97% and specificity of 100%. FA-Pneumo showed a sensitivity of 100% and specificity of 90%. However, the positive predictive value was only 39%. Discrepancies were common in polymicrobial samples. Based on the PCR results, initial empirical treatment should have been changed in 71% of patients with bloodstream infections and 61% with respiratory infections. We conclude that multiplexed PCR improves the response time in identifying germs with a high degree of coincidence for blood cultures and moderate for respiratory cultures. These results highlight the importance of PCR in choosing an appropriate antibiotic therapy.

Impact of empiric antibiotic therapy on the clinical outcome of acute calculous cholecystitis

PurposeAlthough mortality and morbidity of severe acute calculous cholecystitis (ACC) are still a matter of concern, the impact of inadequate empirical antibiotic therapy has been poorly studied as a risk factor. The objective was to assess the impact of the adequacy of empirical antibiotic therapy on complication and mortality rates in ACC.MethodsThis observational retrospective cohort chart-based single-center study was conducted between 2012 and 2016. A total of 963 consecutive patients were included, and pure ACC was selected. General, clinical, postoperative, and microbiological variables were collected, and risk factors and consequences of inadequate treatment were analyzed.ResultsBile, blood, and/or exudate cultures were obtained in 76.3% of patients, more often in old, male, and severely ill patients (P < 0.001). Patients who were cultured had a higher overall rate of postoperative complications (47.4% vs. 29.7%; P < 0.001), as well as of severe complications (11.6% vs. 4.7%; P = 0.008). Patients with positive cultures had more overall complications (54.8% vs. 39.6%; P = 0.001), more severe complications (16.3% vs. 6.7%; P = 0.001), and higher mortality rates (6% vs. 1.9%; P = 0.012). Patients who received inadequate empirical antibiotic therapy had a fourfold higher mortality rate than those receiving adequate therapy (n = 283; 12.8% vs. 3.4%; P = 0.003). This association was especially marked in severe ACC TG–III patients (n = 132; 18.2 vs. 5.1%; P = 0.018) and remained a predictor of mortality in a binary logistic regression (OR 4.4; 95% CI 1.3–15.3).ConclusionPatients with positive cultures developed more complications and faced higher mortality. Adequate empirical antibiotic therapy appears to be of paramount importance in ACC, particularly in severely ill patients.

Intractable complicated course of tricuspid valve infective endocarditis due to non-compliance of treatment with clinical guidelines with a decisive role of molecular biological study in etiological diagnosis: a case report

A clinical observation of the treatment non-compliance consequences with clinical guidelines and principles of empirical therapy selection in a female patient with intravenous drug abuse, viral hepatitis C and HIV infection, with a history of a COVID-19 and the development of uncontrolled staphylococcal infective endocarditis (IE) of the tricuspid valve, complicated recurrence of early prosthetic IE is presented. Successful treatment was achieved only by a combination of tricuspid valve replacement and the appointment of etiotropic therapy for S. aureus (MSSA). The typical clinical scenario was not accompanied by the choice of adequate empirical antibiotic therapy, despite the high suspicion of association with MSSA, which determined the complicated course of IE. Only the polymerase chain reaction of the heart valve tissue played a key role in the etiological diagnosis. The use of valve tissue polymerase chain reaction in addition to traditional microbiological methods is a valuable diagnostic study.