C-reactive protein velocity discriminates between acute viral and bacterial infections in patients who present with relatively low CRP concentrations

Background To assess the utility of C-reactive protein (CRP) velocity to discriminate between patients with acute viral and bacterial infections who presented with relatively low CRP concentrations and were suspected of having a bacterial infection. Methods We analyzed a retrospective cohort of patients with acute infections who presented to the emergency department (ED) with a relatively low first CRP measurement (CRP1) ≤ 31.9 mg/L and received antibiotics shortly after. We then calculated C-reactive protein velocity (CRPv), milligram per liter per hour, for each patient based on CRP1 and the second CRP value (CRP2) measured within the first 24 h since admission. Finally, we compared CRPv between patients with bacterial and viral infections. Results We have presently analyzed 74 patients with acute bacterial infections and 62 patients with acute viral infections at the mean age of 80 and 66 years respectively, 68 male and 68 female. CRP1 did not differ between both groups of patients (16.2 ± 8.6 and 14.8 ± 8.5 for patients with viral and bacterial infections respectively, p value = 0.336). However, the CRP2 was significantly different between the groups (30.2 ± 21.9 and 75.6 ± 51.3 for patients with viral and bacterial infections respectively, p-value < 0.001) and especially the CRPv was much higher in patients with acute bacterial infections compared to patients with acute viral infections (0.9 ± 1.2 and 4.4 ± 2.7 respectively, p-value < 0.001). Conclusion CRPv and CRP2 are useful biomarkers that can discriminate significantly between patients who present with acute bacterial and viral infections, and relatively low CRP concentration upon admission who were suspected of having a bacterial infection.

Regnase-1 deficiency restrains Klebsiella pneumoniae infection by regulation of a Type I interferon response

Excessive inflammatory responses can cause collateral tissue damage or autoimmune inflammation, sometimes with severe morbidity or mortality. During host defense responses, numerous negative feedback mechanisms are established to prevent excessive unchecked inflammation. However, this restraint can sometimes come at the cost of suboptimal infection control, and we do not fully understand how this balance is maintained during different infection settings. The endoribonuclease Regnase-1 (Reg1, Zc3h12a, MCPIP1) is an RNA binding protein (RBP) that binds and degrades many target mRNA transcripts. Reg1 is a potent feedback regulator of IL-17 and LPS signal transduction, among other stimuli. Consequently, Reg1 deficiency exacerbates autoimmune inflammation in multiple mouse models, but on the other hand, reduced Reg1 improves immunity to fungal infection. To date, the role of Reg1 in bacterial immunity is poorly defined. Here, we show that mice deficient in Reg1 are more resistant to pulmonary Klebsiella pneumoniae (KP) infection. Unexpectedly, effects of Reg1 deficiency were not due to accelerated eradication of bacteria or increased pro-inflammatory cytokine expression. Rather, alveolar macrophages from Reg1-deficient mice showed enrichment of Type I IFN-related genes upon KP infection, accompanied by increased Ifnb1 expression. Surprisingly, the stability of Ifnb1 mRNA was not altered by Reg1-deficiency; rather, mRNA encoding its upstream regulator IRF7 appeared to be a more prominent target. Thus, impaired Reg1 induces Type I IFN and enhances resistance to KP, raising the possibility that Reg1 could be a potential clinical target in acute bacterial infections.

Diagnosis of Streptococcus pneumoniae infection using circulating antibody secreting cells

Background Streptococcus pneumoniae infections cause morbidity and mortality worldwide. A rapid, simple diagnostic method could reduce the time needed to introduce definitive therapy potentially improving patient outcomes. Methods We introduce two new methods for diagnosing S. pneumoniae infections by measuring the presence of newly activated, pathogen-specific, circulating Antibody Secreting Cells (ASC). First, ASC were detected by ELISpot assays that measure cells secreting antibodies specific for signature antigens. Second, the antibodies secreted by isolated ASC were collected in vitro in a novel matrix, MENSA (media enriched with newly synthesized antibodies) and antibodies against S. pneumoniae antigens were measured using Luminex immunoassays. Each assay was evaluated using blood from S. pneumoniae and non-S. pneumoniae-infected adult patients. Results We enrolled 23 patients with culture-confirmed S. pneumoniae infections and 24 controls consisting of 12 non-S. pneumoniae infections, 10 healthy donors and two colonized with S. pneumoniae. By ELISpot assays, twenty-one of 23 infected patients were positive, and all 24 controls were negative. Using MENSA samples, four of five S. pneumoniae-infected patients were positive by Luminex immunoassays while all five non-S. pneumoniae-infected patients were negative. Conclusion Specific antibodies produced by activated ASC may provide a simple diagnostic for ongoing S. pneumoniae infections. This method has the potential to diagnose acute bacterial infections.

The safety of ceftolozane-tazobactam for the treatment of acute bacterial infections: a systemic review and meta-analysis

Objective(s): The aim of this study was to conduct a meta-analysis to assess the clinical safety of ceftolozane-tazobactam for the treatment of acute bacterial infections in adult patients. Methods: The PubMed, Embase, and Cochrane databases were searched from their inception until May 2020 for relevant randomized controlled trials (RCTs). Only RCTs evaluating the risk of adverse events (AEs) for ceftolozane-tazobactam and comparative treatments for acute bacterial infections in adult patients were included. Results: Overall, four RCTs including a total of 2924 patients (1475 in the ceftolozane-tazobactam group and 1449 in the control group) were included in the meta-analysis. The rate of treatment-emergent AEs was 51.3% (748/1458) in the ceftolozane-tazobactam group, which was comparable to the control group, 49.9% [714/1430; odd’s ratio (OR), 1.06; 95% confidence interval (CI), 0.91–1.25; I2 = 0%]. In addition, no difference was observed between the ceftolozane-tazobactam and control groups in terms of the risk of serious AEs (OR, 1.22; 95% CI, 0.93–1.61; I2 = 15.5%) and the risk of discontinuing the study drug due to AEs (OR, 0.85; 95% CI, 0.55–1.33; I2 = 0%). The rate of all-cause mortality did not significantly differ between the ceftolozane-tazobactam and control groups (OR, 1.11; 95% CI, 0.82–1.50; I2 = 0%). The only exception was the risk of Clostridiodes difficile ( C. difficile) colitis, where ceftolozane-tazobactam treatment was associated with a significantly higher risk compared with the control group [0.72% (10/1376) versus 0.14% (2/1391), OR, 3.84; 95% CI, 1.23–11.97; I2 = 0%]. Conclusion: Ceftolozane-tazobactam treatment is as tolerable as comparative treatment options for acute bacterial infections in adult patients, however it has an increased risk of C. difficile infection. As a novel broad-spectrum antibiotic, ceftolozane-tazobactam could be a safe therapeutic option for use in common clinical practice. Plain language summary The safety of ceftolozane-tazobactam (an antibiotics) for the treatment of acute bacterial infections Objective(s): Ceftolozane-tazobactam is an effective antibiotic for the treatment of acute bacterial infections. This study conducts a meta-analysis to assess the clinical safety (side effects) of ceftolozane-tazobactam for the treatment of acute bacterial infections in adult patients compared with other drugs. Methods: We extracted data from four randomized controlled trials, including a total of 2924 patients (1475 in the ceftolozane-tazobactam group and 1449 in the control group). Results: The rate of treatment related adverse events (AEs) was similar in the ceftolozane-tazobactam group (51.3%) and control group (49.9%). There was also no difference in risk of serious adverse events, the risk of discontinuing the study drug due to AEs, and all-cause mortality. The only exception was the risk of Clostridiodes difficile colitis (a cause of antibiotic-associated diarrhea), where ceftolozane-tazobactam treatment was associated with a significantly higher risk compared with the control group. Conclusion: In conclusion, as a novel broad-spectrum antibiotic, ceftolozane-tazobactam could be a safe therapeutic option for use in clinical practice.

Development of Peptides that Inhibit Aminoglycoside-Modifying Enzymes and β-Lactamases for Control of Resistant Bacteria

: Aminoglycosides and β-lactams are the most commonly used antimicrobial agents in clinical practice. This occurs because they are capable of acting in the treatment of acute bacterial infections. However, the effectiveness of antibiotics has been constantly threatened due to bacterial pathogens producing resistance enzymes. Among them, the aminoglycoside-modifying enzymes (AMEs) and β-lactamase enzymes are the most frequently reported resistance mechanisms. AMEs can inactivate aminoglycosides by adding specific chemical molecules in the compound, whereas β-lactamases hydrolyze the β-lactams ring, preventing drug-target interaction. Thus, these enzymes provide a scenario of multidrug-resistance and a significant threat to public health at a global level. In response to this challenge, in recent decades, several studies have focused on the development of inhibitors that can restore aminoglycosides and β-lactams activity. In this context, peptides appear as a promising approach in the field of inhibitors for future antibacterial therapies, as multiresistant bacteria may be susceptible to these molecules. Therefore, this review focused on the most recent findings related to peptide-based inhibitors that act on AMEs and β-lactamases, and how these molecules could be used for future treatment strategies.

EVALUATING THE ETIOLOGY AND DISEASE SPECIFIC CLINICAL PROFILES OF ACUTE UNDIFFERENTIATED FEBRILE ILLNESS

Background: To evaluate the etiology and disease specific clinical profiles of acute undifferentiated febrile illness (AUFI) in Medicine Department of Govt. Medical College and Hospital, Bettiah, W. Champaran, Bihar. Methods: This 1 year prospective, observational study was conducted in Govt. Medical College and Hospital, Bettiah, Bihar from October 2019 to September 2020 in 150 patients. Clinical evaluation and relevant investigations like Blood culture; malarial parasites and febrile serology (acute and convalescent) were performed. Results and Observation: A total of 150 AUFI patients were evaluated: scrub typhus (19); malaria (3); enteric fever (2); dengue (11); leptospirosis (19); hantavirus (1), acute bacterial infections (14), HIV (1), hepatitis (1), and unclear diagnoses (79). Conclusion: This study reports discovery of dengue, typhus fever, leptospirosis, and rare disease like Hanta and more number undiagnosed cases ranging from 15% to 42% in local community. This shows that further research is required in identifying the etiology of undifferentiated fevers.