Early Antibiotic Treatment Research Articles

Procalcitonin-guided antibiotic treatment in patients with cancer: a patient-level meta-analysis from randomized controlled trials

BackgroundUse of serum procalcitonin (PCT), an inflammatory biomarker for bacterial infections, has shown promising results for early stopping antibiotic treatment among patients with respiratory infections and sepsis. There is need for additional data regarding effectiveness and safety of this concept among patients with cancer.MethodsIndividual data of patients with a documented diagnosis of cancer and proven or suspected respiratory infection and/or sepsis were extracted from previous trials where adult patients were randomized to receive antibiotic treatment based on a PCT protocol or usual care (control group). The primary efficacy and safety endpoints were antibiotic exposure and 28-day all-cause mortality.ResultsThis individual-patient data meta-analysis included 777 patients with a diagnosis of cancer from 15 randomized-controlled trials. Regarding efficacy, there was a 18% reduction in antibiotic exposure in patients randomized to PCT-guided care compared to usual care ([days] 8.2 ± 6.6 vs. 9.8 ± 7.3; adjusted difference, − 1.77 [95% CI, − 2.74 to − 0.80]; p < 0.001). Regarding safety, there were 72 deaths in 379 patients in the PCT-guided group (19.0%) compared to 91 deaths in 398 participants in the usual care group (22.9%) resulting in an adjusted OR of 0.78 (95% CI, 0.60 to 1.02). A subgroup analysis showed a significant reduction in mortality in patients younger than 70 years (adjusted OR, 0.58 [95% CI, 0.40 to 0.86]).ConclusionResult of this individual patient meta-analysis from 15 previous trials suggests that among patients with cancer and suspected or proven respiratory infection or sepsis, use of PCT to guide antibiotic treatment decisions results in reduced antibiotic exposure with a possible reduction in mortality, particularly among younger patients.

γδ T Cells Mediate Protection against Neutrophil-associated Lung Inflammation in Pulmonary Melioidosis.

Pulmonary melioidosis is a severe tropical infection caused by Burkholderia pseudomallei and is associated with high mortality, despite early antibiotic treatment. γδ T cells have been increasingly implicated as drivers of the host neutrophil response during bacterial pneumonia, but their role in pulmonary melioidosis is unknown. Here, we report that in patients with melioidosis, a lower peripheral blood γδ T-cell concentration is associated with higher mortality, even when adjusting for severity of illness. γδ T cells were also enriched in the lung and protected against mortality in a mouse model of pulmonary melioidosis. γδ T-cell deficiency in infected mice induced an early recruitment of neutrophils to the lung, independent of bacterial burden. Subsequently, γδ T-cell deficiency resulted in increased neutrophil-associated inflammation in the lung as well as impaired bacterial clearance. In addition, γδ T cells influenced neutrophil function and subset diversity in the lung after infection. Our results indicate that γδ T cells serve a novel protective role in the lung during severe bacterial pneumonia by regulating excessive neutrophil-associated inflammation.

Infection and Inflammation in the Cystic fibrosis (CF) airway.

Cystic fibrosis (CF) airway disease is characterized by chronic infection and neutrophil-driven inflammation, leading to progressive airway damage and early mortality. Infection with Pseudomonas aeruginosa significantly impacts morbidity and mortality, requiring early detection and aggressive antibiotic treatment. Controlling inflammation remains difficult due to the limited availability of effective anti-inflammatory treatments. CFTR modulators show potential in reducing inflammation, but further research is needed. Effective management of CF lung disease requires a comprehensive approach addressing both infection and inflammation.

Clinical Application of Metagenomic Next-Generation Sequencing in Sepsis Patients with Early Antibiotic Treatment.

This study aimed to evaluate the clinical utility of metagenomic next-generation sequencing (mNGS) in sepsis patients who received early empirical antibiotic treatment. A retrospective analysis was conducted on clinical data from sepsis patients diagnosed in the Emergency Intensive Care Unit (EICU) between April 2019 and May 2023. All patients underwent standard conventional microbiological testing. Patients were categorized into either the mNGS group or the control group based on whether they underwent mNGS tests. Baseline variables were matched using propensity scores. Out of 461 sepsis patients screened, 130 were included after propensity matching, with 65 patients in each group. Despite prior antibiotic treatment, 57 cases (87.69%) in the mNGS group had positive mNGS results, exceeding the culture detection rate (52.31%). Besides, a higher proportion of patients in the mNGS group experienced antibiotic adjustments compared to the control group (72.31% vs 53.85%). Mortality rates were also compared based on the duration of antibiotic exposure before mNGS sampling. Patients exposed to antibiotics for less than 24hours had a lower mortality rate compared to those exposed for over 8 days (22.22% vs 42.86%). COX multivariate analysis identified mNGS testing, underlying diseases, lymphocyte percentage, infection site (respiratory and bloodstream) as independent risk factors for mortality in sepsis patients. With increased antibiotic exposure time, the positive rate of culture testing significantly decreased (44.44% vs 59.52% vs 35.71%, P = 0.031), whereas the positive rate of mNGS remained stable (77.78% vs 88.10% vs 92.86%, P = 0.557). mNGS demonstrated less susceptibility to antibiotic exposure. Early mNGS detection positively impacted the prognosis of sepsis patients.

UNFORESEEN BARRIER IN GOUT TREATMENT: A CASE OF COEXISTING LYME DISEASE

Refractory gout and Lyme disease are distinct conditions that, when coexisting, pose significant diagnostic and therapeutic challenges, particularly in regions endemic for Lyme disease. This case report presents a 49-year-old male with a three-year history of gout, presenting with acute arthritis of the first metatarsophalangeal joint, unresponsive to standard urate-lowering therapy. Despite treatment with colchicine and prednisone, the patient’s symptoms persisted, and inflammatory markers remained elevated. Imaging revealed findings consistent with gouty arthritis, but due to the atypical treatment response, further testing was conducted. Serological analysis confirmed infection with Borrelia burgdorferi, establishing the diagnosis of concurrent Lyme disease. The addition of doxycycline to the treatment regimen resulted in significant clinical improvement within days. This case highlights the importance of considering Lyme disease in patients with refractory gout in areas endemic for Lyme disease. While rare cases of Lyme disease mimicking gout have been reported, this is among the first documented instances of their coexistence. Early recognition and appropriate antibiotic treatment are critical in preventing complications and ensuring optimal management of both conditions.

Clinical Outcome of Surgical Treatment of Giant Femoral Artery Pseudoaneurysms

Femoral artery was used as an access site for cardiovascular procedures and by IV drug abusers, Femoral Artery Pseudoaneurysm (FAP) was a common complication associated with these procedures. Objective: To evaluate clinical outcome of surgical repair of femoral artery pseudoaneurysms. Methods: The prospective study was conducted in Doctors Hospital, Lahore from October 2022 to October 2023. The study included patients with giant femoral artery pseudoaneurysms who required surgical intervention. Data from a total of 50 patients were included in whom both peripheral vascular interventions and percutaneous cardiac catheterization was performed. Patients were followed up at 1-, 3-, 6- and 12 months postoperatively. SPSS version 23.0 was used for data analysis. Results: All patients underwent open surgical treatment. Of 50 patients, 25 (50%) had SFA pseudoaneurysm, 20 (40%) had CFA pseudoaneurysm and 5 (10%) had PFA pseudoaneurysm. The mean duration of clinical manifestations was 16.30 ± 7.74 days. Surgical repair was successful in all 50 (100%) patients and distal ischemia was fully resolved. There was no case of limb loss or post-operative mortality. One patient had an infection in the groin wound and had raised Total leucocyte count (TLC), which was resolved by early drainage and antibiotic treatment. Patients were followed up at 1, 3, 6, and 12 months and there were no signs of clinical or angiographic evidence of post-operative complications and changes in distal pulse. Conclusion: Surgical repair was first-line treatment for giant FAP. It was clinically feasible and has a high success rate and low complication rate.

Experimental immunotherapy of association infections of the gastrointestinal tract of newborn calves using yolk melange enriched with specific Y class immunoglobulins

Mass gastrointestinal diseases of newborn calves manifested by symptoms of diarrhea are caused by various etiological factors and most often occur in the form of mixed infections. Mixed infections have a more severe diarrhea than mono-infections. The economic consequences of such infections due to the high prevalence, frequent mortality and loss of productivity during further exploitation of the animal can be significant. The most common causative agents of gastrointestinal diseases of newborn calves of viral etiology is rotavirus and coronavirus infections. Mixed (viral-bacterial) infection can lead to 100% mortality of the diseased calves. Specific vaccination of springer cows against gastrointestinal pathogens in calves, which is performed to increase the number of pathogen-specific immunoglobulins in the colostrum at calf birth, and ingestion of colostrum by the calves during the first 4 hours of life are the most important strategies to prevent severe diarrhea. But as practice shows, this is not always enough. The purpose of this work was to study the effectiveness of immunoprophylaxis of associative infections of the gastrointestinal tract of newborn calves with the use of melange prepared from chicken eggs previously immunized with the vaccine "Rotagal" (Pharmagal-BIO s.r.o., Slovakia), used for the prevention of colibacillosis, rotavirus and coronavirus infections of cattle. As a result of the study, it was established that the addition of yolk melange rich in specific immunoglobulins of Y class to the colostrum in the first hours of life of the calves has a pronounced prophylactic effect, facilitates the course of the infectious process in case of the disease, saves costs for the treatment of sick animals, increases survival rate, contributes to the acceleration of live weight gain. The use of an immunobiological preparation based on transovarial immunoglobulins has a positive effect on the indicators of nonspecific resistance of newborn calves compared to the calves with early postnatal disease and antibiotic treatment.

Interplay between Multisystem Inflammatory Syndrome in Children, Interleukin 6, Microbiome, and Gut Barrier Integrity

A severe consequence of SARS-CoV-2 infection that manifests as systemic inflammation and multi-organ involvement is called Multisystem Inflammatory Syndrome in Children (MIS-C). This review examines the possible relationship between gut barrier integrity, the microbiome, dysregulation of interleukin 6 (IL-6) signaling, and MIS-C. Clinical and biochemical features of MIS-C are comparable to those of other hyper-inflammatory syndromes, suggesting a dysregulated immune response. One possible explanation for the systemic inflammation seen in MIS-C patients is the SARS-CoV-2-induced dysregulation of the IL-6 signaling pathway. In addition, new data suggest a reciprocal link between gut barrier integrity and IL-6. SARS-CoV-2 exhibits bacteriophage-like behavior, highlighting the role of bacteria as a reservoir for the virus and emphasizing the importance of understanding the bacteriophagic mechanism of the virus in fecal–oral transmission. The increased translocation of viral products and bacterial toxins may result from disrupting the intestinal barrier and cause systemic inflammation. On the other hand, systemic inflammation can weaken the integrity of the intestinal barrier, which feeds back into the loop of immunological dysregulation. In the context of MIS-C, understanding the interaction between SARS-CoV-2 infection, IL-6, and gut barrier integrity may shed light on the etiology of the disease and guide treatment options. Since children with gut dysbiosis may be more susceptible to MIS-C, it is critical to reinforce their microbiome through probiotics supplementation, and plant-fiber-rich diets (prebiotics). Early antibiotic treatment and the use of zonulin antagonists should also be considered.

Utility of shaking chills as a diagnostic sign for bacteremia in adults: a systematic review and meta-analysis

BackgroundAccurate prediction of bacteremia is essential for guiding blood culture collection and optimal antibiotic treatment. Shaking chills, defined as a subjective chill sensation with objective body shivering, have been suggested as a potential predictor of bacteremia; however, conflicting findings exist. To address the evidence gap, we conducted a systematic review and meta-analysis of studies to assess the diagnostic accuracy of shaking chills for predicting bacteremia among adult patients.MethodsWe included studies reporting the diagnostic accuracy of shaking chills or chills for bacteremia. Adult patients with suspected bacteremia who underwent at least one set of blood cultures were included. Our main analysis focused on studies that assessed shaking chills. We searched these studies through CENTRAL, MEDLINE, Embase, the World Health Organization ICTRP Search Portal, and ClinicalTrials.gov. Study selection, data extraction, evaluation for risk of bias, and applicability using the QUADAS-2 tool were conducted by two independent investigators. We estimated a summary receiver operating characteristic curve and a summary point of sensitivity and specificity of the index tests, using a hierarchical model and the bivariate model, respectively.ResultsWe identified 19 studies with a total of 14,641 patients in which the accuracy of shaking chills was evaluated. The pooled sensitivity and specificity of shaking chills were 0.37 (95% confidence interval [CI], 0.29 to 0.45) and 0.87 (95% CI, 0.83 to 0.90), respectively. Most studies had a low risk of bias in the index test domain and a high risk of bias and a high applicability concern in the patient-selection domain.ConclusionsShaking chills are a highly specific but less sensitive predictor of bacteremia. Blood cultures and early initiation of antibiotics should be considered for patients with an episode of shaking chills; however, the absence of shaking chills must not lead to exclusion of bacteremia and early antibiotic treatment.

The use of antibiotics in the early stage of acute exacerbation of chronic obstructive pulmonary disease in patients without obvious signs of infection: a multicenter, randomized, parallel-controlled study.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence and mortality. In some acute exacerbations of COPD (AECOPD) in patients with no obvious signs of infection, early antibiotic treatment seems to clinically improve the disease, but more studies are needed to determine the prognostic impact of antibiotic treatment in AECOPD patients with no obvious signs of infection. To clarify the impact of antibiotic treatment on the short-term and long-term prognoses of AECOPD patients without obvious signs of infection. The impact of the two treatment methods on the prognosis of patients was compared at 30, 90, 180, and 360days after discharge. A multicenter, randomized, parallel-controlled clinical trial was conducted in a department of respiratory and critical care medicine in Central China. All patients met the inclusion criteria for AECOPD, and the patients were randomly assigned to the antibiotic group or the nonantibiotic group at a 1:1 ratio. Patients in the antibiotic group were given moxifloxacin 400mg/day intravenously for 7days. Patients in the nonantibiotic group were intravenously injected with the same amount of normal saline as the amount of moxifloxacin given to those in the antibiotic group for 7days. There were 406 patients in the antibiotic group and 410 patients in the nonantibiotic group. During the short-term and long-term follow-ups, the acute exacerbation frequency, intensive care unit (ICU) treatment rate, mortality, and mMRC and CAT scores were not significantly different between the two groups (p > 0.05). At the 180- and 360-day follow-ups, the forced expiratory volume in 1s (FEV1%) and peak expiratory flow (PEF) were not significantly different between the two groups (p > 0.05). The 30-day readmission rate was significantly lower in the antibiotic group than in the nonantibiotic group (p < 0.05). The time from discharge to the first acute exacerbation was not significantly different between the two groups (p > 0.05). The length of the first hospital stay after discharge was significantly lower in the antibiotic group (5.84days) than in the nonantibiotic group (6.75days) (p < 0.05). At the 30-day follow-up, the acute exacerbation frequency, age, C-reactive protein (CRP) level, and sputum viscosity were significantly greater in the nonantibiotic group than in the antibiotic group (p < 0.05). In addition, according to the receiver operating characteristic (ROC) analysis, the frequency of acute exacerbations at the 30-day follow-up was significantly greater in COPD patients aged >62.5years, with a CRP level >12.56mg/L or with a sputum viscosity >III, in the nonantibiotic group than in those in the antibiotic group, suggesting that the short-term prognosis was poor. Patients who are >62.5years of age, have a CRP concentration >12.56mg/L, or have a sputum viscosity >III without obvious signs of infection should be treated with antibiotics to improve their short-term prognosis. (https://www.chictr.org.cn), (ChiCTR1800018921).

Diagnostic accuracy of pancreatic stone protein in patients with sepsis: a systematic review and meta-analysis

BackgroundSepsis is a common syndrome of multiorgan system dysfunction secondary to the dysregulated inflammatory response to infection. The role of pancreatic stone protein (PSP) in diagnosing sepsis has been investigated in previous studies. The meta-analysis aimed to comprehensively investigate the diagnostic value of PSP in identifying sepsis.MethodsPubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI), were systematically searched. Studies investigating the diagnostic performance of PSP were included. Pooled sensitivity, specificity, positive Likelihood Ratio (+ LR) and negative Likelihood Ratio (-LR), diagnostic odds ratio (DOR), and area under the curve (AUC) of summary receiver operating characteristic (SROC) were calculated.ResultsThe sensitivity of PSP was 0.88 (95% CI: 0.77–0.94), and the pooled specificity was 0.78 (95% CI: 0.65–0.87). Pooled + LR, -LR, and DOR were 4.1 (2.3, 7.3), 0.16 (0.07, 0.34), and 26 (7, 98). The AUC value for the SROC of PSP was 0.90 (0.87, 0.92). The pooled sensitivity, specificity, + LR and - LR, and DOR for PSP among neonates were 0.91 (95% CI: 0.84, 0.96), 0.66 (95% CI: 0.58, 0.74), 3.97 (95% CI: 0.53, 29.58), 0.13 (95% CI: 0.02, 1.00), and 31.27 (95% CI: 0.97, 1004.60).ConclusionsThis study indicates that PSP demonstrated favorable diagnostic accuracy in detecting sepsis. Well-designed studies are warranted to ascertain the value of PSP measurement to guide early empirical antibiotic treatment, particularly in neonates.

PCR-positive meningococcal CSF infection without pleocytosis but high IL-6 and IL-8

BackgroundMeningococcal meningitis is still a severe disease causing high mortality and morbidity rates. Early diagnosis is crucial to ensure prompt antibiotic therapy. However, identification of the pathogen can be challenging.Case presentationA 32-year-old male patient with systemic lupus erythematosus (SLE) presented to the emergency room with fever, nausea, vomiting, headache and lower back pain as well as multiple petechial bleedings. On suspicion of meningococcal infection, the emergency doctor had already administered one dose of ceftriaxone before arrival to the clinic. Blood works showed massive inflammation due to bacterial infection. Cerebrospinal fluid (CSF) analysis showed normal cell count, protein and glucose levels but PCR was positive for Neisseria meningitis and IL-6 as well as IL-8 were elevated. On antibiotic therapy with ceftriaxone, the patient’s condition improved quickly.ConclusionsWe present a rare case of meningococcal infection of the CSF in a SLE patient without further CSF abnormalities. We discuss the involvement of early antibiotic treatment and the role of the patient’s immune status in the normal CSF findings of this case. Moreover, this case demonstrates the importance of early antibiotic therapy in bacterial meningitis for the clinical outcome.

Identification of pathogen composition in a Chinese population with iatrogenic and native vertebral osteomyelitis by using mNGS

Background Early antimicrobial therapy is crucial regarding the prognosis of vertebral osteomyelitis, but early pathogen diagnosis remains challenging. Objective In this study, we aimed to differentiate the types of pathogens in iatrogenic vertebral osteomyelitis (IVO) and native vertebral osteomyelitis (NVO) to guide early antibiotic treatment. Methods A total of 145 patients, who had confirmed spinal infection and underwent metagenomic next-generation sequencing (mNGS) testing, were included, with 114 in the NVO group and 31 in the IVO group. Using mNGS, we detected and classified 53 pathogens in the 31 patients in the IVO group and 169 pathogens in the 114 patients in the NVO group. To further distinguish IVO from NVO, we employed machine learning algorithms to select serum biomarkers and developed a nomogram model. Results The results revealed that the proportion of the Actinobacteria phylum in the NVO group was approximately 28.40%, which was significantly higher than the 15.09% in the IVO group. Conversely, the proportion of the Firmicutes phylum (39.62%) in the IVO group was markedly increased compared to the 21.30% in the NVO group. Further genus-level classification demonstrated that Staphylococcus was the most common pathogen in the IVO group, whereas Mycobacterium was predominant in the NVO group. Through LASSO regression and random forest algorithms, we identified 5 serum biomarkers including percentage of basophils (BASO%), percentage of monocytes (Mono%), platelet volume (PCT), globulin (G), activated partial thromboplastin time (APTT) for distinguishing IVO from NVO. Based on these biomarkers, we established a nomogram model capable of accurately discriminating between the two conditions. Conclusion The results of this study hold promise in providing valuable guidance to clinical practitioners for the differential diagnosis and early antimicrobial treatment of vertebral osteomyelitis.

Acute Kidney Injury Associated with Severe Leptospirosis: Fatal Re-Emerging Disease in Latin America

Leptospirosis is a re-emerging zoonotic disease that has had an unprecedented impact on most health systems in the world. The spectrum of symptoms is variable and usually ranges from asymptomatic cases to severe manifestations involving multiple organ dysfunction accompanied by jaundice, hemorrhage, meningitis, and acute kidney injury that requires the need for intensive care assistance. Although early antibiotic treatment is usually effective, in severe cases, it may require renal replacement therapy, invasive mechanical ventilation, vasoactive support, and invasive hemodynamic monitoring, increasing the risk of death. In Latin America, the real burden of acute kidney injury in this condition is unknown and may be underestimated due to the rapid progression of the disease, similar to other vector zoonoses, and the low coverage of diagnostic tests in primary care, especially in rural regions. Therefore, below, we review the clinical aspects and describe the scientific, clinical, and therapeutic evidence of acute kidney injury attributed to Leptospira spp. and its relevance in patients with severe leptospirosis in Latin America.

Clinical characteristics of 11 patients with Vibrio vulnificus infection and the establishment of a rapid diagnosis procedure for this disease

Clinical characteristics of 11 patients with Vibrio vulnificus infection and the establishment of a rapid diagnosis procedure for this disease

A retrospective cohort study on early antibiotic use in vaccinated and unvaccinated COVID-19 patients.

The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral replication in the gut microbiome, and control toxicological production from the human microbiome. To study the impact of specific antibiotics on recovery from COVID-19 and long COVID (LC) taking into account: vaccination status, comorbidities, SARS-CoV-2 wave, time of initiation of antibiotic therapy and concomitant use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). A total of 211 COVID-19 patients were included in the study: of which 59 were vaccinated with mRNA vaccines against SARS-CoV-2 while 152 were unvaccinated. Patients were enrolled in three waves: from September 2020 to October 2022, corresponding to the emergence of the pre-Delta, Delta, and Omicron variants of the SARS-CoV-2 virus. The three criteria for enrolling patients were: oropharyngeal swab positivity or fecal findings; moderate symptoms with antibiotic intake; and measurement of blood oxygen saturation during the period of illness. The use of antibiotic combinations, such as amoxicillin with clavulanic acid (875 + 125 mg tablets, every 12 h) plus rifaximin (400 mg tablets every 12 h), as first choice, as suggested from the previous data, or azithromycin (500 mg tablets every 24 h), plus rifaximin as above, allows healthcare professionals to focus on the gut microbiome and its implications in COVID-19 disease during patient care. The primary outcome measured in this study was the estimated average treatment effect, which quantified the difference in mean recovery between patients receiving antibiotics and those not receiving antibiotics at 3 and 9 days after the start of treatment. In the analysis, both vaccinated and unvaccinated groups had a median illness duration of 7 days (interquartile range [IQR] 6-9 days for each; recovery crude hazard ratio [HR] = 0.94, p = 0.700). The median illness duration for the pre-Delta and Delta waves was 8 days (IQR 7-10 days), while it was shorter, 6.5 days, for Omicron (IQR 6-8 days; recovery crude HR = 1.71, p < 0.001). These results were confirmed by multivariate analysis. Patients with comorbidities had a significantly longer disease duration: median 8 days (IQR 7-10 days) compared to 7 days (IQR 6-8 days) for those without comorbidities (crude HR = 0.75, p = 0.038), but this result was not confirmed in multivariate analysis as statistical significance was lost. Early initiation of antibiotic therapy resulted in a significantly shorter recovery time (crude HR = 4.74, p < 0.001). Concomitant use of NSAIDs did not reduce disease duration and in multivariate analysis prolonged the disease (p = 0.041). A subgroup of 42 patients receiving corticosteroids for a median of 3 days (IQR 3-6 days) had a longer recovery time (median 9 days, IQR 8-10 days) compared to others (median 7 days, IQR 6-8 days; crude HR = 0.542, p < 0.001), as confirmed also by the adjusted HR. In this study, a statistically significant reduction in recovery time was observed among patients who received early antibiotic treatment. Early initiation of antibiotics played a crucial role in maintaining higher levels of blood oxygen saturation. In addition, it is worth noting that a significant number of patients who received antibiotics in the first 3 days and for a duration of 7 days, during the acute phase did not develop LC.

(131) Predictors of Success with Early Antibiotic Therapy for Penile Implant Infection: Patients from a Prospective Randomized Study Comparing DNA Sequencing versus Traditional Cultures

Abstract Introduction Traditional culture is the current standard-of-care to determine therapeutic antibiotics for patients suffering from penile prosthesis (PP) infections. However, approximately 30% to 50% of PPs removed for infection are culture negative. Next-generation sequencing (NGS) of DNA has proven to be beneficial in its thorough analysis of biofilm composition. However, there are no existing clinical measures for identifying presenting characteristics of patients of successful or failed antibiotic treatments. Objective The purpose of this early dataset is to identify patient characteristics predicting success or failure with early antibiotic therapy in the setting of penile implant infection. Methods Upon institutional review board approval, adult men undergoing treatment for mild to moderate clinical (non-systemic) PP infection are enrolled after providing informed consent. Enrollees are randomized into one of two analytic arms – traditional culture or NGS. Traditional culture and NGS samples are collected upon clinical presentation prior to initiation of antibiotics. Patients are started on set empiric antibiotics and randomized to traditional culture or NGS. Patients follow up within ten days of antibiotic initiation and at six months complete a safety and compliance questionnaire which assesses symptoms, device function, and patient satisfaction. Results Of the 8 patients enrolled in the study, 4 eventually underwent device explantation due to worsening infection within 7 days of initiating empiric antibiotic treatment. The other 4 patients went on to the next step in the protocol. In evaluating these 2 groups: if there was penile shaft tenderness (2/4) this required PP removal prior to 7 days; while if there was no penile tenderness, the patient ended up with the device surviving at least 10 days. Patients on the NGS arm included those that survived the entire 6-month period. Currently, there are 11 active sites already participating; more patients and more centers are being enrolled in the study. Conclusions Penile shaft tenderness was a more common presentation in patients who failed early antibiotic treatment for penile implant infection. Recruitment of additional patients to this prospective, randomized controlled trial will help to identify additional favorable presentations of penile implant infection in addition to comparing the utility and outcomes of NGS and culture. Disclosure Yes, this is sponsored by industry/sponsor: Microgen Dx. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Microgen Dx.

Good Performance of Revised Scoring Systems in Predicting Clinical Outcomes of Aeromonas Bacteremia in the Emergency Department: A Retrospective Observational Study.

Aeromonas species, Gram-negative, non-sporulating, facultative, and anaerobic bacilli, widely distributed in aquatic environments, derive various infections, including bacteremia. Most of these infections were opportunistic and found in patients with predisposing conditions. Among the infections, bacteremia remains with notable mortality, reported from 15% to 45%. However, predicting systems for assessing the mortality risk of this disease have yet to be investigated. We aimed to validate the performance of specific predictive scoring systems to assess the clinical outcomes of Aeromonas bacteremia and applied the revised systems to predict mortality risk. A retrospective observational study reviewed patients with bacteremia caused by Aeromonas spp. based on at least one positive blood culture sample collected in the emergency department from January 2012 to December 2020. The outcome was in-hospital mortality. We used seven predictive scoring systems to predict the clinical outcome. According to the effectiveness in predicting mortality, we revised three of the seven predictive scoring systems by specific characteristics to refine their risk-predicting performances. We enrolled 165 patients with bacteremia caused by Aeromonas spp., including 121 males (73.3%) and 44 females (26.7%), with a mean age of 66.1 ± 14.9 years and an average length of hospital stay of 12.4 ± 10.9 days. The overall mortality rate was 32.7% (54/165). The non-survivors had significantly higher scores in MEDS (6.7 ± 4.2 vs. 12.2 ± 3.3, p < 0.001), NEWS (4.0 ± 2.8 vs. 5.3 ± 3.0, p = 0.008), and qSOFA (0.3 ± 0.6 vs. 0.6 ± 0.7, p = 0.007). Regarding mortality risk prediction, the MEDS demonstrated the best predictive power with AUC of ROC measured up to 0.834, followed by NEWS (0.626) and qSOFA (0.608). We revised the MEDS, NEWS, and qSOFA by hemoglobin and lactate. We found that the revised scores had better powerful performance, including 0.859, 0.767, and 0.691 of the AUC of ROC, if the revised MEDS ≥10, revised NEWS ≥8, and revised qSOFA ≥2, respectively. MEDS, NEWS, and qSOFA were good tools for predicting outcomes in patients with Aeromonas spp. bacteremia. The revised MEDS, NEWS, and qSOFA demonstrated more powerful predicting performance than the original scoring systems. We suggested that patients with higher scores in revised MEDS (≥10), revised NEWS (≥8), and revised qSOFA (≥2) received early goal-directed therapy and appropriate broad-spectrum antibiotic treatment as early as possible to reduce mortality.

The Impact of Early Antibiotic Use on Clinical Outcomes of Patients Hospitalized with COVID-19: A Propensity Score-Matched Analysis.

Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown. In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness. We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246-4.060), p = 1.000) and ICU admission (HR=0.436(0.093-2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296-1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221-8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort. Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.

Early empiric antibiotic use in COVID-19 patients: results from the international VIRUS registry

ObjectivesCOVID-19 escalated inappropriate antibiotic use. We determined the distribution of pathogens causing community-acquired co-infections, the rate, and factors associated with early empiric antibiotic (EEAB) treatment among hospitalized COVID-19 patients. MethodsThe Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry including 68,428 patients from 28 countries enrolled between January 2020 and October 2021 were screened. After exclusions, 7830 patients were included in the analysis. Azithromycin and/or other antibiotic treatment given within the first 3 days of hospitalization was investigated. Univariate and multivariate analyses were performed to determine factors associated with EEAB use. ResultsThe majority (6214, 79.4%) of patients received EEAB, with azithromycin combination being the most frequent (3146, 40.2%). As the pandemic advanced, the proportion of patients receiving EEAB regressed from 84.4% (786/931) in January-March 2020 to 65.2% (30/46) in April-June 2021 (P < 0.001). Beta-lactams, especially ceftriaxone was the most commonly used antibiotic. Staphylococcus aureus was the most commonly isolated pathogen. Multivariate analysis showed geographical location and pandemic timeline as the strongest independent predictors of EEAB use. ConclusionsEEAB administration decreased as pandemic advanced, which may be the result of intensified antimicrobial stewardship efforts. Our study provides worldwide goals for antimicrobial stewardship programs in the post-COVID-19 era.