Prior Antimicrobial Therapy Research Articles

Epidemiology of pediatric meningitis and encephalitis in Japan: a cross-sectional study.

Information on the epidemiology and cause-specific clinical features of pediatric meningitis and encephalitis is limited, owing to conventional laboratory methods' limitations in identifying causative pathogens. The FilmArray Meningitis/Encephalitis (FA-M/E) panel, a molecular diagnostic tool, can detect 14 pathogens within 1 hour. We investigated meningitis and encephalitis epidemiology among children in Japan and FA-M/E panels' utility in their clinical management. This cross-sectional study was conducted among children aged 0-18 years admitted to seven regional hospitals in western Japan between October 2022 and September 2023. Cerebrospinal fluid (CSF) samples were collected from 221 children and tested using the FA-M/E panel. Clinical and microbiological data were reviewed retrospectively. Fifty-eight patients tested positive using the FA-M/E panel. Viral and bacterial pathogens were detected in 49 and nine cases, respectively. Human parechovirus and enterovirus occurred mainly in epidemic clusters during the summer and were primarily detected in young infants. Patients who tested positive for human parechovirus had a significantly higher frequency of sepsis-like manifestations and a lower frequency of CSF pleocytosis than did those who tested positive for enterovirus. CSF pleocytosis was absent in 30 patients who tested positive using the FA-M/E panel. Among the patients who tested positive for bacteria, three of the nine were not diagnosed using conventional culture methods, owing to prior antimicrobial therapy. The FA-M/E panel can identify bacterial and viral pathogens causing pediatric meningitis and characterize the epidemiology in local communities.IMPORTANCECulture and polymerase chain reactions have traditionally been used to identify microorganisms causing pediatric meningitis and encephalitis. However, the methods currently used to identify the causative microorganisms are limited, particularly in general hospitals. The FilmArray Meningitis/Encephalitis (FA-M/E) panel, a fully automated genetic testing system, can detect 14 pathogens using the multiplex polymerase chain reaction method. This study described the epidemiology of pediatric meningitis and encephalitis in Japan. The microorganisms causing acute meningitis and encephalitis in children in Japan were identified using the FilmArray Meningitis/Encephalitis panel. Testing cerebrospinal fluid using the FA-M/E panel is useful for the identification of the pathogen in children with community-acquired acute meningitis and encephalitis. This increases knowledge on the epidemiology and clinical manifestations of acute meningitis and encephalitis caused by specific pathogens and can be used to facilitate optimal patient management.

Prevalence, Risk Factors, and Outcome of Carbapenem-resistant Acinetobacter Infections in a Community Hospital in Madinah, Saudi Arabia.

Acinetobacter is a Gram-negative bacterium that causes nosocomial infections, increasing healthcare costs, patient morbidity, and mortality. The rate of carbapenem resistance among Acinetobacter species is rising in several countries, including Saudi Arabia. To determine the risk factors and compare the predictors of mortality in patients infected with carbapenem-susceptible and carbapenem-resistant Acinetobacter strains. This retrospective study included patients with Acinetobacter infection who were admitted to a community hospital in Madinah, Saudi Arabia, between January 2017 and June 2021. A logistic regression analysis was conducted to assess the risks of acquiring carbapenem-resistant Acinetobacter infections and the mortality risk associated with these infections. This study included 138 Acinetobacter-infected cases, of which 114 (82%) were carbapenem-resistant infections. Between 2017 and 2020, resistance rates increased from 75% to 87%. Patients with carbapenem-resistant Acinetobacter infections had higher 90-day mortality than those with carbapenem-susceptible infection (62% vs. 29%, P = 0.006). The risk factors for carbapenem-resistant Acinetobacter infections were prior antimicrobial therapy (aOR: 8.36 [1.69-41.29]; P = 0.009) and mechanical ventilation (aOR: 6.07 [1.82-20.20]; P = 0.003). Among all patients with Acinetobacter infections, significant predictors of 90-day mortality were carbapenem resistance (aOR: 3.26 [1.19-8.90]; P = 0.021) and Charlson comorbidity score (aOR: 1.19 [1.06-1.34]; P = 0.004). The increase in carbapenem-resistant Acinetobacter cases in this study was consistent with the findings of other studies from Saudi Arabia. This, together with the high associated mortality rates, indicates the urgent need for effective antimicrobials and infection prevention strategies to combat carbapenem-resistant Acinetobacter infections in hospitals.

Culture-Negative Native Vertebral Osteomyelitis: A Narrative Review of an Underdescribed Condition.

The incidence of culture-negative NVO (CN-NVO) cases is increasing, presenting significant diagnostic and therapeutic challenges due to the inability to isolate causative organisms with conventional microbiological methods. Factors influencing the diagnosis of CN-NVO include prior antimicrobial therapy, low pathogen burden, fastidious or intracellular organisms, technical issues, and non-infectious mimickers. Diagnosis often relies on imaging modalities like magnetic resonance imaging (MRI) and computed tomography (CT)-guided biopsy, though these methods can sometimes fail to yield positive microbiological results. Advanced diagnostic tools, such as polymerase chain reaction (PCR), metagenomic next-generation sequencing (mNGS), and cell-free DNA analysis, may be necessary to identify the pathogen. The causative pathogen cannot be isolated in some patients, among which an empirical antimicrobial therapy should be initiated. This narrative review discusses the management, monitoring, surgical indications, and outcomes for patients with CN-NVO.

Non-carbapenem Drugs for Patients with Bacteremia caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: Piperacillin-Tazobactam

Background/Aims: Carbapenems are recommended for treating bacteremia caused by extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae (ESBL-E). However, this has resulted in a significant rise in the utilization of carbapenems in cases of ESBL-E infection. We evaluated the clinical outcomes of patients with ESBL-E bacteremia treated with non-carbapenem antimicrobials.Methods: We conducted a retrospective case-control study of a cohort of patients with documented ESBL-E bacteremia from January 2021 to December 2021. The patients were divided into two groups according to whether they received non-carbapenem or carbapenem therapy. The rates of treatment failure, 30-day mortality and microbiologic failure, and the durations of hospitalization and of antimicrobial therapy were compared between the two groups. Antimicrobial susceptibility testing and phenotypic identification of ESBL-E were performed using the Vitek 2 system.Results: Of 118 patients with ESBL-E bacteremia, 54 received non-carbapenem drugs (non-carbapenem group [NCG]) and 64 received carbapenems (carbapenem group [CG]). Treatment failure at 30 days occurred in 16.7% of the patients in the NCG and in 18.8% in the CG (p = 0.65). The 30-day mortality rate was 14.8% in the NCG and 17.2% in the CG (p = 0.63). Extra-urinary tract infection and prior antimicrobial therapy within 30 days were risk factors for treatment failure in patients with ESBL-E bacteremia. The clinical outcomes did not differ significantly between the two groups, challenging the prevailing preference for carbapenems in the treatment of ESBL-E bacteremia.Conclusions: Non-carbapenem antimicrobials such as piperacillin/tazobactam are recommended for patients with mild ESBL-E bacteremia in South Korea.

Clinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung

Hospital-acquired pneumonia (HAP) is associated with high mortality and costs, and frequently caused by multidrug-resistant (MDR) bacteria. Although prior antimicrobial therapy is a major risk factor for HAP, the underlying mechanism remains incompletely understood. Here, we demonstrate that antibiotic therapy in hospitalized patients is associated with decreased diversity of the gut microbiome and depletion of short-chain fatty acid (SCFA) producers. Infection experiments with mice transplanted with patient fecal material reveal that these antibiotic-induced microbiota perturbations impair pulmonary defense against MDR Klebsiella pneumoniae. This is dependent on inflammatory monocytes (IMs), whose fatty acid receptor (FFAR)2/3-controlled and phagolysosome-dependent antibacterial activity is compromized in mice transplanted with antibiotic-associated patient microbiota. Collectively, we characterize how clinically relevant antibiotics affect antimicrobial defense in the context of human microbiota, and reveal a critical impairment of IM´s antimicrobial activity. Our study provides additional arguments for the rational use of antibiotics and offers mechanistic insights for the development of novel prophylactic strategies to protect high-risk patients from HAP.

Reviving Sternheimer stain: A single-center retrospective study to detect the diagnostic utility of urinary tract infections in the emergency department

IntroductionQualitative urinalysis using the Sternheimer stain is a common method in Japan for identifying bacteriuria, but there is a lack of studies examining its test characteristics. In this study, we aimed to investigate the sensitivity and specificity of the Sternheimer stain for urine culture results and compare it with the sensitivity and specificity of the Gram stain. Our goal was to determine the usefulness of the Sternheimer stain in identifying bacteriuria. Patients and methodsAmong 986 patients aged 16 years or older from whom samples for both urinalysis and urine culture were obtained at the emergency room of Tenri Hospital from January 2019 to December 2019, 342 patients with pyuria, defined as the presence of 10 or more white cells per cubic millimeter in a urine specimen, who had not received prior antimicrobial therapy were included. Urine cultures were used for comparison to determine the sensitivity and specificity of Sternheimer and Gram stain in this patient group. A positive Sternheimer stain result was defined as bacteriuria ≥ (1+), and that of Gram stain was defined as ≥ 1/1 field of high-power ( × 1000) oil immersion. ResultsUsing urine culture results for comparison, the sensitivity of Sternheimer stain was 92.2%, the specificity was 48.5%, the positive likelihood ratio was 1.79, and the negative likelihood ratio was 0.16. DiscussionSternheimer stain is a rapid and useful method to exclude bacteriuria in a group of patients with pyuria in the emergency department.

Validation of a multiplex-tandem RT-PCR for the detection of bovine respiratory disease complex using Scottish bovine lung samples

The welfare and economic impact of bovine respiratory disease complex (BRDC), and its associated antibiotic usage, are major challenges to cattle rearing and beef cattle finishing industries. Accurate pathogen diagnosis is important to undertake appropriate treatment and long-term management strategies, such as vaccine selection. Conventional diagnostic approaches have several limitations including high costs, long turnaround times and difficulty in test interpretation, which could delay treatment decisions and lead to unnecessary animal losses. We describe the validation of a multiplex-tandem (MT) reverse transcription-polymerase chain reaction (RT-PCR) for the detection of seven common pathogens associated with BRDC. This test has the potential to advance pathogen identification and to overcome many of the limitations of current testing methods. It requires a single sample and results are obtained quickly and not influenced by prior antimicrobial therapy or overgrowth of contaminating organisms. We demonstrated a test specificity of 100% and sensitivity ranging from 93.5% to 100% for these seven common pathogens. This test will be a useful addition to advance BRDC investigation and diagnosis.

Viral etiology of lower respiratory tract infections in adults in the pre-COVID-19 pandemic era: A cross-sectional study in a single center experience from Cameroon.

Respiratory viruses are responsible for the majority of lower respiratory tract infections (LRTIs) worldwide. However, there is a gap on the epidemiology of viral LRTIs in adults in sub-Saharan African countries. In Cameroon, like in other countries, the role of viral respiratory pathogens in the etiology of LRTIs in adults is helpful for clinical management. This study aimed to determine the viral aetiologies of LRTIs among hospitalized adults in a reference center for respiratory diseases in the town of Yaounde in Cameroon and its surroundings. A cross-sectional study was conducted from January 2017 to January 2018 at Jamot Hospital in Yaounde (Cameroon). Clinical and demographic information; BAL and sputa were collected from hospitalized patients meeting LRTI case definitions. The clinical samples were investigated for respiratory pathogens with a commercial Reverse Transcriptase Real-Time Polymerase Chain Reaction (RT-PCR) targeting 21 viruses, cultures for bacterial and fungal infections. The 77 included adult patients with LRTIs had an appropriate clinical sample for microbial investigations. A viral agent was detected in 22.1% (17/77) samples. The main viruses detected included rhinovirus (10/77), coronavirus (hCoV-OC43 and hCoV-229E), and influenza A virus (3/77 each). A concomitant viral and bacterial co-infection occurred in 7.8% of patients (6/77) while viral co-infection occurred in one patient (1.3%). No Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) was detected in clinical samples. Most patients were under antimicrobials before getting diagnosed. Respiratory viruses account for 22.1% of LRTIs in hospitalized patients in this study. Despite prior antimicrobial therapy and delay, rhinovirus, coronavirus and influenza A virus were the most detected in patients in the pre-COVID-19 pandemic era in a single center experience from Cameroon.

Post ventriculoperitoneal shunting S. Maltophilia Meningitis

Background: Leptomeningeal inflammation caused by S. Maltophilia is rare. It is inextricably linked with prior antimicrobial therapy, prolonged ICU stays and antecedent neurosurgical intervention. Case description: We describe a case of a 5-year-old male child with posterior fossa medulloblastoma with obstructive hydrocephalus who underwent ventriculoperitoneal shunt followed by suboccipital midline craniotomy and later presented with S. Maltophilia meningitis. Conclusion: The overall mortality in the cases reviewed was 17 per cent. Inherent resistance to a wide array of antimicrobial agents with a simultaneously increasing number of cases poses a therapeutic challenge. Trimethoprim/sulfamethoxazole is recommended as empirical and as a definitive treatment in patients with S. Maltophilia infection. The optimal duration of therapy for S. Maltophilia meningitis is similar to the treatment of gram-negative bacillary meningitis, which is usually 2 weeks after the culture has been negative.

Occurrence and characterization of methicillin-resistant Staphylococcus spp. in diseased dogs in Brazil.

Staphylococcus pseudintermedius is a major commensal bacterium of the skin and mucosae of dogs and an opportunistic agent responsible for several clinical infections, such as pyoderma, otitis, and surgical wound infections. The emergence of methicillin-resistant S. pseudintermedius (MRSP) has become a problem of great concern in veterinary and human medicine because it is multidrug resistant (MDR) and can also infect humans. This study aimed to identify the occurrence of Staphylococcus spp. in infected patients and investigate the antimicrobial resistance profiles and molecular structure of MRSP isolates. Samples were obtained from two different veterinary clinics; suggestive colonies were submitted to matrix-assisted laser desorption ionization-time of flight (MALDI-ToF) mass spectrometry and confirmed at the species level by polymerase chain reaction (PCR). Sequencing of the 16S rRNA and rpoB genes were used in selected samples that were not identified by MALDI-ToF and by the species-specific PCR. Antimicrobial susceptibility and PCR detection of mecA were performed. MRSP isolates were subjected to multilocus sequence typing. Of all the clinical staphylococci (n = 131), 98 (74.8%) were identified as S. pseudintermedius. Multidrug resistance (resistance to ≥3 classes of antimicrobials) was observed in 63.2% of S. pseudintermedius isolates, and 24.5% of S. pseudintermedius isolates were methicillin-resistant. Half of the MRSP isolates were isolated from surgical site infections. Among the ten sequence types (ST) identified, nine were novel. ST71 was the most prevalent and associated with resistance to fluoroquinolones. Prior antimicrobial therapy, hospitalization, and surgical site infections seemed to be risk factors for MRSP acquisition. The present study showed a high rate of MDR staphylococci in infected dogs. MRSP was isolated from different clinical conditions, mainly surgical site infections. Additionally, this is the first study to extensively investigate the population structure of MRSP in Brazil, which revealed the dispersion of CC71 and nine novel ST. These findings raise concerns for both animal and human health due to the zoonotic potential of this species and limited therapeutic options available for MRSP infections.

Nosocomial Pneumonia in the Mechanically Ventilated Patient.

Ventilator-associated pneumonia (VAP) is a common complication occurring in critically ill patients who are mechanically ventilated and is the leading cause of nosocomial infection-related death. Etiologic agents for VAP widely differ based on the population of intensive care unit patients, duration of hospital stay, and prior antimicrobial therapy. VAP due to multidrug-resistant pathogens is associated with the highest morbidity and mortality, likely due to delays in appropriate antimicrobial treatment. International guidelines are currently available to guide diagnostic and therapeutic strategies. VAP can be prevented through various pharmacological and non-pharmacological interventions, which are more effective when grouped as bundles. When VAP is clinically suspected, diagnostic strategies should include early collection of respiratory samples to guide antimicrobial therapy. Empirical treatment should be based on the most likely etiologic microorganisms and antibiotics likely to be active against these microorganisms. Response to therapy should be reassessed after 3 to 5 days and antimicrobials adjusted or de-escalated to reduce the burden of the disease. Finally, considering that drug resistance is increasing worldwide, several novel antibiotics are being tested to efficiently treat VAP in the coming decades.

Empiric antimicrobial therapy for early-onset pneumonia in severe trauma patients.

The bacterial ecology involved in early pneumonia of severetrauma patients is mostly commensal and would allow wide use of narrow-spectrum antibiotics. We describe risk factors for treatment failure of severe trauma patients' pneumonia with the use of narrow-spectrum antimicrobial therapy in orderto develop a score that could help clinicians to determine which patients might be treated with narrow-spectrum antibiotics. A retrospective, observational, monocentric cohort study was conducted of severe trauma patients requiring mechanical ventilation for > 48h and developing a first episode of microbiologically confirmed pneumonia occurring within the first 10 days after admission. Overall, 370 patients were included. The resistance rate against narrow-spectrum antibiotics (amoxicillin/clavulanic acid) was 22.7% (84 pneumonia). In a multivariate analysis, two independent risk factors were associated with this resistance: prior antimicrobial therapy ≥ 48h (OR 4.00; 95 CI [2.39; 6.75]) and age ≥ 30y (OR 2.10; 95 CI [1.21; 3.78]). We created a prediction score that defined patient with one or two risk factors at high risk of resistance. This score presented a sensitivity of 0.92 [0.88; 0.94], a specificity of 0.33 [0.28; 0.38], a positive predictive value of 0.29 [0.24; 0.33] and a negative predictive value of 0.93 [0.90; 0.95]. Simple risk factors may help clinicians to identify severe trauma patients at high risk of pneumonia treatment failure with the use of narrow-spectrum antimicrobial therapy and, thus, use better tailored empiric therapy and limit the use of unnecessary broad-spectrum antimicrobial therapy.

Clinical characteristics and risk factors for culture-negative periprosthetic joint infections

BackgroundCulture-negative periprosthetic joint infections (PJIs) can complicate diagnosis and management of PJI. This study aimed to identify risk factors for culture-negative PJI and differences in clinical characteristics between culture-positive and culture-negative PJI group.MethodsThis retrospective, cross-sectional study evaluated PJI cases obtained between January 2013 and October 2019 at our institution. These PJI cases were divided into culture-positive and culture-negative groups and then compared. The demographics, laboratory findings, and details of patient’s clinical characteristics were investigated. Univariate and multivariate logistic regression analysis were performed to investigate risk factors for culture-negative PJI.ResultsA total of 109 PJI cases were included in the analysis: 82 (75%) culture-positive and 27 (25%) culture-negative. The mean serum white blood cell (WBC) count, C-reactive protein level, and erythrocyte sedimentation rate in the culture-negative group were significantly lower than those in the culture-positive group (p < 0.05). There were no significant differences between the two groups regarding history of prior antibacterial administration or treatment success rates. Multivariate analysis identified a low serum WBC count as a risk factor for culture-negative PJI (odds ratio = 0.78; 95% confidence interval [CI] = 0.63–0.97; p = 0.027).ConclusionsA low serum WBC count is a risk factor for culture-negative PJI, but prior antimicrobial therapy is not. The results suggest that PJI cases with lower levels of systemic inflammation are likely to be culture-negative; therefore, the possibility of a culture-negative result should be considered in suspected cases of PJI with low inflammatory markers, regardless of prior antibiotic exposure.

Polymicrobial Pseudomonas Plus Candida Parapsilosis Endocarditis in an Injection Drug User: Considerations for Diagnosis and Management

Fungal endocarditis (FE) is a potentially lethal condition and its diagnosis can be challenging due to the low yield from blood cultures. FE should be suspected in patients with associated risk factors despite the identification of positive bacterial blood cultures. The common risk factors for FE discussed in the literature are total parenteral nutrition, immune suppression, prior antimicrobial therapy, intravenous drug addiction, and cardiac surgery. In this report, we discuss a patient who had positive blood cultures for Pseudomonas but was found to have Candida parapsilosis on valve culture. Physicians need to maintain a high index of suspicion for co-infective endocarditis in this patient population.

Multicenter Evaluation of the Unyvero Platform for Testing Bronchoalveolar Lavage Fluid

Bronchoalveolar lavage (BAL) culture is a standard, though time-consuming, approach for identifying microorganisms in patients with severe lower respiratory tract (LRT) infections. The sensitivity of BAL culture is relatively low, and prior antimicrobial therapy decreases the sensitivity further, leading to overuse of empirical antibiotics. The Unyvero LRT BAL Application (Curetis GmbH, Germany) is a multiplex molecular panel that detects 19 bacteria, 10 antibiotic resistance markers, and a fungus, Pneumocystis jirovecii, in BAL fluid in ∼4.5 h. Its performance was evaluated using 1,016 prospectively collected and 392 archived specimens from 11 clinical trial sites in the United States. Overall positive and negative percent agreements with culture results for identification of bacteria that grow in routine cultures were 93.4% and 98.3%, respectively, with additional potential pathogens identified by Unyvero in 21.7% of prospectively collected specimens. For detection of P. jirovecii, the positive percent agreement with standard testing was 87.5%. Antibiotic resistance marker results were compared to standard antibiotic susceptibility test results to determine positive predictive values (PPVs). PPVs ranged from 80 to 100%, based on the microorganism and specific resistance marker(s). The Unyvero LRT BAL Application provides accurate detection of common agents of bacterial pneumonia and of P. jirovecii The sensitivity and rapidity of this panel suggest significant clinical value for choosing appropriate antibiotics and for antibiotic stewardship.

Predominance of Non-carbapenemase Producing Carbapenem-Resistant Enterobacterales in South Texas.

BackgroundCarbapenem-resistant Enterobacterales (CRE) pose a significant global public health threat. Resistance among CRE is particularly complex, owing to numerous possible resistance mechanisms and broad definitions. We aimed to characterize the clinical and molecular profiles of CRE in the South Texas region.Materials and methodsWe compared the clinical, genotypic, and phenotypic profiles of carbapenemase producing Enterobacterales (CPE) with those of non-carbapenemase producers (NCPE) isolated from South Texas, United States between 2011 and 2019. Molecular characteristics and resistance mechanisms were analyzed using whole-genome sequences.ResultsThe majority (59%) of the CRE isolates were NCPE while 41% of isolates harbored carbapenemases, predmonantly blaKPC-type. The most common CPE was Klebsiella pneumoniae while majority of Enterobacter cloacae and Escherichia coli were NCPE Among K. pneumoniae, the clonal group 307 has emerged as a predmoninant group and was associated with as many CRE infections as the previous common clonal group 258. Patients with NCPE compared to CPE infections were associated with higher antimicrobial exposure prior to culture collection (days of therapy, 795 vs. 242; p < 0.001) and emergency department visits within past 90 days (22% vs. 4%; p = 0.011). The all cause 30-day mortality was 21%.ConclusionsThis study highlights the diversity of resistance mechanisms underlying CRE in South Texas, with 59% not harboring a carbapenemase. Individuals with NCPE infections were more likely to have had prior antimicrobial therapy and emergency department visits compared to those with CPE. Identification and distinction of these mechanisms by rapid identification of species and carbapenemase would allow for optimal treatment and infection control efforts.

Healthcare-associated ventriculitis: current and emerging diagnostic and treatment strategies

ABSTRACT Introduction: Healthcare-associated ventriculitis and meningitis occur after neurosurgical procedures, is associated with an adverse outcome in the majority of patients and represent a diagnostic challenge to clinicians. As the cerebrospinal fluid (CSF) culture is the cornerstone of diagnosis, obtaining CSF studies prior to starting antibiotic therapy is key. Areas covered: This review will evaluate the incidence, risk factors, clinical presentation, diagnosis, empirical intravenous antibiotic therapy, adjunctive intrathecal therapy, microbiology, prognosis, and prevention of HCAVM. We highlight the challenges and limitations of the currently available diagnostic methods and definitions and explore novel technologies. Our review included the search for published literature until June 2020. Expert opinion: Despite available preventive measures, HCAVM continues to occur and to be independently associated with significant neurological morbidity and mortality in the majority of patients. The cornerstone of the diagnosis of HCAVM is a positive CSF culture but the microbiological yield is reduced to ~50% with prior antimicrobial therapy. Although the CSF profile is not affected by antibiotic therapy it has a fair diagnostic accuracy. Future research efforts should concentrate in identifying novel diagnostic tools such as polymerase chain reaction (PCR) or metagenomic sequencing.

Evaluation of the pneumococcal urinary antigen test (PUT): a retrospective study.

To determine the usefulness of the pneumococcal urinary antigen test (PUT) and to describe the characteristics of pneumococcal pneumonia. In this retrospective study, we examined the effects of prior antibiotic treatment, pneumonia onset period, and sputum quality on the results of PUT. Clinical information was collected via medical records from all adult patients who were hospitalized at the Fujita Health University Bantane Hospital with "pneumonia" as a new diagnosis from April 2015 to March 2018. A total of 482 patients with pneumonia were included, of whom 103 had pneumococcal pneumonia. The frequency of PUT positivity did not differ significantly in patients with a pneumonia onset period of ≥3 days compared with those with a period of ≤2 days (P=0.514). Patients with a history of prior antimicrobial therapy had a significantly lower rate of positive sputum culture vs those with no such history (P=0.005); however, PUT positivity in the two groups did not differ significantly (P=0.367). Our results showed that urinary antigen testing for pneumococcal pneumonia is useful for diagnosis regardless of prior antibiotic treatment and time since symptom onset.

Clinical Experience with Telavancin for the Treatment of Patients with Bacteremia and Endocarditis: Real-World Results from the Telavancin Observational Use Registry (TOUR™).

BackgroundBacteremia and endocarditis caused by Staphylococcus aureus (S. aureus), particularly methicillin-resistant S. aureus (MRSA), are challenging to treat and are associated with high morbidity and mortality. Telavancin is a lipoglycopeptide antibacterial active against susceptible Gram-positive pathogens, including MRSA.ObjectiveThis registry study assessed the real-world use and clinical outcomes of telavancin in patients with bacteremia or endocarditis enrolled in the Telavancin Observation Use Registry (TOUR™).MethodsThe subset of patients enrolled in TOUR who were diagnosed with endocarditis and/or bacteremia with a known or unknown primary source (N = 151) were analyzed. Data including demographics, infection type, baseline pathogens, prior or concomitant antimicrobial therapy, dosing regimen, clinical response, treatment-emergent adverse events (TEAEs) of interest, and mortality were collected by retrospective medical chart review.ResultsTelavancin was primarily used as a second-line or greater therapy (n = 132, 87.4%). MRSA was present in 87 (57.6%) patients. Median telavancin dose was 740.6 mg (interquartile range (IQR) 206.0 mg) and median duration of therapy was 9.0 days (IQR 24.0 days). Of the 132/151 (87.4%) patients with an available assessment at the end of telavancin therapy, a positive clinical response was achieved in 98/132 (74.2%), while 14/132 (10.6%) failed therapy and 20/132 (15.2%) had an indeterminant outcome. TEAEs occurred in 24 (15.9%) patients. The most frequent TEAE was renal failure (n = 12, 7.9%); seven of these patients were receiving concomitant nephrotoxic medications. There was no change in creatinine clearance for 67/89 (75.3%) patients with values recorded at the beginning and the end of telavancin therapy.ConclusionsIn real-world clinical practice, overall positive clinical outcomes are observed in patients with bacteremia or endocarditis treated with telavancin, including in those patients infected with MRSA or another S. aureus pathogen. Telavancin may be an alternative treatment option for these patients.Trial RegistrationThis trial was registered with clinicaltrials.gov (NCT02288234) on 11 November 2014.Electronic supplementary materialThe online version of this article (10.1007/s40801-020-00191-x) contains supplementary material, which is available to authorized users.

Calculated initial parenteral treatment of bacterial infections: Sepsis.

This is the eleventh chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.Sepsis, defined as a life threatening organ dysfunction caused by a misregulated host response to an infection, is the third leading cause of death in Germany with a lethality rate of 30% to over 50%. An early, effective antimicrobial therapy is, next to infectious source control, the most important causal treatment option. It should be complemented by the mainly supportive measures of general intensive care therapy. Prior antimicrobial therapy, the patient’s medical history (e.g. risk factors for multiresistant agents) and small-scale epidemiology are to be considered as part of the therapeutic and practical decisions. A modification of the often needed broad initial calculated combination therapy is desirable. In the future, prompt measurements of plasma concentrations of antiinfectives, especially for the sepsis patient with diverse and partly conflicting pathophysiological changes, will have great importance regarding efficacy, toxicity and resistance development. In order to apply those complex strategies in clinical routine, there is a requirement for a strong interdisciplinary collaboration between the intensive care unit, clinical infectiology, microbiology, and clinical pharmacology, ideally in the framework of a functional antimicrobial stewardship program.