Administration Of Effective Antibiotics Research Articles

Alnustone inhibits Streptococcus pneumoniae virulence by targeting pneumolysin and sortase A

Streptococcus pneumoniae (S. pneumoniae) is a major Gram-positive opportunistic pathogen that causes pneumonia, bacteremia, and other fatal infections. This bacterium is responsible for more deaths than any other single pathogen in the world. Inexplicably, these symptoms persist despite the administration of effective antibiotics. Targeting pneumolysin (PLY) and sortase A (SrtA), the major virulence factors of S. pneumoniae, this study uncovered a novel resistance mechanism to S. pneumoniae infection. Using protein phenotype assays, we determined that the small molecule inhibitor alnustone is a potent drug that inhibits both PLY and SrtA. As essential virulence factors of S. pneumoniae, PLY and SrtA play a significant role in the occurrence of infection. Furthermore, evaluation using PLY-mediated hemolysis assay demonstrated alunstone had the potential to interrupt the haemolytic activity of PLY with treatment alunstone (4 μg/ml). Co-incubation of S. pneumoniae D39 SrtA with small-molecule inhibitors decreases cell wall-bound Nan A (pneumococcal-anchored surface protein SrtA), inhibits biofilm formation, and reduces biomass significantly. The protective effect of invasive pneumococcal disease (IPD) on murine S. pneumoniae was demonstrated further. Our study proposes a comprehensive bacteriostatic mechanism for S. pneumoniae and highlights the significant translational potential of targeting both PLY and SrtA to prevent pneumococcal infections. Our findings indicate that the antibacterial strategy of directly targeting PLY and SrtA with alnustone is a promising treatment option for S. pneumoniae and that alnustone is a potent inhibitor of PLY and SrtA.

Predictive scoring models for persistent gram-negative bacteremia that reduce the need for follow-up blood cultures: a retrospective observational cohort study

BackgroundAlthough the risk factors for positive follow-up blood cultures (FUBCs) in gram-negative bacteremia (GNB) have not been investigated extensively, FUBC has been routinely carried out in many acute care hospitals. We attempted to identify the risk factors and develop a predictive scoring model for positive FUBC in GNB cases.MethodsAll adults with GNB in a tertiary care hospital were retrospectively identified during a 2-year period, and GNB cases were assigned to eradicable and non-eradicable groups based on whether removal of the source of infection was possible. We performed multivariate logistic analyses to identify risk factors for positive FUBC and built predictive scoring models accordingly.ResultsOut of 1473 GNB cases, FUBCs were carried out in 1268 cases, and the results were positive in 122 cases. In case of eradicable source of infection, we assigned points according to the coefficients from the multivariate logistic regression analysis: Extended spectrum beta-lactamase-producing microorganism (+ 1 point), catheter-related bloodstream infection (+ 1), unfavorable treatment response (+ 1), quick sequential organ failure assessment score of 2 points or more (+ 1), administration of effective antibiotics (− 1), and adequate source control (− 2). In case of non-eradicable source of infection, the assigned points were end-stage renal disease on hemodialysis (+ 1), unfavorable treatment response (+ 1), and the administration of effective antibiotics (− 2). The areas under the curves were 0.861 (95% confidence interval [95CI] 0.806–0.916) and 0.792 (95CI, 0.724–0.861), respectively. When we applied a cut-off of 0, the specificities and negative predictive values (NPVs) in the eradicable and non-eradicable sources of infection groups were 95.6/92.6% and 95.5/95.0%, respectively.ConclusionsFUBC is commonly carried out in GNB cases, but the rate of positive results is less than 10%. In our simple predictive scoring model, zero scores—which were easily achieved following the administration of effective antibiotics and/or adequate source control in both groups—had high NPVs. We expect that the model reported herein will reduce the necessity for FUBCs in GNB cases.

188. Which patients with gram-negative bacteremia need follow-up blood cultures?

BackgroundUniversal follow-up blood culture (FUBC) in gram-negative bacteremia (GNB) is not recommended, but it has been routinely conducted in many acute-care hospitals. In contrast with Staphylococcus aureus bacteremia, risk factors for positive FUBC in GNB have not been well investigated. Therefore, we tried to identify the risk factors for and develop predictive scores of positive FUBC.MethodsAll adults (≥18 years-old) with GNB were identified in a tertiary-care hospital during the 2-year period, retrospectively. Death within 2 days of GNB and polymicrobial infection with gram-positive bacteria or fungus were excluded. GNB were classified into eradicable and non-eradicable source of infection groups, according to the possibility of source removal. We performed multivariate analyses for identifying risk factors for positive FUBC and built prediction scores using the coefficients of the multivariate logistic regression models.ResultsOf total 1,473 GNB, FUBC was drawn in 1,268 (86%) patients and 122 (9.6%) had positive results. In patients with eradicable source of infection, ESBL-producing microorganism, catheter-related bloodstream infection, unfavorable treatment response, and quick sequential organ failure assessment (qSOFA) score (≥2) were associated. On the other hand, administration of effective antibiotics and adequate source control were negatively associated with positive FUBC. In non-eradicable source of infection, end-stage renal disease on hemodialysis, and unfavorable treatment response were related to positive FUBC and administration of effective antibiotics was negatively associated (Table 1). When we built prediction scores according to the coefficients, the areas under the curves were 0.864 (95% confidence interval [CI95] 0.816–0.912) and 0.792 (CI95, 0.721–0.861), respectively. When we applied a cutoff of 0, specificities/negative predictive values in eradicable and non-eradicable source of infection groups were 84.7%/95.6% and 95.5%/95.0%, respectively (Table 2).ConclusionOur prediction scores based on adequate source control and use of effective antibiotics showed high specificities and negative predictive values. Therefore, we could expect these score systems to contribute to reducing unnecessary FUBC in GNB. Disclosures All authors: No reported disclosures.

Agr functionality affects clinical outcomes in patients with persistent methicillin-resistant Staphylococcus aureus bacteraemia.

Methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) often persists despite appropriate antibiotic therapy. It is unclear what microbiological factors contribute to poor clinical outcomes in persistent MRSAB (pMRSAB). We aimed to identify clinical and microbiological risk factors for in-hospital mortality in pMRSAB. We analysed MRSAB cases prospectively collected between 2009 and 2016 at 11 hospitals in Korea, defining cases of pMRSAB as MRSAB lasting ≥5days despite administration of effective antibiotics. The first blood isolates from the pMRSAB cases were tested for staphylococcal cassette chromosome mec type, staphylococcal protein A type, accessary gene regulator (agr) type, genes for Panton-Valentine leukocidin and phenol-soluble modulin-mec, vancomycin minimum inhibitory concentration, vancomycin heteroresistance, and agr functionality. We also collected clinical information for each case. Of 960 MRSAB cases, 152 pMRSAB were finally eligible. Univariable analysis revealed that in-hospital mortality was significantly associated with Charlson's comorbidity-weighted index (CCWI) score, Pitt bacteremia score, sequential organ failure assessment score, presentation with septic shock, pneumonia, agr dysfunction, and vancomycin heteroresistance. Bone and joint infections were negatively associated with in-hospital mortality. Multivariable analysis revealed the following independent risk factors for in-hospital mortality: CCWI score [adjusted odds ratio (aOR), per one point, 1.25; 95% confidence interval (CI), 1.08-1.44; P=0.003), Pitt bacteremia score (aOR, per one point, 1.33; 95% CI, 1.09-1.62; P=0.005), non-eradicated foci of infection (aOR, 3.12; 95% CI, 1.18-8.27; P=0.022), and agr dysfunction (aOR, 2.48; 95% CI, 1.12-5.47; P=0.025). agr dysfunction is an independent risk factor for in-hospital mortality in pMRSAB.

Bloodstream Infection with Carbapenem-resistant Klebsiella Pneumoniae and Multidrug-resistant Acinetobacter Baumannii: a Case Report

IN the presence of septic shock, every hour in delaying the administration of effective antibiotics is associated with a measurable increase in mortality. This is especially true for neutropenic patients with septic shock.1 As there is a higher incidence of involving multi-drug resistant pathogens for neutropenic patients, the decision on antibiotics regime remains a challenge for physicians.2 Immunosuppression and previous antibacterial use are factors that promote the spread of multi-drug resistant pathogens, and the possibility of co-existing multi-drug resistant pathogens should be suspected when treating patients with these risk factors who developed refractory shock. Here we present a case with neutropenic fever and refractory shock whose blood culture yielded multi-drug resistant Acinetobacter baumannii and carbapenem- resistant Klebsiella pneumoniae.

Current treatment of active infective endocarditis with brain complications

We describe the optimal timing of surgery in active infective endocarditis patients with brain complications. (1) Non-hemorrhagic infarction: elective surgery has been recommended in patients with non-hemorrhagic infarction. However, the timing is changing to an earlier phase. Recent studies have shown that silent brain embolism and small-size infarction (15-20 mm) without coma can be operated safely without delay. On the other hand, in patients with large non-hemorrhagic infarction with impaired consciousness, early surgery is not recommended. (2) Non-ruptured infectious intracranial aneurysm: treatment strategies for patients with infectious aneurysms without rupture remain controversial. However, the treatments are generally as follows. If the intracranial aneurysm without rupture decreases in size by administration of effective antibiotics, neurosurgery will not be required and cardiac surgery can be prioritized without delay. When the aneurysm without rupture enlarges and changes its morphology, neurosurgery or endovascular surgery should be prioritized to prevent its rupture. (3) Hemorrhagic stroke: this type is classified into primary intra-cerebral hemorrhage due to simple necrotic arteritis, hemorrhagic transformation of ischemic infarcts, and rupture of intracranial infectious aneurysms. Among these, primary intracerebral hemorrhage is the most frequently observed. In patients with the primary intracerebral hemorrhage, surgery must be postponed for at least 4 weeks to prevent exacerbation of bleeding. In patients with ruptured infectious aneurysm, neurosurgery or endovascular surgery is performed initially and cardiac surgery should be postponed at least 2-3 weeks.

Optimal aminoglycoside therapy following the sepsis: how much is too much?

Severe sepsis and septic shock are major problems as the result of high rates morbidity and mortality in intensive care units (ICUs). In the presence of septic shock, each hour of delay in the administration of effective antibiotics is associated with a measurable increase in mortality. Aminoglycosides are effective broad-spectrum antibiotics that are commonly used in ICUs for the treatment of life-threatening Gram-negative infections and as a part of empiric therapy for severe sepsis and septic shock. Knowledge of the pharmacokinetic (PK) and pharmacodynamic (PD) properties of the antibiotics used for the management of critically ill patients is essential for selecting the antibiotic dosing regimens and improving patient outcome. Volume of distribution (Vd) and clearance (CL) of aminoglycosides in critically ill patients differs from general population and these parameters change considerably during the therapy. Pathophysiological changes during the sepsis alter the pharmacokinetic and pharmacodynamic profile of many drugs (increase in Vd and variable changes in CL have been reported for aminoglycosides during the sepsis), therefore, dosing regimen optimization is necessary for achieving therapeutic goal, and critically ill patients should receive larger loading doses of aminoglycosides in order to achieve therapeutic blood levels and due to the considerable variation in kinetic parameters, the use of standard doses of aminoglycosides or dosing nomograms is not recommended in these populations.

Septic arthritis and acute hematogenous osteomyelitis in childhood at a tertiary hospital in Japan

The aim of the present study was to describe the clinical features of septic arthritis (SA) and acute hematogenous osteomyelitis (AHO) in children and to assess the impact of health-care-associated infections and antimicrobial resistance. A retrospective review of medical records of children presenting to Osaka City General Hospital with SA and AHO was undertaken during an 85 month period. The following data were assessed: location at onset, age and gender, risk factors, involved joints and/or bones, symptoms and time of presentation, causative agents and sensitivity to antibiotics, treatments and late complications. There were four health-care-associated (HCAI) and 20 community-acquired infections (CAI). The latency period from initial presentation to diagnosis was relatively longer in HCAI than CAI. The most common pathogen was methicillin-resistant Staphylococcus aureus (MRSA). Twenty percent of CAI patients and half of the HCAI patients were treated empirically for MRSA. All patients with complications had MRSA infection. Many pediatric patients with SA were not treated initially with optimal antibiotics. Although surgical intervention was almost inevitably required, selection and administration of effective antibiotics was necessary not only to cure the current infection but also to prevent metastatic infection. In Japan, empiric treatment of SA and AHO should include first-line antibiotics against MRSA.

Pseudoepitheliomatous hyperplasia formation after skin injury

Pseudoepitheliomatous hyperplasia (PEH) is characteristic of reactive epithelial downward proliferation into the dermis. To explore the mechanism of PEH formation, we investigated the cause, clinical characteristics, histopathologic change, and clinical treatment of PEH, the expression characteristics of stem cell factor (SCF), and its receptor c-Kit in PEH and normal skin of PEH edge (PEH-N). The clinical data of 11 patients with PEH were reviewed, and biopsy examination and bacterial cultures were performed. The histological features of PEH and expression levels of SCF, c-Kit were examined with the pathological method and immunohistochemical methods. The results showed that in each case, histological examination revealed epidermal hyperplasia with irregular cords of epithelial cells extending into the dermis. The bacteria could be cultured and isolated from all PEH biopsies. These bacteria were resistant to several antibiotics, except vancomycin. Radical excision and daily dressing with vancomycin could cure PEH. SCF protein was expressed at stronger levels in sweat gland epithelial cells and interstitial cells of the PEH group vs. the PEH-N group. c-Kit was more strongly expressed by interstitial cells in PEH than in PEH-N. It was concluded that the improper management of cutaneous wounds might cause PEH formation, which can be cured by surgical excision and administration of effective antibiotics. SCF and c-Kit might be involved in the epidermal hyperplasia observed in PEH.

Are Blood Cultures Necessary in Community-Acquired Pneumonia?

In Brief Blood cultures are included in all current community-acquired pneumonia (CAP) management guidelines. However, recent studies have cast doubt on the utility of blood cultures to affect patient outcomes. To be an effective tool, a test needs to have sufficient sensitivity and specificity in the patient group of interest to alter physician prescribing habits, and when made, those changes need to impact positively on outcome. The yield of blood cultures varies but averages 7% to 8%, with a significant (4%–5%) false positive rate. Blood cultures are more likely to be positive in patients with comorbidities (particularly liver disease, chronic obstructive pulmonary disease, alcoholism and diabetes), in patients admitted to the intensive care unit, and in patients with more abnormal vital signs at presentation. Antibiotics prior to presentation markedly reduce the likelihood of a positive blood culture. When blood culture–guided changes in treatment are made, there is little other than anecdotal evidence that outcomes are improved, possibly due to the time period between the administration of effective antibiotics and a positive impact on outcome. Clinicians’ reluctance to alter antibiotic therapy based on positive blood cultures further reduces their ability to affect outcomes. Given these limitations, blood cultures are unlikely to influence outcomes in previously well patients with less severe CAP, particularly if they have received previous antibiotic therapy. Despite these significant limitations, blood cultures are probably still advisable in patients with severe CAP due to the high mortality in this group. Blood cultures are recommended as part of most major guidelines for the management of community-acquired pneumonia (CAP), despite a number of studies challenging their usefulness. Only obtaining blood cultures from patients with a high probability of bacteremia is appealing, but in practice it has been difficult to define such a group with a high sensitivity or specificity. This article summarizes the available data on the usefulness of blood cultures in CAP.

A CASE OF FITZ-HUGH CURTIS SYNDROME DUE TO CHLAMYDIA INFECTION

A 33-year-old woman was seen at the hospital because of right hypochondralgia on September 2, 1991. On blood biochemical examination, the WBC count was 10, 200/mm3 and CRP was 4+, but no findings directly indicative of a diagnosis were obtained by ultrasound, CT, or gastroendoscopic examination. The patient developed an acute pain in the abdomen after endoscopy on September 4 and was admitted to the hospital. On September 8, genital bleeding was noted, and examination at the department of Obstetic and Gynecology disclosed right adenexitis due to Chlamydia infection. The antibiotic was changed to M1N0, and conservative therapy was sustained. However, right back pain and symptoms of peritonitis appeared, and imaging examination revealed intrapelvic abscesses and right hydronephrosis. Open abdominal drainage was carried out on September 13. The patient was diagnosed as Fitz-Hugh Curtis syndrome, because of anti-Chlamydia antibody level of 128 times, fibrous adhesion between the liver and the surrounding tissues, and the presence of right adenexitis. In this case, early diagnosis and administration of effective antibiotics are considered to have been needed. Fitz-Hugh Curtis syndrome should be included as a differential diagnosis of celiopathy in women complaining of right upper abdominal pain.