Combination Of Broad-spectrum Antibiotics Research Articles

Incidence, Clinical Profile, and Management of Keratitis Caused by Uncommon Species of Pseudomonas at a Tertiary Eye Care Center.

The purpose of this study was to study the incidence, demographic features, clinical course, profiling, and management of uncommon species of Pseudomonas keratitis (other than Pseudomonas aeruginosa ) at a tertiary eye care center. Thirty cases of culture-proven uncommon species of Pseudomonas keratitis between January 2017 and December 2021 were retrospectively studied. The incidence, demographic and clinical profile, predisposing factors, microbial results, treatment, and visual outcomes were analyzed. We evaluated the risk factors for poor treatment outcomes. Among bacterial keratitis cases, uncommon species of Pseudomonas keratitis occurred at a rate of 2.2%. The mean age at presentation was 51.37 years, and the most common predisposing factor was corneal trauma (36.7%). The mean best corrected visual acuity (BCVA) [in log of minimum angle of resolution (logMAR)] at presentation was 1.99, and the mean ulcer size was 5.75 mm. On culture, 56.7% of the cases were identified as Pseudomonas putida , 26.7% as Pseudomonas stutzeri , 10% as Pseudomonas mendocina, and 3.3% each of Pseudomonas oryzihabitans and Pseudomonas alcaligenes . We recorded good treatment responses in 66.7% of cases with the medical therapy of a combination of broad-spectrum antibiotics, whereas 33.3% of cases required surgical intervention. The risk factors for poor clinical outcome were older age, ocular trauma, previous ocular surgeries, poor BCVA at presentation, large ulcer size, delayed treatment, hypopyon, and early complications such as perforation, limbal involvement, and total ulcer. Uncommon species of pseudomonas keratitis was more closely related to predisposing factors such as corneal trauma and other factors such as previous ocular surgeries, older age, large ulcers, longer duration of treatment, early surgical intervention in complicated cases, and poor visual outcome.

Antibiotic Stewardship in Treatment of Osteoarticular Infections Based on Local Epidemiology and Bacterial Growth Times.

Incubation for 14 days is recommended for the culture of microorganisms from osteoarticular infections (OAI), but there are no recommendations for postoperative antibiotic stewardship concerning empirical antimicrobial therapy (EAT), while prolonging broad-spectrum EAT results in adverse effects. The aim of this study was to describe the local OAI epidemiology with consideration of bacterial growth times to determine which antibiotic stewardship intervention should be implemented in cases of negative culture after 2 days of incubation. We performed a 1-year, single-center, noninterventional cohort study at the Pitié-Salpêtrière hospital OAI reference center. Samples were taken as part of the local standard of care protocol for adult patients who underwent surgery for OAI (native or device related) and received EAT (i.e., piperacillin-tazobactam plus daptomycin [PTD]) following surgery. The time to culture positivity was monitored daily. Overall, 147 patients were recruited, accounting for 151 episodes of OAI, including 112 device-related infections. Microbiological cultures were positive in 144 cases, including 42% polymicrobial infections. Overall, a definitive microbiological result was obtained within 48 h in 118 cases (78%) and within 5 days in 130 cases (86%). After 5 days, only Gram-positive bacteria were recovered, especially Cutibacterium acnes, Staphylococcus spp., and Streptococcus spp. Overall, 90% of culture-positive OAI were correctly treated with the locally established EAT. EAT guidance for OAI was in agreement with our local epidemiology. Our results supported antibiotic stewardship intervention consisting of stopping piperacillin-tazobactam treatment at day 5 in cases of negative culture. IMPORTANCE Osteoarticular infections (OAI) remain challenging to diagnose and to treat. One of the issues concerns postoperative empirical antimicrobial therapy (EAT), which is usually a combination of broad-spectrum antibiotics. This EAT is maintained up to 2 weeks, until the availability of the microbiological results (identification and drug susceptibility testing of the microorganisms responsible for the OAI). Our results provide new data that will help to improve OAI management, especially EAT. Indeed, we have shown that antibiotic stewardship intervention consisting of stopping the antibiotic targeting Gram-negative bacteria included in the EAT could be implemented in cases where culture is negative after 5 days of incubation. The benefits of such an antibiotic stewardship plan include improved patient outcomes, reduced adverse events (including Clostridioides difficile infection), improvement in rates of susceptibilities to targeted antibiotics, and optimization of resource utilization across the continuum of care.

Infecciones por anaerobios de piel y partes blandas, orofaringe y parénquima pulmonar

Anaerobic bacteria are a fundamental component of the microbiota of human mucosa, especially of the mouth, lower gastrointestinal tract, and vagina. Infections that occur tend to be related to the alteration of natural barriers present in these structures or the onset of tissue ischemia, as these bacteria need a low potential of reduction–oxidation for their development. Its pathogenesis also includes the development of virulence factors, the capacity of some species to resist oxygenated microenvironments, synergism with other bacteria, and resistance to certain antibiotics. This type of infection tends to be polymicrobial, which complicates their isolation. The MALDI-TOF method has facilitated the rapid, reliable identification of these microorganisms and is currently the method of choice. The first diagnostic approach is clinical; anatomical location plays a very important role in it. Treatment tends to include a combination of broad-spectrum antibiotics along with a surgical approach in many cases. The involvement of anaerobic germs should be suspected in some infections of the skin and soft tissues, oropharynx and adjacent structures, and pulmonary parenchyma. These infections entail high morbidity and mortality. Knowledge of clinical syndromes with anaerobic involvement in these localizations facilitates a correct diagnosis and suitable treatment.

Outcome and Risk Factors of Febrile Episodes Treated with Broad Spectrum Antibiotics and Polyclonal IgM–Enriched Immunoglobulin in Pediatric Oncology Hematology Patients: A Retrospective Study

Abstract Objective Preparations with high-titer immunoglobulin-M (HT-IgM) have been used to treat neonatal and adult sepsis as adjuvant to antibiotics. Limited data are available of this use in pediatric oncohematological patients. We retrospectively assessed the characteristics and outcome of febrile episodes treated with broad-spectrum antibiotics and HT-IgM. Methods This study included febrile episodes diagnosed after chemotherapy or hematopoietic stem cell transplantation (HSCT) treated with antibiotics and HT-IgM. Study period was from January 2011 to March 2019. Results Seventy febrile episodes in 63 patients were eligible. In 40% of episodes (n = 28), blood cultures identified a causative organism: Gram-negative (n = 15), Gram-positive (n = 8), polybacterial (n = 4), fungi (n = 1). Twenty-six percent of Gram-negatives were extend spectrum β-lactamase (ESBL)-producers. In 44% of episodes, a deep-organ localization was present, mostly pulmonary. Severe or profound neutropenia, hypotension, and hypoxemia were present in 89, 26, and 21% of episodes, respectively; 20% of episodes required intensive care and 20% of episodes required the use of inotropes. Overall, 90-day mortality was 13% and infection-attributable mortality resulted 8.6%. More than half of the patients received HT-IgM within 24 hours from fever onset. HT-IgM-related allergic reactions occurred in three episodes. Risk factors for 90-day mortality were as follows: hypotension and hypoxemia at fever presentation, admission to intensive care unit (ICU), use of inotropes, presence of deep-organ infection, and escalation of antibiotic therapy within 5 days. Conclusion The combination of broad-spectrum antibiotics and HT-IgM was feasible, tolerated, and promising, being associated with a limited infectious mortality. Further prospective controlled studies are needed to assess the efficacy of this combination over a standard antibiotic approach.

Spontaneous rupture of liver abscess with biliary communication presenting as a lumbar mass

Pyogenic liver abscess was first reported in the writings of Hippocrates, which was based on the type of fluid recovered from the abscess related to a high mortality rate ranging between 15% and 19% at that time. However in 1938, Ochsner and De Bakey described the recommended surgical treatment as the primary treatment modality. Surgery remained the therapy of choice until the mid-1980s, when percutaneous drainage was shown to be a safer alternative in many cases. Spontaneous rupture of liver abscess may occur free in the peritoneal cavity or in neighbouring organs, an event which is generally considered as a surgical emergency, while localized rupture can be managed with drainage, either percutaneous or surgical/minimal invasive techniques and addition of appropriate antibiotic treatment. In cases where there is uneventful rupture of abscess and localized to the neighbouring organs and tissues can be successfully treated by a combination of broad-spectrum antibiotics and percutaneous drainage and endoscopic management.

Treatment with broad-spectrum antibiotics upregulates Sglt1 and induces small intestinal villous hyperplasia in mice.

Although extensive evidence indicates that the gut microbiota plays a crucial role in regulating glucose homeostasis, the exact regulatory mechanism remains unclear. This study aimed to investigate the effect of broad-spectrum antibiotics on the expression of glucose transporters, histomorphology of the small intestine, and glucose metabolism in mice. C57BL/6 mice were administered drinking water with or without a broad-spectrum antibiotic combination for 4 weeks. Thereafter, an oral glucose tolerance test was performed. Body weight, small intestine histopathology, mRNA levels of glucose transporters (SGLT1 and GLUT2) and intestinal transcription factors (CDX1 and CDX2) were evaluated. SGLT1 and CDX1 were upregulated in the small intestine upon antibiotic administration compared with that in the control group. The height and surface area of the jejunal villi were significantly higher upon antibiotic administration than in the control group. Fasting glucose levels were significantly higher upon antibiotic administration than in the control group. The present results indicate that treatment with broad-spectrum antibiotics upregulates SGLT1 and CDX1 and induces hyperplasia in the small intestine, thus increasing fasting blood glucose levels. Our results further the current understanding of the effects of broad-spectrum antibiotics on the gut microbiota and glucose homeostasis that may have future clinical implications.

Particulars of Medical and Surgical Treatment of Liver Abscess in Septic Patient– Case Report

Abstract First described by Bright in 1836, who reports two cases secondary to suppurative angiocolitis and pilephlebitis, intrahepatic suppurations were, until the era of the discovery of antibiotics, one of the most dreaded causes of mortality, reaching a rate of almost 100%. Today, both the incidence of liver abscesses and the mortality rate have been significantly reduced, as the introduction of antibiotics has dramatically reduced the number of septic piles due to peritoneal outbreaks. Their etiology is more recently, most frequently, a biliary or neoplastic disease. On the other hand, the improvement of germ isolation techniques has made it possible to identify anaerobic germs with maximum frequency, and diagnostic and treatment performance has increased so much with the advent of non-invasive or minimally-invasive procedures that the overall mortality rate of 70% in 1975 is now about 30–38%. We present the case of a 75-year-old male patient with no known history of ilnesses who is admitted for fever, chills, myalgia, arthralgia and visual disturbances with onset of approximately one week. Biologically he presents with leukocytosis with marked neutrophilia, mild thrombocytopenia and significant biological inflammatory syndrome. Suspicion is raised for a diagnosis of Sepsis with unspecified starting point with possible pyogenic cavernous sinus thrombosis, a complication suggested by the presence of visual disturbances. Neuro-imaging evaluation by CT and brain MRI is performed, with the diagnosis of thrombosis being refuted. Abdominal CT is performed which identifies a space replacement formation in the left hepatic lobe for which MRI evaluation is required. MRI detects an expansive hepatic formation with semiology suggestive of liver abscess. Treatment was instituted with a combination of broad-spectrum antibiotics and antifungal treatment, but the evolution was unfavourable with maintenance of leukocytosis with marked neutrophilia and progression of inflammatory samples. It was necessary to evaluate the case by a multidisciplinary team (infectious disease specialist, gastroenterologist, surgeon) to establish the appropriate therapeutic management, with surgical resolution of the case, with a favourable postoperative evolution.

Prevotella Induces the Production of Th17 Cells in the Colon of Mice.

Th17-mediated mucosal inflammation is related to increased Prevotella bacterial abundance. The actual involvement of Prevotella in the development and accumulation of intestinal Th17 cells at a steady state, however, remains undefined. Herein, we investigated the role of Prevotella in inducing intestinal Th17 cells in mice. Mice were treated with a combination of broad-spectrum antibiotics (including ampicillin, neomycin sulfate, vancomycin hydrochloride, and metronidazole) in their drinking water for 4 weeks and then gavaged with Prevotella for 4 weeks. After inoculation, 16S rDNA sequencing was used to verify the colonization of Prevotella in the colon of mice. The IL-17A as well as IL-17A-expressing T cells was localized and quantified by an immunofluorescence assay (IFA) of colon sections. Th17 cells in the mesenteric lymph nodes of mice were counted by flow cytometry. Systemic immune response to Prevotella colonization was evaluated based on the serum levels of IL-6, TNF-α, IL-1β, IL-17A, IL-10, IL-4, IFN-γ, and IL-2. Th17-polarizing cytokines (IL-6, TNF-α, IL-1β, and IL-2) induced by Prevotella were evaluated by stimulation of bone marrow-derived dendritic cells (BMDCs). Results revealed that after inoculation, Prevotella successfully colonized the intestine of mice and induced the production and accumulation of colonic Th17 cells in the colon. Moreover, Prevotella elevated some of the Th17-related cytokines in the serum of mice. And Th17-polarizing cytokines (IL-6 and IL-1β) produced by BMDCs were mediated mainly through the interaction between Prevotella and Toll-like receptor 2 (TLR2). In conclusion, our data suggest that Prevotella induces the production of Th17 cells in the colon of mice, thus highlighting the potential role of Prevotella in training the intestinal immune system.

Evaluation of Surgical Site Infections After Change in Surgical Prophylaxis in VAD Patients

Background: In October 2013, the University of Maryland Medical Center established a formal antibiotic prophylaxis protocol for patients undergoing ventricular assist device (VAD) placement, replacing a previous system of various broad-spectrum antibiotic combinations typically for prolonged durations based on surgeon preference. This new protocol consisted of a standardized regimen of 72 hours of vancomycin and ceftriaxone after the procedure. The objective of this project was to evaluate the rate of surgical site infection (SSI) related to VAD placement to ensure that implementing the new protocol did not cause an increase in SSI rates. Methods: The study was a retrospective cohort study of patients who had undergone VAD placement before the protocol change (January 1, 2011, to October 1, 2013) and after the change (October 1, 2013, to November 15, 2015). The primary outcomes was the difference in SSI rate before and after the protocol change using CDC NHSN definitions. Pertinent data points of interest included reason for VAD placement, duration/type of antibiotics used, delayed sternal closure, SSI, characterization of infection (bloodstream, driveline, or pocket), organism identified on culture and mortality at 30 days and 1 year. SSI rates were assessed using the Fischer exact test, and descriptive statistics were used for other outcome variables. Results: In total, 75 patients were included before the protocol and 46 after the protocol change. Overall, 27% and 17% of patients were on therapeutic antibiotics prior to the VAD placement, respectively (P = 0.23). Also, 8 (6.6%) patients in the preintervention group had an SSI compared to 1 patient (0.8%) in the postintervention group (P = .15). Adherence to the protocol was suboptimal, with 27% of patients in the postintervention group receiving non–protocol-adherent antibiotics and 65% of patients receiving antibiotics >96 hours postoperatively. When evaluating the patients collectively, SSI rates were the same when antibiotics were discontinued <72 hours postoperatively versus when antibiotics were continued beyond 72 hours postoperatively or were not given at all postoperatively (3.1% vs 10.7% vs 0%; P = .24). SSI rates were also no different among patients who received cefazolin monotherapy (0%), vancomycin and ceftriaxone (2.7%), vancomycin and piperacillin tazobactam (2%), and other antibiotic combinations (7.7%) for surgical prophylaxis (P = 0.1). Conclusions: No change in SSI rates was noted after a protocol change narrowing the spectrum and duration of antibiotic prophylaxis was implemented. Evaluation of optimal surgical prophylaxis in this patient population is difficult due to low event rates and frequent therapeutic indications for antibiotics outside the standard prophylaxis. Despite these challenges, this study supports the safety of studying SSI prophylaxis reduction in the VAD population. Further studies are reasonable and warranted.Funding: NoneDisclosures: None

Pharmacotherapeutics for the New Coronavirus Pneumonia

The New Coronavirus Pneumonia (NCP, also named as COVID-19 by WHO on Feb 11 2020, is now causing a severe public health emergency in China since. The number of diagnosed cases is more than 40,000 until the submission of this manuscript. Coronavirus has caused several epidemic situations world widely, but the present contagious disease caused by 2019 new Coronavirus is unprecedentedly fulminating. The published cohorts of 2019 new Coronavirus (n-Cov) are single-center studies, or retrospective studies. We here share the therapeutic experiences of NCP treatment with literature review. Combination of Ribavirin and Interferon-α is recommended by the 5(th) edition National Health Commission's Regimen (Revised Edition) because of the effect on MERS (Middle East Respiratory Syndrome), and the effectiveness of Lopinavir/Ritonavir and Remdisivir needs to be confirmed by randomized controlled trial (RCT), given the situation of no specific antivirus drug on NCP is unavailable. Systemic glucocorticosteroid is recommended as a short term use (1~2 mg.kg(-1).d(-1), 3~5d ) by the 5(th) edition National Health Commission's Regimen (Revised Edition) yet RCTs are expected to confirm the effectiveness. Inappropriate application of antibiotics should be avoided, especially the combination of broad-spectrum antibiotics, for the NCP is not often complicated with bacterial infection.

Trends in Systemic Antibiotic Therapy of Endodontic Infections: a Survey among Dental Practitioners in Lithuania.

ABSTRACTObjectivesPrescription trends to certain antibiotic classes in Lithuania have been observed. Considering the potential contribution to antimicrobial resistance and the evidence of inappropriate prescriptions highlights, the periodical assessment of antibiotic consumption trends is required. The aim of this study was to assess prescription behaviours of Lithuanian general dental practitioners concerning the systemic antibiotic therapy of endodontic infections.Material and MethodsA sample of 198 Lithuanian dentists, registered on the database of the Lithuanian Dental Chamber, provided anonymous information about their clinical work by means of an online questionnaire.ResultsAmong the participants, antibiotics were prescribed in less than 20% of endodontic cases. Most common diagnosis for the prescription was symptomatic apical periodontitis with periostitis (90%) and apical abscesses with systemic involvement (54%). Amoxicillin and co-amoxiclav were the preferred choices for the antimicrobial therapy. The preference of clavulanic acid combination over simple usage of amoxicillin is increasing relative to the participants age (P = 0.016) and working experience (P = 0.008). Clindamycin is prescribed in cases of allergy to beta-lactams. Practitioners with less years of clinical activity were more likely to prescribe antibiotics for spreading infections, than their associates with more than 10 years of practice (P < 0.001).ConclusionsClinicians of higher age were found to be more likely to prescribe broad-spectrum antibiotic combinations compared to their younger associates. The majority of practitioners were aware of the clinical recommendations.

Treatment of late bacterial infections resulting from soft-tissue filler injections.

PurposeLate bacterial infections (LBIs) after esthetic facial augmentation using hyaluronic acid (HA) fillers are relatively rare yet severe complications that are difficult to treat. No adequate treatment standards have hitherto been formulated. We have bridged this gap by formulating a treatment scheme based on the principles of treating foreign-body implantation-related infections and treating bacterial growth in the form of biofilm. The objective of this study was to evaluate the efficacy of a comprehensive scheme for treating LBI complications after facial augmentation using cross-linked HA fillers.MethodsA total of 22 patients with LBI symptoms at a site of cross-linked HA injection underwent treatment and observation. The comprehensive treatment scheme formulated by Marusza and Netsvyetayeva (M&N scheme) comprised draining the lesion, dissolution of cross-linked HA with hyaluronidase, broad-spectrum antibiotic combination therapy, and use of probiotics. While 17 patients underwent the M&N scheme, the remaining five were treated with other schemes. Statistical analysis of the data was performed using Mann–Whitney U and χ2 nonparametric tests with SAS 9.4 software.ResultsAll 17 patients who underwent the M&N scheme experienced resolution of symptoms, with no recurrence of infection at the HA-injection sites.ConclusionTo treat LBI at a site of cross-linked HA administration, the principles applicable to infections resulting from implantation of a foreign body must be followed. The treatment period should be sufficiently long for complete resolution of symptoms. The efficacy of treatment is considered proven if 2 months have elapsed without recurrence since the symptoms resolved. The M&N scheme is recommended for use as the first therapeutic option for treating LBI related to soft-tissue fillers.

Analysis on treatment of extremely severe burn patients with severe inhalation injury in August 2nd Kunshan factory aluminum dust explosion accident

Objective: To summarize the measures and experience in diagnosis and treatment of extremely severe burn patients with severe inhalation injury in dust explosion accident. Methods: The medical records of 13 patients with extremely severe burn complicated with severe inhalation injury in August 2nd Kunshan factory aluminum dust explosion accident who were treated at the First Affiliated Hospital of Soochow University (hereinafter referred to as our hospital) on August 2nd, 2014, were retrospectively analyzed. All the patients were transferred to our hospital 3-8 hours after injury under the condition of inhalation of pure oxygen. Twelve patients underwent tracheotomy within 5 hours after admission, while 1 patient underwent tracheotomy before admission. All the patients were in ventilator-assisted respiration, with synchronized intermittent mandatory ventilation combined with positive end expiratory pressure. All the patients underwent thorax or limbs escharotomy on the second day after admission, so as to reduce the restrictive ventilatory dysfunction caused by the contraction of thorax eschar and the terminal circulation disorder caused by the contraction of limbs eschar. All the patients underwent electronic bronchoscopy within 48 hours after admission, airway secretion were cleared and airway lavage were carried out under electronic bronchoscope according to the patients' condition, and the sputum, lavage solution, pathological tissue were collected for microbiological culture. All the patients underwent chest X-ray examination on the second day after admission and reexamination as required. Patients were all treated with a combination of broad-spectrum antibiotics early after admission to control lung and systemic infection. One patient was treated with extracorporeal membrane oxygenation for acute respiratory distress syndrome 1 week after admission. Results: One patient suffered from cardiopulmonary arrest during tracheotomy, which recovered autonomous respiration and cardiac impulse after cardiopulmonary resuscitation. Three patients showed decreased pulse oxygen saturation (SpO(2)) within 48 hours after injury, and the SpO(2) returned to normal after sputum aspiration, scab removal and lavage under electronic bronchoscope. During the course of disease, bacteria were cultured from wound exudate of 7 patients, bacteremia occurred in 10 patients, and sputum microbiological culture results of 13 patients were positive. Eight of the 13 patients in this group survived, and 5 died. One patient died 19 days after injury, and 4 patients died 33-46 days after injury. The main cause of death was multiple organ dysfunction syndrome induced by severe septic shock eventually. Conclusions: For this batch of patients with extremely severe burn complicated with severe inhalation injury caused by dust explosion accident, the treatment and cure measures including early definite diagnosis and timely tracheotomy, the application of effective ventilation, the effective treatment of respiratory system complications, and rational use of antibiotics for the control of lung infection obtained quite good curative effect.

Impact of choice, timing, sequence and combination of broad-spectrum antibiotics on the outcome of allogeneic haematopoietic stem cell transplantation.

Recent data link the incidence of intestinal GvHD (iGvHD) after allogeneic haematopoietic stem cell transplantation (aSCT) to exposure with piperacillin-tazobactam or imipenem-cilastatin. To assess relevance of timing, duration, sequence and combination of antibiotic treatment in this setting, we applied a time-dependent model to our aSCT cohort. Patients from the prospective Cologne Cohort of Neutropenic Patients (CoCoNut) undergoing aSCT from January 2007 to April 2013 were included into a time-dependent multivariate Cox proportional hazards regression model with backward-stepwise selection. In 399 eligible patients, cumulative antibiotic exposure (hazard ratio (HR) 2.46; 95% confidence interval (95% CI) 1.59-3.81; P<0.001) and exposure to sequential treatment with penicillin derivatives and carbapenems (HR 6.22, 95% CI 1.27-30.31), but not to the individual classes, were associated with iGvHD at day 100. Glycopeptides were assessed as a risk factor (HR 3.73, 95% CI 1.51-9.19), but not considered independent, since their use was dependent on previous exposure to penicillin derivatives and carbapenems. Patients with iGvHD presented with increased non-relapse mortality at day 365 (HR 3.51; 95% CI 2.10-5.89; P<0.001). We identified sequential exposure to penicillin derivatives and carbapenems as well as overall exposure to antibiotics as independent risk factors for iGVHD. Confirmation of these findings in larger, prospective cohorts is necessary.

Translational Pharmacometric Evaluation of Typical Antibiotic Broad-Spectrum Combination Therapies Against Staphylococcus Aureus Exploiting In Vitro Information.

Broad‐spectrum antibiotic combination therapy is frequently applied due to increasing resistance development of infective pathogens. The objective of the present study was to evaluate two common empiric broad‐spectrum combination therapies consisting of either linezolid (LZD) or vancomycin (VAN) combined with meropenem (MER) against Staphylococcus aureus (S. aureus) as the most frequent causative pathogen of severe infections. A semimechanistic pharmacokinetic‐pharmacodynamic (PK‐PD) model mimicking a simplified bacterial life‐cycle of S. aureus was developed upon time‐kill curve data to describe the effects of LZD, VAN, and MER alone and in dual combinations. The PK‐PD model was successfully (i) evaluated with external data from two clinical S. aureus isolates and further drug combinations and (ii) challenged to predict common clinical PK‐PD indices and breakpoints. Finally, clinical trial simulations were performed that revealed that the combination of VAN‐MER might be favorable over LZD‐MER due to an unfavorable antagonistic interaction between LZD and MER.

Empiric antibiotic protocols for cancer patients with neutropenia: a single–center study of treatment efficacy and mortality in patients with bacteremia

BackgroundThere are several empiric antibiotic treatment options for febrile neutropenia, yet there is no universally-accepted initial protocol. We aimed to assess the performance of a protocol (piperacillin, gentamicin and cefazolin) introduced over 40 years ago and compare its coverage against bacteria isolated from blood of neutropenic patients with that of various commonly used antibiotic treatment protocols. MethodsAdults with neutropenia admitted between 2003 and 2012 to the hemato-oncologic departments and in whom blood cultures were taken on admission were included. Appropriateness of several common antibiotic protocols was assessed based on the susceptibility of the blood isolates. Crude mortality rates were computed by the susceptibility of bacteria isolated from patients' blood to the actual treatment given. ResultsIn total, 180 admissions of neutropenic patients (95 in patients who had fever above 38 °C) with positive blood cultures were analyzed. The actual antibiotic regimen prescribed was deemed appropriate in 82% of bacteremia episodes. The recommended institutional protocol was used in 62% of bacteremia episodes in neutropenic patients. This protocol would have been appropriate in 85% of all neutropenic bacteremia episodes and 89% of episodes in febrile neutropenia patients compared with piperacillin/tazobactam (79%, P = 0.13 and 76%, P = 0.002, respectively) and imipenem (93%, P = 0.004 and 92%, P = 0.74, respectively). Isolation of bacteria resistant to the actual antibiotic treatment given was associated with higher mortality at one week and at 30 days. ConclusionCommon current antibiotic regimens provide similar coverage among febrile neutropenic patients, whereas broad spectrum antibiotic combinations maximize coverage among neutropenic patients.

Eustachian Valve Endocarditis in an Intravenous Drug User

Case Description: We present the case of an intravenous drug user(IVDU) who presented with back pain. Initial Investigations and Management: His blood cultures demonstrated Staphylococcus aureus bacteraemia. He was diagnosed with a psoas abscess on CT scan, which was drained. He developed septic shock post operatively. CT chest demonstrated bilateral multifocal cavitating pneumonia with an inferior vena cava(IVC) thrombus for which patient had an IVC filter inserted. Transthoracic echocardiogram(TTE) demonstrated normal left and right ventricular function. The aortic and mitral valve were unremarkable, however there were vegetations visualised on the anterior(1.2 cm) and septal(1.0 cm) leaflets of the tricuspid valve with moderate regurgitation. Cardiothoracic surgical opinion was of conservative management at the time as there was no urgent indication for surgery. Despite a combination of broad spectrum antibiotics guided by the infectious disease specialists, our patient remained febrile with persistently positive blood cultures, elevated inflammatory markers and fluctuating levels of consciousness. Key Investigation: Transoesophageal echocardiogram(TOE) demonstrated anterior tricuspid valve vegetation, with aneurysm formation, localised perforation and eccentric severe regurgitation. The anteriorly directed tricuspid regurgitant jet had resulted in an infective seeding of the Eustachian valve, where a vegetation was visualised. The patient was transferred to ICU for further management of septic shock. He subsequently underwent tricuspid valve replacement, resection of the Eustachian valve, and completed the course of antibiotics, achieving a full recovery. The Eustachian valve vegetation was verified at surgery. Conclusion: This case demonstrates a rare form of endocarditis, with seeding of the Eustachian valve from a tricuspid valve jet lesion.

Prevention of Propionibacterium acnes biofilm formation in prosthetic infections in vitro

The role of Propionibacterium acnes in shoulder arthroplasty and broadly in orthopedic prosthetic infections has historically been underestimated, with biofilm formation identified as a key virulence factor attributed to invasive isolates. With an often indolent clinical course, P acnes infection can be difficult to detect and treat. This study investigates absorbable cements loaded with a broad-spectrum antibiotic combination as an effective preventive strategy to combat P acnes biofilms. P acnes biofilm formation on an unloaded synthetic calcium sulfate (CaSO4) bone void filler cement bead was evaluated by scanning electron microscopy over a period of 14 days. Beads loaded with tobramycin alone or vancomycin alone (as comparative controls) and beads loaded with a vancomycin-tobramycin dual treatment were assessed for their ability to eradicate planktonic P acnes, prevent biofilm formation, and eradicate preformed biofilms using a combination of viable-cell counts, confocal microscopy, and scanning electron microscopy. P acnes surface colonization and biofilm formation on unloaded CaSO4 beads was slow. Beads loaded with antibiotics were able to kill planktonic cultures of 106 colony-forming units/mL, prevent bacterial colonization, and significantly reduce biofilm formation over periods of weeks. Complete eradication of established biofilms was achieved with a contact time of 1 week. This study demonstrates that antibiotic-loaded CaSO4 beads may represent an effective antibacterial and antibiofilm strategy to combat prosthetic infections in which P acnes is involved.

Simultaneous determination and stability studies of linezolid, meropenem and vancomycin in bacterial growth medium by high-performance liquid chromatography.

For pharmacokinetic/pharmacodynamic (PK/PD) assessment of antibiotics combinations in in vitro infection models, accurate and precise quantification of drug concentrations in bacterial growth medium is crucial for derivation of valid PK/PD relationships. We aimed to (i) develop a high-performance liquid chromatography (HPLC) assay to simultaneously quantify linezolid (LZD), vancomycin (VAN) and meropenem (MER), as typical components of broad-spectrum antibiotic combination therapy, in bacterial growth medium cation-adjusted Mueller-Hinton broth (CaMHB) and (ii) determine the stability profiles of LZD, VAN and MER under conditions in in vitro infection models. To separate sample matrix components, the final method comprised the pretreatment of 100μL sample with 400μL methanol, the evaporation of supernatant and its reconstitution in water. A low sample volume of 2μL processed sample was injected onto an Accucore C-18 column (2.6μm, 100×2.1mm) coupled to a Dionex Ultimate 3000 HPLC+ system. UV detection at 251, 240 and 302nm allowed quantification limits of 0.5, 2 and 0.5μg/mL for LZD, VAN and MER, respectively. The assay was successfully validated according to the relevant EMA guideline. The rapid method (14min) was successfully applied to quantify significant degradation of LZD, VAN and MER in in vitro infection models: LZD was stable, VAN degraded to 90.6% and MER to 62.9% within 24h compared to t=0 in CaMHB at 37°C, which should be considered when deriving PK/PD relationships in in vitro infection models. Inclusion of further antibiotics into the flexible gradient-based HPLC assay seems promising.

High Frequency of Polymicrobial Infections After Surgical Resection of Malignant Bone and Soft Tissue Tumors: A Retrospective Cohort Study.

IntroductionSurgical resection of a malignant bone tumor (BT) or soft tissue tumor (STT), with or without prosthetic replacement, carries a high risk of developing postoperative infections. There is limited knowledge on the bacteriological spectrum of these postsurgical infections that necessitate empirical antibiotic therapy. The aim of this study was to analyze the incidence and microbiological features of site infections following BT or STT resection.MethodsIn this retrospective mono-center study, we analyzed the surgical and bacteriological data of all consecutive patients who developed an infection after surgical resection of a BT or STT between January 2010 and April 2014.ResultsSeventy-two consecutive patients who developed an infection on the site of surgical treatment for a BT (n = 42) or SST (n = 30) were included. Polymicrobism was frequently observed, more often associated with STTs (93%) than BTs (71%; P = 0.03). Gram-negative bacteria were more frequently isolated in STTs (55%) than in BTs (26%; P = 0.01) and non-prosthesis-associated infections (54%) than prosthesis-associated infections (29%; P = 0.04), whereas staphylococci were more frequently found in BTs (76%) than in STTs (52%; P = 0.03). Overall, we found gram negatives in 82% of early acute infections, 11% of chronic infections and 7% of late acute infections (P < 0.01).ConclusionPostoperative infections in patients after surgical resection of BTs or STTs were often polymicrobial, especially following STTs. Causative bacteria were often gram negatives in STTs and non-prosthesis-associated infections, whereas staphylococci were predominant in BTs. Based on these findings, we recommend antibiotic coverage of both gram-positive and -negative bacteria with a combination of broad-spectrum antibiotics in STTs and antistaphylococcal antibiotics as first-line therapy in infections following BT surgery.