Resistant Gram-positive Organisms Research Articles

Evaluation of different linezolid susceptibility testing methods and detection of linezolid resistance gene (cfr) in staphylococcal isolates

Linezolid is an effective oxazolidinone antibiotic against multi resistant Gram-positive organisms. Linezolid resistance is an emerging problem and some controversy exists about the reliability of different phenotypic methods of linezolid susceptibility testing. Fifty isolates each of methicillin resistant S. aureus (MRSA) and Staphylococcus haemolyticus were tested for linezolid susceptibility using Kirby-Bauer disc diffusion, E-test, automated system VITEK2, Broth micro-dilution (reference method) and PCR for the cfr gene. Six resistant isolates were identified, three each in MRSA and S. haemolyticus, all carrying the cfr gene. E-test and VITEK2 were found to be more accurate than disc diffusion test.

Microbiological Profile of Fracture Related Infection at a UK Major Trauma Centre.

Fracture Related Infection (FRI) represents one of the biggest challenges for Trauma and Orthopaedic surgery. A better understanding of the microbiological profile should assist with decision-making and optimising outcomes. Our primary aim was to report on the microbiological profile of FRI cases treated over a six-year period at one of Europe's busiest trauma centres. Secondarily, we sought to correlate our findings with existing anti-microbiological protocols and report on diagnostic techniques employed in our practice. All adult cases of FRI treated in our institution between 2016 and 2021 were identified, retrospectively. We recorded patient demographics, diagnostic strategies, causative organisms and antibiotic susceptibilities. There were 330 infection episodes in 294 patients. A total of 463 potentially pathogenic organisms (78 different species) were identified from cultures, of which 57.2% were gram-positive and 39.7% gram-negative. Polymicrobial cultures were found in 33.6% of cases and no causative organism was found in 17.5%. The most prevalent organisms were Staphylococcus aureus (24.4%), coagulase-negative Staphylococci (14%), Pseudomonas aeruginosa (8.2%), Enterobacter species (7.8%) and Escherichia coli (6.9%). Resistant gram-positive organisms (methicillin resistant Staphylococcus aureus or vancomycin-resistant Enterococci) were implicated in 3.3% of infection episodes and resistant gram-negatives (extended-spectrum beta-lactamase, ampC or carbapenemase-producing bacteria) in 13.6%. The organisms cultured in 96.3% of infection episodes would have been covered by our empirical systemic antibiotic choice of teicoplanin and meropenem. To our knowledge, this is the largest reported single-centre cohort of FRIs from a major trauma centre. Our results demonstrate patterns in microbiological profiles that should serve to inform the decision-making process regarding antibiotic choices for both prophylaxis and treatment.

Identification of 5-(Aryl/Heteroaryl)amino-4-quinolones as Potent Membrane-Disrupting Agents to Combat Antibiotic-Resistant Gram-Positive Bacteria.

Nosocomial infections caused by resistant Gram-positive organisms are on the rise, presumably due to a combination of factors including prolonged hospital exposure, increased use of invasive procedures, and pervasive antibiotic therapy. Although antibiotic stewardship and infection control measures are helpful, newer agents against multidrug-resistant (MDR) Gram-positive bacteria are urgently needed. Here, we describe our efforts that led to the identification of 5-amino-4-quinolone 111 with exceptionally potent Gram-positive activity with minimum inhibitory concentrations (MICs) ≤0.06 μg/mL against numerous clinical isolates. Preliminary mechanism of action and resistance studies demonstrate that the 5-amino-4-quinolones are bacteriostatic, do not select for resistance, and selectively disrupt bacterial membranes. While the precise molecular mechanism has not been elucidated, the lead compound is nontoxic displaying a therapeutic index greater than 500, is devoid of hemolytic activity, and has attractive physicochemical properties (clog P = 3.8, molecular weight (MW) = 441) that warrant further investigation of this promising antibacterial scaffold for the treatment of Gram-positive infections.

Multicenter evaluation of contamination of the healthcare environment near patients with Candida auris skin colonization

Background:Candida auris is an emerging multidrug-resistant yeast that is transmitted in healthcare facilities and is associated with substantial morbidity and mortality. Environmental contamination is suspected to play an important role in transmission but additional information is needed to inform environmental cleaning recommendations to prevent spread. Methods: We conducted a multiregional (Chicago, IL; Irvine, CA) prospective study of environmental contamination associated with C. auris colonization of patients and residents of 4 long-term care facilities and 1 acute-care hospital. Participants were identified by screening or clinical cultures. Samples were collected from participants’ body sites (eg, nares, axillae, inguinal creases, palms and fingertips, and perianal skin) and their environment before room cleaning. Daily room cleaning and disinfection by facility environmental service workers was followed by targeted cleaning of high-touch surfaces by research staff using hydrogen peroxide wipes (see EPA-approved product for C. auris, List P). Samples were collected immediately after cleaning from high-touch surfaces and repeated at 4-hour intervals up to 12 hours. A pilot phase (n = 12 patients) was conducted to identify the value of testing specific high-touch surfaces to assess environmental contamination. High-yield surfaces were included in the full evaluation phase (n = 20 patients) (Fig. 1). Samples were submitted for semiquantitative culture of C. auris and other multidrug-resistant organisms (MDROs) including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum β-lactamase–producing Enterobacterales (ESBLs), and carbapenem-resistant Enterobacterales (CRE). Times to room surface contamination with C. auris and other MDROs after effective cleaning were analyzed. Results:Candida auris colonization was most frequently detected in the nares (72%) and palms and fingertips (72%). Cocolonization of body sites with other MDROs was common (Fig. 2). Surfaces located close to the patient were commonly recontaminated with C. auris by 4 hours after cleaning, including the overbed table (24%), bed handrail (24%), and TV remote or call button (19%). Environmental cocontamination was more common with resistant gram-positive organisms (MRSA and, VRE) than resistant gram-negative organisms (Fig. 3). C. auris was rarely detected on surfaces located outside a patient’s room (1 of 120 swabs; <1%). Conclusions: Environmental surfaces near C. auris–colonized patients were rapidly recontaminated after cleaning and disinfection. Cocolonization of skin and environment with other MDROs was common, with resistant gram-positive organisms predominating over gram-negative organisms on environmental surfaces. Limitations include lack of organism sequencing or typing to confirm environmental contamination was from the room resident. Rapid recontamination of environmental surfaces after manual cleaning and disinfection suggests that alternate mitigation strategies should be evaluated.Funding: NoneDisclosures: None

Correction of thrombocytopenia caused by linezolid with scheduled sequential tedizolid use in patients with vertebral osteomyelitis by antibiotic resistant Gram-positive organisms

IntroductionBecause of thrombocytopenia, linezolid treatment tends to be stopped before the completion of therapy for complicated infections that require prolonged antimicrobial administration. In contrast, tedizolid shows a favorable hematologic profile. The primary end-point of this study was to evaluate the efficacy of switching treatment to tedizolid in patients who developed thrombocytopenia during linezolid therapy. MethodsThis retrospective study was conducted in patients with vertebral osteomyelitis (VO) caused by antibiotic-resistant Gram-positive bacteria. Treatment failure was defined as the reappearance of infection signs within 2 weeks after stopping tedizolid and discontinuation of tedizolid because of continued thrombocytopenia or other adverse effects. ResultsEight patients with native VO (n = 3) and postoperative VO (n = 5) were included in the study. The causative organisms were MRSA in all patients except one. Platelet counts decreased from 35.2 ± 11.5 × 104/mm3 to 17.8 ± 6.2 × 104/mm3 during linezolid therapy and improved without washout period in all patients after switching to tedizolid on days 5–7 (28.6 ± 4.9 × 104/mm3, p = 0.002). Tedizolid therapy was completed and treatment failure was not observed in any patient. The duration of treatment was 20.0 ± 11.2 days for linezolid and 30.3 ± 9.5 days for tedizolid (total, 50.3 ± 10.7 days). One patient died because of underlying disease, and there was no recurrence in the remaining 7 patients (median follow-up 501 days). ConclusionsSwitching therapy to tedizolid improved thrombocytopenia that occurred during linezolid therapy, and it enabled the completion of therapy for VO patients.

S2874 A Tale of Two Cultures: A Case of a Recurrence of Multi-Drug-Resistant Spontaneous Bacterial Peritonitis

Introduction: Spontaneous bacterial Peritonitis (SBP) is an ascitic fluid infection that is potentially life threatening in cirrhotic patients. A diagnosis is confirmed with a polymorphonuclear leukocyte (PMN) count of ≥ 250 and a positive culture in sampled ascites. Current guidelines recommend SBP screening in all admitted cirrhotic patients, and third generation cephalosporins are commonly used in prophylaxis and treatment. With widespread use of antibiotics, a rise in bacterial resistance has been noted. Here we present a case of two resistant SBP infections developing in a patient over two months. Case Description/Methods: A 52-year-old male with a history of chronic lyme disease requiring multiple antibiotic infusions and recently diagnosed alcoholic hepatitis presented with abdominal pain. Blood workup revealed a total bilirubin of 34.2 mg/dL, alanine transaminase of 120 U/L, and aspartate transaminase of 244 U/L. Paracentesis was performed after vancomycin, cefepime and zosyn were administered at an outside hospital prior to transfer. The ascitic fluid PMN count was 24,492. Ceftriaxone was empirically started, and cultures then identified Escherichia Coli resistant to amoxicillin-clavulaunate, ampicillin-sulbactam, cefazolin, cefotaxime, and ceftazidime. Ceftriaxone was switched to ertapenem and ultimately levofloxacin. The patient improved clinically and serial paracenteses showed a downtrend in PMNs and no further culture positivity. The patient then underwent an outpatient paracentesis 12 days later revealing a PMN count of 1,972. He was admitted, and ertapenem was started empirically as per prior hospitalization. Paracentesis was repeated 2 days later yielding a PMN count of 15,853 and the culture grew Enterococcus facieum resistant to ampicillin and vancomycin. Ertapenem was continued during admission and the patient was discharged with linezolid to complete the antibiotic course. Discussion: SBP is a potentially life threatening infection. Signs and symptoms may be nonspecific. While 3rd generation cephalosporins are commonly used for therapy and prophylaxis, our case sheds light on some of the therapeutic challenges in treating SBP effectively, particularly with regards to potential selection for drug-resistant gram-positive organisms. As resistant organisms and gram-positive organisms are encountered more frequently in SBP, it is imperative that antibiotics are selected and used appropriately.

A retrospective analysis of cases of Spontaneous Bacterial Peritonitis in cirrhosis patients.

Spontaneous Bacterial Peritonitis (SBP) is an infection in patients with cirrhosis and carries significant mortality. The management of SBP is evolving with the rise of multidrug resistant organisms. Our aim was to perform a retrospective analysis to determine if identification of bacteria in culture could aid in prognosis and provide information regarding optimal treatment. We analyzed our 10-year experience of SBP in a single academic center (Northwestern Memorial Hospital). We obtained information regarding SBP prophylaxis, culture data and resistance patterns of bacteria, choice/duration of inpatient antibiotics, and key laboratory measurements and determined outcomes including mortality, hospital duration, and ICU stay. Patients with SBP had a 17.8% mortality and had culture positive SBP 34.4% of the time. Antimicrobial resistance was seen in 21.3% of cases and trended towards worsening mortality, with worsened mortality associated with first line use of piperacillin-tazobactam (p = 0.0001). Patients on SBP prophylaxis who developed SBP had improved mortality (p<0.0001) unless there was a positive culture, in which case patients had worsened mortality (p = 0.019). Patient with a higher PMN counts after repeat paracentesis had higher mortality (p = 0.02). Our results show that SBP continues to be a morbid and deadly condition and identification of an organism is key in treatment. The standard initial antibiotic for SBP may need to be modified to reflect emerging resistant pathogens and gram-positive organisms. Further, antibiotic prophylaxis should be utilized only in select cases to prevent development of resistance.

Clinical use of linezolid in periprosthetic joint infections - a systematic review.

Introduction: The most common causative organism in periprosthetic joint infections (PJIs) is Gram-positive bacteria that are increasingly drug resistant. In these cases the use of linezolid may be warranted. However, there are conflicting reports regarding its role in antibiotic treatment of PJIs. The aim of this review is to gather and analyze clinical results and treatment details on linezolid in patients with PJIs. Methods: In August 2019, a comprehensive literature search using MEDLINE (Pubmed and Ovid) and Cochrane Library was performed. A total of 504 records were screened, and a total of 16 studies including 372 patients treated with linezolid for a PJI were included in this review based on the PRISMA criteria and after quality analysis using the MINOR score and Newcastle–Ottawa scale, as well as assessing level of evidence. Pooling analysis as well as descriptive analysis was performed. Results: Based on the results from the studies included, infection control was achieved in 80 % (range 30 %–100 %) of patients after a mean follow-up period of 25 (range 2–66) months. The mean duration of treatment was 58 d intravenous and orally at a median dose of 600 mg bis in die (b.i.d.) (range 400–900 b.i.d.). A combination therapy with rifampicin was used in 53 % of patients. MRSA (methicillin-resistant Staphylococcus aureus) infections were present in 29 % and resistant CoNS (coagulase-negative Staphylococcus) in 46 %. Adverse effects occurred in 33 % of cases, mostly anemia, thrombocytopenia and gastrointestinal complaints leading to treatment discontinuation in 9 %. However, great heterogeneity was found with respect to surgical treatment, diagnosis of infection and indication for linezolid. Discussion: Linezolid is an appropriate option for treatment of resistant Gram-positive organisms in PJIs. Most commonly 600 mg b.i.d. is used, and a combination with rifampicin appears feasible although one must consider individual increases in doses in these cases. However, adverse effects are common and there are limited data for long-term use and optimal antibiotic combinations or individual doses.

2532. Identifying Educational Needs and Improving Provider Knowledge Regarding the Management of Febrile Neutropenia

BackgroundIn a retrospective chart review of 211 first episodes of febrile neutropenia (FN) in in-patients with acute myelogenous leukemia evaluating rates of appropriate vs. inappropriate management, we identified frequent noncompliance with national guidelines for the management of FN. We utilized these data to develop an educational intervention targeting front-line providers.MethodsBased on findings from our chart review, we developed and implemented an interactive, case-based didactic session for advanced practice providers (APPs) and medical students/residents rotating on hematology, targeting inappropriate antibiotic use. Pretest questions were embedded into the lecture, preceding content related to each learning objective. Lecture material included content from national guidelines, literature addressing misconceptions (e.g., vancomycin usage for persistent fever), and data from our institutional antibiogram (Figure 1). A post-test was given directly after the lecture to evaluate knowledge gained.ResultsFive inappropriate behaviors were identified (Figure 2): (1) changing empiric therapy despite clinical stability, (2) misunderstanding piperacillin/tazobactam’s spectrum of activity, (3) inappropriate initiation of antibiotics active against resistant Gram-positive organisms; (4) failure to de-escalate therapy at 72 hours and (5) failure to add Gram-positive coverage when using aztreonam. Lectures were provided to 13 APPs and 17 medical students/residents over 6 sessions. An improvement in knowledge was noted for most learning objectives except for the third, for which misconceptions remained, especially regarding need for vancomycin in the setting of mucositis (Figures 3 and 4). Higher baseline knowledge was noted for medical students/residents than APPs. 93% of learners rated the lecture very/extremely helpful. Learners recommended future content focus on antifungal therapy.ConclusionWe utilized local practice data to develop educational content for front-line providers. We will convert this lecture into a video-format to be incorporated into hematology rotations to reinforce key concepts. A prospective cohort study to evaluate the impact on prescribing behavior is underway. Disclosures All authors: No reported disclosures.

The impact of a multimodal approach to vancomycin discontinuation in hematopoietic stem cell transplant recipients (HSCT) with febrile neutropenia (FN).

Current guidelines recommend adding vancomycin to empiric treatment of FN in patients who meet specific criteria. After 48hours, the guidelines recommend discontinuing vancomycin if resistant Gram-positive organisms are not identified. Based on these recommendations, a vancomycin stewardship team defined criteria for discontinuation of vancomycin at 48hours and increased surveillance of vancomycin usage through a multimodal approach. The purpose of this retrospective analysis is to assess the impact of this multimodal approach on the discontinuation of empiric vancomycin at 48hours in FN. This retrospective analysis included a pre- and post-intervention cohort of 200 HSCT recipients with FN from 2015 to 2018. Criteria for continued vancomycin use beyond 48hours included culture-documented resistant Gram-positive infection, positive Methicillin-Resistant Saureus (MRSA) nasal swab with evidence of pneumonia, or hemodynamic instability with concern for sepsis. The following patient characteristics were collected: previous MRSA infection, MRSA nasal swab collection and results, culture results, duration of vancomycin use, rationale for continuation of vancomycin beyond 48hours, and re-initiation of vancomycin. In the post-intervention cohort, vancomycin discontinuation at 48hours increased from 31% (95% CI 21.94-40.05) to 70% (95% CI 61.02-78.97; P<0.0001). An additional 23% of vancomycin orders were discontinued at 72hours. Off criteria vancomycin use decreased from 33% in pre to 1% in the post-implementation cohort. Establishing define criteria for vancomycin use in FN patients with a multimodal approach of physicians from hematology and infectious diseases, clinical pharmacists and the antibiotic stewardship team significantly improved vancomycin discontinuation.

265. Identification of Solid-Organ Transplant Antimicrobial Stewardship Opportunities in Pediatric Liver Transplant Patients

BackgroundThrough the prospective audit with feedback program, postoperative antimicrobial use for pediatric liver transplant was observed to extend beyond the recommended 24 hours for surgical site infection (SSI) prophylaxis. Bacterial infections in the immediate post-transplant period represent significant risk in pediatric liver-transplant recipients, including SSI. We describe our posttransplant antimicrobial (PTA) utilization in the largest pediatric liver transplant center to determine opportunities for the antimicrobial stewardship program (ASP).MethodsAll children who underwent a liver transplant between January 1, 2017 and September 30, 2017 at our institution were included. Antimicrobials initiated within 14 days posttransplant were captured, presence of fever within 14 days, positive microbiologic data within 30 days, and massive transfusion protocol (MTP) status were collected. The primary endpoint was duration of PTA. Clinical factors associated with PTA use >48 hours were evaluated.ResultsThirty-eight children underwent a liver transplant during the study period and 29 (76%) received a broad-spectrum Gram-negative (GN) antibiotic for > 48 hours posttransplant. Half of the patients received vancomycin and 15 (40%) received an antifungal posttransplant. Fever occurred in 21 (55%) of patients with a median onset of 1 day; 3 (8%) patients had a culture-proven posttransplant bacterial infection, with no resistant Gram-positive organisms identified. Eight patients (21%) met MTP and received PTA for ≥7 days and none had a positive bacterial culture. No differences were detected in fever or culture proven posttransplant infection between patients who received ≤48 hours of GN antibiotics compared with those who received >48 hours.ConclusionThe majority of children received PTA beyond 48 hours which was not attributable to prolonged posttransplant fevers or positive cultures. We identified ASP opportunities, including limiting GN antibiotics to 48 hours posttransplant, eliminating empiric vancomycin, restricting antifungals to MTP only, and limiting MTP PTA to 5 days.Disclosures All authors: No reported disclosures.

Enhancing Antibiotic Stewardship Team (AST) Efforts in Decreasing Inappropriate Vancomycin Usage in Neutropenic Fever (NF) Patients through Unit Based Pharmacist Intervention

BackgroundThe Infectious Diseases Society of America and the National Comprehensive Cancer Network guidelines recommend adding vancomycin to the empiric treatment of NF in patients meeting specific criteria. After 48 hours, the guidelines recommend discontinuing vancomycin if resistant Gram-positive organisms are not identified. An analysis of vancomycin use for NF at our institution revealed 35% of patients had vancomycin discontinued appropriately at 48 hours. Based on these results, a vancomycin stewardship team defined criteria for continuation of vancomycin past 48 hours and increased surveillance of vancomycin usage through AST oversight. The objective of this study is to assess the incidence of vancomycin discontinuation at 48 hours with the new criteria of use and the addition of pharmacist led stewardship.MethodsThis study included NF patients who were treated with an antipseudomonal β-lactam and vancomycin from January to April 2017. Criteria for vancomycin continuation beyond 48 hours included culture-documented Gram-positive infection, positive Methicillin Resistant S.aureus (MRSA) nasal swab with evidence of pneumonia, or hemodynamic instability due to septic shock. Patients who received aztreonam, or a single dose of vancomycin were excluded. Patient characteristics, previous MRSA infection, MRSA nasal swab collection and results, culture results, fever status, duration of vancomycin, rationale for continuation of vancomycin past 48 hours, re-initiation of vancomycin, and AST recommendations were collected.ResultsSixty-nine patients with 73 admissions were initiated on vancomycin for NF during the study period. Vancomycin was appropriately discontinued in 63% (46/73) compared with 35% (19/54) previously. An additional 8% (6/73) was discontinued between 48 and 72 hours, and 20% (15/73) was continued past 72 hours inappropriately. The most common reasons for continuation was lack of neutrophil recovery (5) and cellulitis (4). AST recommended discontinuation on 5 patients, all of which were accepted.ConclusionEstablishing criteria for vancomycin use along with pharmacist led antibiotic surveillance, AST, and provider education improved the use of vancomycin with the discontinuation rate increasing from 35% to 63%.(P = 0.002)Disclosures All authors: No reported disclosures.

New Inhaled Antimicrobial Formulations for Use in the Cystic Fibrosis Patient Population.

To review the current literature on inhaled antibiotic therapies currently in clinical trials for cystic fibrosis (CF) patients. A literature search was performed using PubMed (1975 to September 2015), International Pharmaceutical Abstracts (1970 to September 2015), and MEDLINE (1946 to September 2015) to identify studies for inclusion. The following search terms were used: cystic fibrosis, inhaled amikacin, inhaled liposomal amikacin, inhaled vancomycin, and/or inhaled levofloxacin. All English-language phase II to III studies evaluating efficacy and/or safety, case reports, and retrospective studies of inhaled amikacin, inhaled vancomycin, and inhaled levofloxacin in CF patients were included. Currently available inhaled antibiotics, tobramycin and aztreonam, have demonstrated improvement in respiratory function of CF patients. Newer agents have shown potentially similar efficacy, with improvement in ease of use. Limited data suggest that inhaled liposomal amikacin and levofloxacin are both noninferior to tobramycin in terms of improvements in respiratory function. Inhaled levofloxacin has a lower rate of hospitalizations secondary to respiratory exacerbations and a reduction in the Pseudomonas aeruginosa sputum density compared with inhaled tobramycin. Inhaled vancomycin use has been documented in case reports and 2 small retrospective eradication trials, although data are limited to support its use. The horizon of inhaled antibiotic choices for CF patients is promising. The introduction of different drug classes and formulations to treat resistant Gram-negative and Gram-positive organisms increases the number of options for patients for both eradication and treatment of chronic colonization.

A Comparative Study of Piperacillin-Tazobactam With and Without Vancomycin as Empirical Therapy for Febrile Neutropenic Patients With Solid Tumor Malignancies.

BackgroundThe objective of this study was to evaluate the outcomes, mortality and toxicity associated with piperacillin-tazobactam (PT) and the addition of vancomycin (VM) to the empirical treatment of febrile neutropenic cancer patients.MethodA retrospective study on adult febrile neutropenic patients who were admitted between September 2008 and May 2013 with solid tumor malignancies was conducted at King Fahad Specialist Hospital Dammam, Saudi Arabia.ResultsOut of 86 febrile neutropenic patients, 60 patients were treated with PT group and 26 patients were with PT + VM group. The two groups were comparable in terms of outcome, mortality, nephrotoxicities and hepatotoxicities. The median duration of neutropenia in PT treatment group was 4 days (range 1 - 10) in the female and 7 days (range 1 - 13) in males while in PT + VM 6 days (range 1 - 5) in female and 7.5 days (range 1 - 6) in male with significance P = 0.007. There was no significant difference in terms of duration of fever and length of stay between the two treatment groups. There were no deaths reported during treatment in both groups. In PT, the microbial eradication was 27/40 (67.5%) patients (14/27 (51.9%) of female and 13/27 (48.1%) of male)), whereas it was 13/40 (32.5%) patients (9/13 (69.2%) of female and 4/13 (30.8%) of male)) in PT + VM group. Overall, there was no significant difference in terms of microbiological eradication between the two groups (OR: 1.22; 95% CI: 0.486 - 3.072; X2 stat: 0.182; P = 0.67). Response to therapy in clinically defined infections was higher 16/23 (69.56%) in PT treatment group than 7/23 (30.44%) in PT + VM group. But there was no significant difference between the two treatment groups in terms of clinically defined infections (OR: 1.013; 95% CI: 0.359 - 2.862; X2 stat: 0.001; P = 0.98). There was no significant difference in renal and liver functions between the two groups in terms of serum creatinine level and clearance, alkaline phosphate and alanine tranferase and gama glutamyl tranferase. The most commonly isolated organisms were Escherichais coli (eighteen isolates), Staphylococcus aureus (seven isolates), Streptococcus spp (six isolates) and Klebsiella pneumonia (four isolates). The overall success rate was similar in both treatment arms and treatment was well tolerated, with no severe adverse reactions reported.ConclusionAlthough the addition of VM might provide an additional value for coverage of gram-positive pathogens. This study demonstrates that there was no significant difference in terms of response rate in both treatment groups, which could be due to the low local methicillin-resistant Staphylococcus aureus (MRSA) rates and other resistant gram-positive organisms at our institution, stressing the importance of local antibiograms in developing empirical neutropenic fever protocols.

Evidence-based protocol for prophylactic antibiotics in open fractures: improved antibiotic stewardship with no increase in infection rates.

Evidence-based guidelines for prophylactic antibiotic use in open fractures recommend short-course, narrow-spectrum antibiotics for Gustilo Grade I or II open fractures and broader gram-negative coverage for Grade III open fractures. No studies to date have assessed the impact of these guidelines on infection rates in open fractures. Infection rates before and after the new protocol implementation were examined. A new protocol was implemented including antibiotic prophylaxis based on grade of open fracture: Grade I/II fractures, cefazolin (clindamycin if allergy); Grade III fractures, ceftriaxone (clindamycin and aztreonam if allergy) for 48 hours. Aminoglycosides, vancomycin, and penicillin were removed from the protocol. Data for 174 femur and tibia/fibula open fractures (101 preprotocol and 73 postprotocol) were analyzed. Patients who were moribund or managed at another institution for greater than 24 hours were excluded. The National Healthcare Safety Network risk index was used to provide risk adjustment. No significant differences in the study cohorts (preprotocol and postprotocol) were identified for demographics (age, 37.2 [14.8] years vs. 40.0 [17.9] years; male, 71.3% vs. 79.5%) or mechanism of injury (motor vehicle crash, 67.3% vs. 64.4%; other blunt, 28.7% vs. 32.9%; penetrating, 4.0% vs. 2.8%). After protocol implementation, the use of aminoglycoside and glycopeptide antibiotics was significantly reduced (53.5% vs. 16.4%, p = 0.0001). The skin and soft tissue infection rate per fracture event was 20.8% before and 24.7% after protocol implementation (p = 0.58). There was no statistically significant change after stratification for fracture grade, National Healthcare Safety Network risk index, or fracture site. The rate per fracture event of resistant gram-positive and gram-negative organisms (15.8% vs. 17.8%, p = 0.84) and methicillin-resistant Staphylococcus aureus (2.0% vs. 4.1%, p = 0.65) was not different. Implementation of an evidence-based protocol for open fracture antibiotic prophylaxis resulted in significantly decreased use of aminoglycoside and glycopeptide antibiotics with no increase in skin and soft tissue infection rates. Therapeutic study, level IV.

Ceftaroline activity tested against bacterial isolates from pediatric patients: results from the assessing worldwide antimicrobial resistance and evaluation program for the United States (2011-2012).

Ceftaroline, the active form of ceftaroline fosamil, is a cephalosporin with broad-spectrum bactericidal activity against resistant Gram-positive organisms, including methicillin-resistant Staphylococcus aureus, ceftriaxone-resistant Streptococcus pneumoniae and many Enterobacteriaceae species. Ceftaroline fosamil is approved in the United States for treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia in adults. A total of 5291 consecutive unique pediatric patient strains of clinical significance were collected from 157 US medical centers. The isolates were identified locally and forwarded to a central monitoring laboratory for reference antimicrobial susceptibility testing. S. pneumoniae isolates from the 2011 to 2012 respiratory season were serotyped. Susceptibility results were analyzed according to patient age as follows: ≤ 1 years old (yo; 1857 strains); 2-5 (1342); 6-12 (1281) and 13-17 (811). Methicillin-resistant Staphylococcus aureus rates were slightly lower in isolates from patients 13-17 yo (39.9%) compared with other age groups (48.2-51.5%), and ceftaroline was consistently active against S. aureus isolates from all 4 age groups [minimal inhibitory concentration (MIC50/90): 0.25-05/1 μg/mL; 99.8-100.0% susceptible]. Overall, 99.8% of methicillin-resistant Staphylococcus aureus were ceftaroline susceptible (MIC50/90: 0.5/1 μg/mL). All S. pneumoniae strains (1178) were ceftaroline susceptible (MIC50/90: ≤ 0.015/0.12 μg/mL), whereas ceftriaxone susceptibility varied from only 84.8 (≤ 1 yo) to 89.7% (13-17 yo). 19A was the most frequent serotype identified among S. pneumoniae and these isolates exhibited low susceptibility to ceftriaxone (42.4%) and most other antimicrobials tested. The highest ceftaroline MIC among Haemophilus influenzae (587 strains) was 0.12 μg/mL (100.0% susceptible), and β-lactamase production rates varied from 24.2 (13-17 yo) to 30.1% (6-12 yo); 27.9% overall. Ceftaroline was also active against β-hemolytic streptococci (556 strains, highest MIC, 0.06 μg/mL). Extended-spectrum β-lactamase (ESBL)-phenotype rates among Escherichia coli/Klebsiella spp. were 6.0/5.1, 11.0/11.5, 5.1/8.3 and 11.4/14.7% for the ≤ 1, 2-5, 6-12 and 13-17 yo age groups, respectively. Ceftaroline exhibited good activity against non-ESBL phenotype strains of E. coli and Klebsiella spp. (MIC90: 0.25 μg/mL for both organisms), but had limited activity against ESBL-producing strains. Ceftaroline demonstrated potent in vitro activity when tested against S. aureus, S. pneumoniae, H. influenzae, β-hemolytic streptococci and non-ESBL-phenotype E. coli and Klebsiella spp. strains isolated from pediatric patients, independent of patient age.

Ceftaroline activity against bacterial organisms isolated from acute bacterial skin and skin structure infections in United States medical centers (2009–2011)

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a new cephalosporin with bactericidal activity against resistant Gram-positive organisms including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant strains of Streptococcus pneumoniae, and commonly isolated Gram-negative organisms, including ceftriaxone-susceptible Enterobacteriaceae. We evaluated the in vitro activity of ceftaroline and selected comparator agents against bacterial isolates collected from patients with acute bacterial skin and skin structure infections (ABSSSIs) in the USA. A total of 6222 isolates were collected from 67 medical centers distributed across all nine USA census regions between 2009 and 2011 and tested for susceptibility by reference broth microdilution methods. Ceftaroline was very active against S. aureus (MIC50/90, 0.5/1 μg/mL; 99.6% susceptible), including MRSA (MIC50/90, 0.5/1 μg/mL; 99.1% susceptible). Against β-hemolytic streptococci, the activity of ceftaroline (MIC50/90, ≤0.015/0.03 μg/mL; 100.0% susceptible) was comparable to that of both penicillin (MIC50/90, ≤0.06/≤0.06 μg/mL; 100.0% susceptible) and ceftriaxone (MIC50/90, ≤0.25/≤0.25 μg/mL; 100.0% susceptible). Ceftaroline was also highly active against viridans group streptococci (MIC50/90, 0.03/0.06 μg/mL). Similar to ceftriaxone and ceftazidime, ceftaroline was active against wild-type strains of Escherichia coli (MIC50/90, 0.12/0.25 μg/mL; 94.0% susceptible) and Klebsiella pneumoniae (MIC50/90, 0.12/0.25 μg/mL; 96.8% susceptible); however, the ceftaroline activity was compromised among strains with an extended-spectrum β-lactamase-phenotype (MIC50/90, >32/>32 μg/mL for both E. coli and K. pneumoniae). In summary, ceftaroline showed potent activity against a large contemporary collection (6222) of bacterial isolates associated with ABSSSI in the USA.

Frequency of bacterial isolates and pattern of antimicrobial resistance in patients with hematological malignancies: A snapshot from tertiary cancer center.

Infections are the most important cause of mortality in patients with high-risk febrile neutropenia. Emergence of multi-drug resistant organisms (MDROs) has become a major challenge for hemato-oncologists. Knowledge of the prevalent organisms and their antimicrobial sensitivity can help deciding the empirical therapy at individual centers and allows timely measures to reduce the risk of antimicrobial resistance. To evaluate the frequency of bacterial isolates from all the samples and the pattern of bacterial bloodstream infections and incidence of MDROs. This is a retrospective analysis from a tertiary care cancer center. From January to June 2014 information on all the samples received in Department of Microbiology was collected retrospectively. The data from samples collected from patients with hematological cancers were analyzed for types of bacterial isolates and antimicrobial sensitivity. A total of 739 isolates were identified with 67.9% of isolates being Gram-negative. The predominant Gram-negative organisms were Escherichia coli, Psuedomonas spp. and Klebsiella spp. Among the bacterial bloodstream infections, 66% were Gram-negative isolates. MDROs constituted 22% of all isolates in blood cultures. Incidence of resistant Gram-positive organisms was low in the present dataset (methicillin resistant Staphylococcus aureus and vancomycin-resistant enterococci-1.3%). The analysis reconfirms the Gram-negative organisms as the predominant pathogens in bacteremia seen in patients with hematological cancers. The high frequency of multi-drug resistance in the dataset calls for the need of emergency measures to curtail further development and propagation of resistant organisms.

Antimicrobial resistance: a global view from the 2013 World Healthcare-Associated Infections Forum.

Antimicrobial resistance (AMR) is now a global threat. Its emergence rests on antimicrobial overuse in humans and food-producing animals; globalization and suboptimal infection control facilitate its spread. While aggressive measures in some countries have led to the containment of some resistant gram-positive organisms, extensively resistant gram-negative organisms such as carbapenem-resistant enterobacteriaceae and pan-resistant Acinetobacter spp. continue their rapid spread. Antimicrobial conservation/stewardship programs have seen some measure of success in reducing antimicrobial overuse in humans, but their reach is limited to acute-care settings in high-income countries. Outside the European Union, there is scant or no oversight of antimicrobial administration to food-producing animals, while evidence mounts that this administration leads directly to resistant human infections. Both horizontal and vertical infection control measures can interrupt transmission among humans, but many of these are costly and essentially limited to high-income countries as well. Novel antimicrobials are urgently needed; in recent decades pharmaceutical companies have largely abandoned antimicrobial discovery and development given their high costs and low yield. Against this backdrop, international and cross-disciplinary collaboration appears to be taking root in earnest, although specific strategies still need defining. Educational programs targeting both antimicrobial prescribers and consumers must be further developed and supported. The general public must continue to be made aware of the current scale of AMR’s threat, and must perceive antimicrobials as they are: a non-renewable and endangered resource.

Ceftaroline fosamil: a brief clinical review.

Ceftaroline is a novel cephalosporin with a favorable tolerability profile and broad in vitro activity against many resistant Gram-positive and common Gram-negative organisms. Ceftaroline fosamil is the first cephalosporin to be approved by the United States Food and Drug Administration (FDA) for the treatment of adults with acute bacterial skin and soft tissue infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). It is also approved by the FDA for the treatment of adults with community-acquired bacterial pneumonia, including cases caused by Streptococcus pneumoniae (with or without concurrent bacteremia), although there are no data at this time to support the use of ceftaroline fosamil for the treatment of pneumonia caused by MRSA. Ceftaroline fosamil is likewise approved by the European Commission for the treatment of adults with complicated skin and soft tissue infections or community-acquired pneumonia. This review summarizes the pharmacokinetic and microbiologic properties of ceftaroline, as well as the safety and efficacy data that led to its approval by the FDA in 2010 and the European Commission in 2012. Future directions to be addressed are also highlighted.