Aerobic Gram-negative Organisms Research Articles

The Effect of a Single-Dose Aminoglycoside With a Beta-Lactam for the Treatment of Gram-Negative Bacteremia.

Introduction: Aminoglycosides possess activity against aerobic gram-negative organisms and are often used in combination with beta-lactam antibiotics. Previous studies evaluating combination therapy in gram-negative bacteremia have not shown clear benefits, however antimicrobial resistance was not prevalent in these studies. Our objective is to elucidate potential benefits of adding a single dose of an aminoglycoside to a beta-lactam in patients with gram-negative bacteremia. Methods: This study was a single-center, retrospective, cohort study including patients 18 years old or older and treated for at least 24 hours for a confirmed gram-negative bacteremia. Patients were divided into two groups: receipt of beta-lactam monotherapy (n = 164) and receipt of a beta-lactam in addition to a single dose of an aminoglycoside (n = 79) within 24 hours of bacteremia onset. The primary endpoint was infection-related 30-day mortality per provider documentation. Key secondary outcomes include incidence of acute kidney injury (AKI) and time to improvement of AKI. Data were analyzed using Chi-square or Fisher's exact tests, student's T test, and descriptive statistics as appropriate. Results: The primary outcome occurred in 13/164 vs 2/79 patients in the monotherapy and combination groups (P = 0.10). Incidence of AKI (14% vs. 12%) and time to recovery from AKI (90 hours; IQR [50 - 133] vs 78 hours; IQR [42 - 128]) were comparable between groups (P = 1.00 and P = 0.73, respectively). Conclusions: The addition of a single-dose aminoglycoside was not significantly associated with reduced mortality or increased time to recovery from AKI in our patient population. Larger studies, particularly in more severely ill patient populations, are needed.

A comparison of treatment outcomes for levofloxacin versus doxycycline plus metronidazole for first-line treatment of uncomplicated pelvic inflammatory disease

Background: Pelvic inflammatory disease (PID), a common condition among women of reproductive age caused by various aerobic and anaerobic organisms, may sometimes lead to complications such as infertility, ectopic pregnancy, and chronic pelvic pain. Moxifloxacin is a broad-spectrum bactericidal acting against many Gram-positive, Gram-negative aerobic organisms and anaerobes. Rapid absorption and high bioavailability allow single daily dosing and improves compliance. Aims and Objectives: The present study was done to compare the treatment outcomes for levofloxacin versus doxycycline plus metronidazole for first-line treatment of uncomplicated in PID patients. Materials and Methods: This was hospital-based prospective, randomized, double-blind study conducted at gynecology outpatient department of Gouri Devi Institute of Medical Sciences and Hospital, Durgapur, West Bengal, from January 2019 to December 2019. The study group was divided into Group A 50 cases (receiving levofloxacin) and Group B 50 cases (receiving doxycycline plus metronidazole) were included in the study. Template was generated and analysis was done on SPSS software. Results: Among 50 patients of each group, mean age of the patients of Group A was 27.80 (±3.58) and mean age of Group B was 27.57 (±4.51). Mean parity of the patients of Group A was 1.93 (±1.11) and mean parity of Group B was 2.07 (±1.11). Past H/O PID in Group A was 17 and in Group B was 19. Visual analog scale (VAS) pain score of Group A was 3.80 (±1.827) and VAS pain score of Group B was 3.97 (±1.671). VAS pain score was 1.10 (±0.960) in Group A and 2.63 (±1.426) in Group B. VAS vaginal discharge was 1.40 (±1.276) in Group A and 3.00 (±1.619) in Group B. Conclusion: The management of uncomplicated PID requires broad-spectrum antibiotic regimens to cover all potential pathogens. This study confirmed that fluoroquinolones, specifically levofloxacin, are effective and well tolerated in the treatment of uncomplicated PID.

Clinical experience using cefiderocol

HintergrundInfektionen mit antibiotikaresistenten Bakterien stellen eine hohe Gesundheitsbelastung dar, da sie mit erhöhter Letalität assoziiert sind und längerfristige dramatische Beeinträchtigungen der Lebensqualität hervorrufen können. In Deutschland erkranken jährlich etwa 54.500 Menschen an Infektionen durch antibiotikaresistente Erreger, von denen etwa 2400 Menschen versterben. Infektionen mit multiresistenten gramnegativen Bakterien (MRGN), insbesondere mit carbapenemresistenten Erregern, stellen ein besonderes Risiko dar, da nur eine begrenzte Zahl an Therapieoptionen verfügbar ist.FragestellungWie sind die Ergebnisse aus Studien und Compassionate-Use-Programm mit dem neuen Siderophorantibiotikum Cefiderocol, das im April 2020 von der Europäischen Arzneimittel-Agentur (EMA) bei Erwachsenen zur Behandlung von Infektionen durch aerobe gramnegative Erreger zugelassen wurde, wenn nur begrenzte Behandlungsmöglichkeiten zur Verfügung stehen? Die Zulassung ist pathogenbasiert und fokusunabhängig [5].ErgebnisseCefiderocol, das über einen innovativen Zelleintrittsmechanismus verfügt, ist als erstes β‑Laktam-Antibiotikum aus der Gruppe der Cephalosporine stabil gegenüber allen klinisch relevanten β‑Laktamasen, einschließlich Carbapenemasen, und hat eine hohe In-vitro-Wirksamkeit gegenüber carbapenemresistenten MRGN. Die Ergebnisse werden durch klinische Studien bei komplizierten Harnwegsinfektionen, nosokomialer Pneumonie/Beatmungspneumonie und schweren Infektionen durch carbapenemresistente Erreger bestätigt.FazitKlinische Studiendaten sowie die Ergebnisse aus den weltweiten Erfahrungsberichten zeigen, dass Cefiderocol eine vielversprechende Behandlungsoption für schwere Infektionen durch multiresistente, insbesondere carbapenemresistente gramnegative Bakterien darstellt.

1274. Activity of Ceftolozane/Tazobactam, Imipenem/Relebactam, and Comparators Against Pseudomonas aeruginosa Isolates from Patients with Bloodstream and Other Infection Types—SMART United States/Canada 2018-2019

BackgroundCeftolozane/tazobactam (C/T), an antipseudomonal cephalosporin combined with a β-lactamase inhibitor, was approved for treatment of complicated urinary tract (cUTI) and intraabdominal infections (cIAI), and hospital-acquired/ventilator-associated bacterial pneumonia (HAP/VAP). Imipenem/relebactam (IMI/REL) is a combination of imipenem/cilastatin with relebactam, an inhibitor of class A and C β-lactamases. IMI/REL was approved for HAP/VAP and for infections due to aerobic gram-negative organisms in adults with limited treatment options (e.g., cUTI, cIAI). We compared the activity of C/T and IMI/REL against P. aeruginosa from bloodstream infections (BSI) to those from other infection types.MethodsAs part of the SMART program, 24 hospitals in the US and 8 in Canada each collected up to 250 consecutive gram-negative isolates per year in 2018-2019 from patients with BSI, lower respiratory tract infections (LRTI), IAI, and UTI. A total of 2351 Pa isolates were collected. MICs were determined using CLSI broth microdilution and breakpoints.Results Pa isolates from BSI tended to show higher susceptibility than IAI, UTI, and especially LRTI isolates (Table). Susceptibility to the tested comparator β-lactams was 11-12 percentage points lower among LRTI than BSI isolates, while C/T and IMI/REL susceptibility was only 2-5% lower. Even among BSI isolates, the comparator β-lactams were active against only 75-88% of isolates, while C/T and IMI/REL were active against >95%. Only amikacin showed higher activity. Analyzing coverage by either C/T or IMI/REL, 98.7% of Pa isolates from BSI were susceptible to one or both agents. C/T and IMI/REL maintained activity against 89% and 69% of meropenem-nonsusceptible (MEM-NS) Pa isolates from BSI (n=36), respectively, and 87% and 76% of piperacillin/tazobactam (P/T)-NS Pa (n=38).Results Table ConclusionEven among BSI isolates, which were generally more susceptible than those from other infection types, Pa susceptibility to commonly used β-lactams like MEM and P/T was < 90%, 7-23% lower than C/T and IMI/REL. Given the desirability of β-lactams among clinicians and the >98% coverage by either C/T or IMI/REL of Pa isolates from BSI, both agents represent important options in the treatment of patients with BSI.Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Kelly Harris, PharmD, BCPS, Merck & Co. Inc (Employee) Katherine Young, MS, Merck (Employee) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

Determination of ten aminoglycoside residues in eggs by mixed-mode ion exchange liquid chromatography-tandem mass spectrometry

该研究系统地优化了样品前处理过程及仪器分析中影响氨基糖苷残留分析准确度与灵敏度的各主要因素,建立了鸡蛋中10种氨基糖苷类药物(链霉素、双氢链霉素、潮霉素B、卡那霉素、阿米卡星、妥布霉素、安普霉素、大观霉素、新霉素、庆大霉素)残留量的混合型离子交换液相色谱-串联质谱分析方法。样品经10 mmol/L乙酸铵缓冲溶液(含0.4 mmol/L EDTA和50 g/L三氯乙酸)超声提取,调节pH至6~7后,经PRiME HLB固相萃取柱富集净化,采用SIELC Obelisc R色谱柱分离,以乙腈和1.0%(v/v)甲酸水溶液(含1 mmol/L甲酸铵)为流动相进行梯度洗脱,在正离子、多反应监测模式下经串联质谱仪测定,外标法定量。该方法在5~200 μg/L质量浓度范围内线性关系良好,相关系数(r2)均大于0.99;方法的检出限(LOD, S/N≥3)为2~5 μg/kg,定量限(LOQ, S/N≥10)为5~10 μg/kg。在空白鸡蛋中进行LOQ、20 μg/kg、100 μg/kg 3个水平的加标回收实验,方法的平均回收率(n=6)为68.1%~111.3%,相对标准偏差为1.2%~12.3%。利用该方法对市售的20批次鸡蛋样品进行测定,均未检出目标物。本方法简单、灵敏、准确,可实现鸡蛋中10种氨基糖苷类药物残留的批量检测。

Ceftazidime-Avibactam for the Treatment of Serious Gram-Negative Infections with Limited Treatment Options: A Systematic Literature Review.

IntroductionA systematic literature review was undertaken to evaluate real-world use of ceftazidime-avibactam for infections due to aerobic Gram-negative organisms in adults with limited treatment options.MethodsLiterature searches retrieved peer-reviewed publications and abstracts from major international infectious disease congresses from January 2015 to February 2021. Results were screened using pre-defined criteria to limit the dataset to relevant publications (notable exclusions were paediatric data and outcomes data for bacteria intrinsically resistant to ceftazidime-avibactam). Data for included publications were subjected to qualitative synthesis.ResultsSeventy-three relevant publications (62 peer-reviewed articles; 10 abstracts) comprising 1926 patients treated with ceftazidime-avibactam (either alone or combined with other antimicrobials) and 1114 comparator/control patients were identified. All patients were hospitalised for serious illness and most had multiple comorbidities. The most common infections were pneumonia, bacteraemia, and skin/soft tissue, urinary tract, or abdominal infections; smaller numbers of patients with meningitis, febrile neutropenia, osteomyelitis, and cystic fibrosis were also included. Carbapenem-resistant or carbapenemase-producing Enterobacterales (CRE; n = 1718) and carbapenem-resistant, multidrug-resistant (MDR), and extensively drug-resistant Pseudomonas aeruginosa (n = 150) were the most common pathogens. Most publications reported positive outcomes for ceftazidime-avibactam treatment (clinical success rates ranged from 45 to 100% and reported 30-day mortality from 0 to 63%), which were statistically superior versus comparators in some studies. ceftazidime-avibactam resistance emergence occurred infrequently and mostly in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains.ConclusionThis review provides qualitative evidence of successful use of ceftazidime-avibactam for the treatment of hospitalised patients with CRE and MDR P. aeruginosa infections with limited treatment options.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00507-6.

Compassionate use of cefiderocol for carbapenem-resistant Acinetobacter baumannii prosthetic joint infection.

BackgroundCefiderocol is a recently licensed novel siderophore-conjugated cephalosporin stable to hydrolysis by serine and MBLs. It has been successfully used to treat Enterobacterales infections and is approved for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.ObjectivesTo describe the compassionate use of cefiderocol and clinical outcome in a case of prosthetic joint infection due to MDR Acinetobacter baumannii.Patients and methodsThis case study follows a 66-year-old woman who sustained an open fracture of the left distal humerus in Pakistan. She underwent open reduction and internal fixation and on return to the UK presented to hospital with a discharging surgical wound.ResultsDebridement of her wound cultured NDM carbapenemase-producing A. baumannii susceptible to colistin, tobramycin and tigecycline only. She developed vomiting with acute kidney injury with colistin and tigecycline. Antimicrobial efficacy of cefiderocol was predicted from in vitro and in vivo susceptibility tests. A successful request was made to Shionogi for compassionate use of cefiderocol, which was added to tigecycline. Cefiderocol was well tolerated with no toxicity and improved renal function. In total she received 25 days of cefiderocol and continued on tigecycline for a further 6 weeks in the community. She has well-healed wounds and good range of elbow movement.ConclusionsCefiderocol’s novel mode of cell entry is effective against MDR Gram-negative bacteria with reduced toxicity compared with other last line antibiotics. Our case demonstrates that cefiderocol may be useful as therapy for patients with limited treatment options due to antimicrobial resistance. The prescribing information for cefiderocol is available at: https://shionogi-eu-content.com/gb/fetcroja/pi.

Imipenem/cilastatin sodium/relebactam fixed combination to treat urinary infections and complicated intra-abdominal bacterial infections.

Imipenem/cilastatin sodium/relebactam is a combination of imipenem/cilastatin, a U.S. Food and Drug Administration (FDA)-approved antibiotic, and β-lactamase inhibitor relebactam which has been developed for the treatment of complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) due to drug-resistant bacterial pathogens. The combination (Recarbrio) has been designated as a qualified infectious disease product (QIDP) and obtained FDA approval in 2019 for the treatment of cUTI and cIAI caused by susceptible Gram-negative microorganisms in adult patients with limited or no alternative treatment options. The product was also approved by the European Medicines Agency (EMA) in 2020 for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.

PIN9 CEFTAZIDIME-AVIBACTAM FOR THE TREATMENT OF INFECTIONS DUE TO AEROBIC GRAM-NEGATIVE ORGANISMS IN PATIENTS WITH LIMITED TREATMENT OPTIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS

To evaluate the effectiveness of ceftazidime-avibactam (CAZ-AVI) compared to colistin for the treatment of infections due to aerobic Gram-negative organisms in adult patients with limited treatment options, in particular multi-drug resistant (MDR) Enterobacteriaceae and Pseudomonas infections. An electronic search was conducted in Medline, EMBASE and ClinicalTrials.gov databases up to June 2018. Data were screened, extracted and appraised independently. Both random-controlled and non-controlled studies were eligible for inclusion providing that data were available on clinical cure, mortality and/or adverse events in patients with MDR Enterobacteriaceae or Pseudomonas infections treated with CAZ-AVI or colistin. A meta-regression was performed to estimate treatment effect of CAZ-AVI compared to colistin, adjusted for study design, using R software. Direct and indirect comparisons were pooled through a random-effect meta-analysis weighted by inverse variance method. Heterogeneity between studies was assessed with χ2 and I2 tests. Overall, 804 references were retrieved from electronic search. After screening, a total of 37 studies (evaluating 361 patients treated with CAZ-AVI and 1,363 treated with colistin) meet inclusion criteria (24 studies in Enterobacteriaceae, 16 in Pseudomonas and 3 studies reported results for both infections). In patients with carbapenem-resistant Enterobacteriaceae infections, CAZ-AVI was associated with higher clinical cure (Odds Ratio [OR]: 1.99; 95%CI: 0.99-4.04) and lower 30-day mortality (OR: 0.79; 95%CI: 0.42-1.48) in comparison to colistin. In patients with MDR Pseudomonas infections, the OR also favored CAZ-AVI over colistin for both clinical cure (OR: 1.27; 95%CI: 0.19-10.81) and 30-day mortality (OR:0.69; 95%CI: 0.16-3.07). The mean proportion of colistin-treated patients with nephrotoxicity and neurotoxicity was 26% and 3%, respectively. Despite the scarcity of data and methodological limitations of the analysis, the available evidence suggests that CAZ-AVI is associated with a better efficacy and safety profile compared to colistin in patients with limited therapeutic options for infections caused by Gram-negative aerobic organisms.

PIN46 CONTRASTING AVAILABLE THERAPY FOR PATIENTS WITH LIMITED OPTIONS DUE TO EXTREMELY DRUG-RESISTANCE BACTERIA WITH A NOVEL OPTION FOR COMPLICATED NOSOCOMIAL INFECTIONS

Appraise the economic value of introducing a novel antimicrobial in the Mexican Healthcare System for hospitalized patients with limited treatment options due to infections caused by aerobic Gram-negative organisms resistant to available therapies. An economic model was developed comparing the available therapy for patients with limited options, colistin+carbapenem, with ceftazidime/avibactam (CAZ-AVI), an extended-spectrum cephalosporin along with a novel non-β-lactam β-lactamase inhibitor. Outcomes were measured as proportion of cured patients and proportion of alive patients, considering the critical need of new treatments due to antimicrobial resistance. The cost-effectiveness model was performed with an institutional perspective. Mexican public institutional costs and resource use for disease and its complications, including adverse events treatments, were considered. The time horizon in the model considered average length of treatment for CAZ-AVI and the assessed comparator. Deterministic and probabilistic sensitive analyses were conducted in order to evaluate robustness of clinical and economic outcomes. CAZ-AVI offers an incremental clinical cure cost of –USD 1,578 (USD 3,861 – USD 5,439) in the treatment of complicated infections; the proportion of cured patients being 85% versus 40% for CAZ-AVI and colistin+carbapenem respectively, this results in a lower cost per healed patient of USD 4,542 with CAZ-AVI versus USD 13, 596 with colistin+carbapenem. Also, CAZ-AVI is a dominant alternative considering overall survival of 92% with USD 4,196 cost per live patient versus 55% with USD 9,888 of colistin+carbapenem cost. CAZ-AVI is a cost-saving alternative in the treatment of complicated infections caused by multidrug-resistant pathogens in patients with limited treatment options due to estimated higher cure and survival rates and a lower rate of adverse events (i.e. renal failure). Due to increasing antimicrobial resistance, the adequate use of ceftazidime/avibactam represents a feasible alternative for Mexican public sector following WHO recommendations in the Global Action Plan on Antimicrobial Resistance.

131. Duration of Therapy for the Treatment of Gram-Negative Bloodstream Infections

BackgroundWhile current guidelines suggest a total treatment duration of 7 to 14 days for gram-negative bloodstream infections (GN-BSI), there is mounting evidence to suggest that shorter durations may be sufficient. This study compared the treatment outcomes of patients who received short duration therapy (6–10 days) with those who received long durations (11–15 days).MethodsThis was a retrospective study of adult patients who grew an aerobic gram-negative organism from a blood culture while admitted at Strong Memorial Hospital between May 2016 and May 2018. The primary outcome was a composite of mortality and relapsed GN-BSI with the same organism within 90 days of index culture. Secondary outcomes included clinical resolution at end of therapy (EOT), length of stay (LOS), 30-day readmission rate, Clostridoides difficile infection (CDI), development of recurrent GN-BSI resistant to prior antibiotic therapy, and development of multi-drug-resistant (MDR) GN-BSI within 90 days. Appropriate therapy was defined as an antibiotic with confirmed in vitro susceptibility that was either parenteral or a highly bioavailable oral antibiotic (fluoroquinolones or sulfamethoxazole–trimethoprim).ResultsOf 600 patients screened, 116 were included in the long duration group and 34 patients in the short-duration group. The majority of patients had a urinary source of infection (59.3%). The primary composite outcome occurred in 11.8% of the short duration group compared with 10.3% in the long (P > 0.999). There was no difference in clinical resolution at EOT, LOS, or rates of CDI, MDR GN-BSI, recurrent GN-BSI resistant to prior therapy, or 30-day readmission. Patients in the long duration group were discharged with longer appropriate outpatient courses (8 days vs. 0.5 days, P < 0.001), which remained significant when including lower bioavailability agents (e.g., oral β lactams) (8 days vs. 5 days, P < 0.001).ConclusionThere was no difference in clinical outcomes between the long and short duration therapy for treatment of GN-BSI. This study may support shorter treatment durations for uncomplicated GN-BSI, but should be interpreted cautiously given the smaller sample size.Disclosures All authors: No reported disclosures.

Manipulation of the microbiota to eradicate multidrug-resistant Enterobacteriaceae from the human intestinal tract

Manipulation of the microbiota to eradicate multidrug-resistant Enterobacteriaceae from the human intestinal tract

1050. Oral Antibiotics for the Treatment of Gram-Negative Bloodstream Infections: Prescribing Practices and Outcomes at a Large Academic Medical Center

BackgroundThere is limited data to guide the use of oral (PO) antibiotics for the treatment of Gram-negative (GN) bloodstream infection (BSI). The objective of this study was to describe the characteristics and outcomes at a large academic medical center.MethodsRetrospective observational cohort of adult patients (age ≥18 years) with at least one blood culture positive for aerobic Gram-negative organism(s) treated with antibiotic therapy (IV or oral [PO]) at University of Medical Center from November 2015 to May 2017. Oral antibiotics were described based on bioavailability. The primary outcome of interest was 30-day infection-related readmission. Secondary objectives included evaluation of patient characteristics associated with PO antibiotic use.ResultsDuring the defined study period 310 patients met inclusion; 113 (36.5%) were switched to PO antibiotic therapy for the treatment of GN BSI within a median of 5 (IQR 3–11) days. Oral antibiotics were initiated at discharge for 50 (44%) of patients switched. Patients switched to PO were less likely to have has a stay in the ICU (24.8% vs. 47.7%, P < 0.0001) and were less likely to have an ID consult (57.5% vs. 71.1%, P = 0.034). There was no difference in median Charlson Comorbidity Score (2, IQR 0–4). The most common sources of infection among those switched to PO agents were urinary (50, 44.2%) and intra-abdominal (25, 22.1%). The majority of patients were placed on a PO agent with high bioavailability (61, 54%), which included levofloxacin and moxifloxacin. There was a slightly higher proportion of use of high (vs. low) bioavailable antibiotics in patients with ID consult compared with those without (59% vs. 41%, P = 0.053). PO antibiotics were more frequently prescribed for patients discharged home (78, 69%) compared with patients discharged to Rehab/Short-term facility (28, 24.8%). Thirty-day hospital readmission was more common among the patients treated with PO antibiotics (18.6 vs. 8.1%, P = 0.006); however, ID-related readmission was rare (0.9% vs. 1%, P = 0.91).ConclusionUrinary and intra-abdominal sources and home discharge were common among those with PO antibiotic use. ID-related outcomes were similar among those treated with IV vs. PO agents. More research is necessary to determine optimal time to PO antibiotic switch.Disclosures K. Claeys, Nabriva: Scientific Advisor, Consulting fee. Melinta: Scientific Advisor, Consulting fee. E. Heil, ALK-Abelló: Grant Investigator, Research grant.

Gram-negative multi-drug resistant bacteria influence survival to discharge for horses with septic synovial structures: 206 Cases (2010–2015)

Bacterial colonization of synovial structures can cause infections that are difficult to treat. Systemic and local antimicrobials and repeated joint lavages are the mainstays of therapy. However, despite aggressive treatments, infection may persist, leading to significant tissue damage or death of the patient. In order to investigate the impact of bacterial culture and antimicrobial resistance on survival to discharge, we reviewed medical records of horses admitted to the University of Pennsylvania’s large animal teaching hospital from 2010–2015. Two-hundred and six cases with a definitive diagnosis of septic synovitis and a synovial fluid sample submitted for microbiological culture were included in the study. Of these horses, 48% were culture negative and 52% were positive for any bacterial growth, of which 66% were gram-positive and 28% were gram-negative aerobic organisms with 4% anaerobic and 2% fungal organisms. Overall survival to discharge from hospital was 86%. Horses that had negative growth on culture were more likely to survive until discharge (p < 0.02). Multivariable analyses revealed that the likelihood of euthanasia was significantly associated with identification of coagulase positive Staphylococcus spp. (OR 7.66, 5.46–10.74, p < 0.0001), β-hemolytic Streptococcus spp. (OR 5.18, 3.56–7.55, p < 0.0001), Enterococcus spp. (OR 18.38, 11.45–29.52, p = 0.002), Enterobacteriaceae (OR 31.37, 22.28–44.17, p < 0.0001), Pseudomonas aeruginosa (OR 9.31, 5.30–16.34, p = 0.0004) or other gram-negative species (OR 3.51, 2.07–5.94, p = 0.001). Multi-drug resistance and gram-negative bacteria species were associated with significantly decreased survival rates (OR 119.24, 70.57–201.46, p < 0.0001). In conclusion, prognosis for survival to discharge was poor for horses that were infected with gram-negative organisms, particularly those with MDR phenotypes.

Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections.

Ceftazidime-avibactam (Zavicefta®) is an intravenously administered combination of the third-generation cephalosporin ceftazidime and the novel, non-β-lactam β-lactamase inhibitor avibactam. In the EU, ceftazidime-avibactam is approved for the treatment of adults with complicated urinary tract infections (cUTIs) [including pyelonephritis], complicated intra-abdominal infections (cIAIs), hospital-acquired pneumonia (HAP) [including ventilator-associated pneumonia (VAP)], and other infections caused by aerobic Gram-negative organisms in patients with limited treatment options. This article discusses the in vitro activity and pharmacological properties of ceftazidime-avibactam, and reviews data on the agent's clinical efficacy and tolerability relating to use in these indications, with a focus on the EU label. Ceftazidime-avibactam has excellent in vitro activity against many important Gram-negative pathogens, including many extended-spectrum β-lactamase-, AmpC-, Klebsiella pneumoniae carbapenemase- and OXA-48-producing Enterobacteriaceae and drug-resistant Pseudomonas aeruginosa isolates; it is not active against metallo-β-lactamase-producing strains. The clinical efficacy of ceftazidime-avibactam in the treatment of cUTI, cIAI and HAP (including VAP) in adults was demonstrated in pivotal phaseIII non-inferiority trials with carbapenem comparators. Ceftazidime-avibactam treatment was associated with high response rates at the test-of-cure visit in patients with infections caused by ceftazidime-susceptible and -nonsusceptible Gram-negative pathogens. Ceftazidime-avibactam was generally well tolerated, with a safety and tolerability profile consistent with that of ceftazidime alone and that was generally typical of the injectable cephalosporins. Thus, ceftazidime-avibactam represents a valuable new treatment option for these serious and difficult-to-treat infections.

Bacterial isolates and antimicrobial susceptibilities from odontogenic abscesses in rabbits: 48 cases

The medical record database of a veterinary teaching hospital was searched from 2000 through 2014 for records of client-owned rabbits with positive cultures from odontogenic abscesses. Data reviewed included sex,...

COMMUNITY AQUIRED PNEUMONIA IN ADULTS: POSSIBILITIES OF TREATMENT IN OUTPATIENT CONDITIONS

Community-acquired pneumonia (CAP) is a common and poorly diagnosed disease in the outpatient setting. The decision on hospitalization of the patient or treating him at home is the most important clinical conclusion made by the doctor in the course of the disease. Patients with non-severe course of CAP with the medical point of view are treated on an outpatient basis. Assessment of the severity of the patient CAP is based on the predictive Confusion-Respiratory rate – Blood pressure (CRB)-65 and criteria of systemic inflammatory response syndrome (SVR). CAP patients with a scale CRB 65 score 1 or more and/or syndrome SVR are hospitalized on an emergency basis. In accordance with the national guidelines for VAP amoxicillin is used to treat uncomplicated CAP as monotherapy (Group 1 included CAP patients). Amoxicillin is stable in an acidic environment and food intake doesn’t affect the drug absorption. Amoxicillin binds to plasma proteins by about 20% and easily permeates through histohematic barriers. The drug is active against aerobic gram-positive respiratory Staphylococcus spp. (except those strains producing penicillinase), Streptococcus pneumoniae and aerobic gram-negative respiratory organisms (Haemophilus influenzae, Escherichia coli, some strains of Klebsiella).

Impact of Two Different Antimicrobial Stewardship Methods on Frequency of Streamlining Antimicrobial Agents in Patients with Bacteremia.

OBJECTIVE To assess the likelihood of antimicrobial streamlining between 2 antimicrobial stewardship methods. DESIGN Retrospective cohort study. SETTING Large academic medical center. METHODS Frequency and time to antimicrobial streamlining were compared during a prior authorization and a prospective audit period. Streamlining was defined as an antimicrobial change to a narrower agent if available or to a broader agent if the isolate was resistant to empiric therapy. Patients included were ≥18 years old with monomicrobial bacteremia with S. aureus, Enterococcus spp., or any aerobic Gram-negative organism. RESULTS A total of 665 cases of bacteremia met inclusion criteria. Frequency of streamlining was similar between periods for all cases of bacteremia (audit vs restriction: 60.7% vs 53.2%; P=.12), S. aureus bacteremia (73.2% vs 76.9%; P=.671), and Enterococcus bacteremia (81.6% vs 71.9%; P=.335). Compared to restriction, the audit period was associated with an increased frequency of streamlining for cases of Gram-negative bacteremia (51.4% vs 35.6%; odds ratio [OR], 1.85; 95% confidence interval [CI], 1.06-3.25), those on the medical service (67.9% vs 53.1%; OR, 1.86; 95% CI, 1.09-3.16), and those admitted through the emergency department (71.6% vs 51.4%; OR, 2.32; 95% CI, 1.24-4.34). Characteristics associated with increased streamlining included: absence of β-lactam allergy (P<.001), Gram-negative bacteremia (P<.001), admission through the emergency department (P=.001), and admission to a medical service (P=.011). CONCLUSIONS Compared with prior authorization, prospective audit increased antimicrobial streamlining for cases of Gram-negative bacteremia, those admitted through the emergency department, and those admitted to a medical but not surgical service. Infect Control Hosp Epidemiol 2016:1-7.

Native Mitral Valve Endocarditis Caused by Neisseria elongata subsp. nitroreducens in a Patient with Marfan Syndrome: First Case in Italy and Review of the Literature.

Neisseria elongata (NE) is an aerobic Gram-negative organism that constitutes part of the commensal human normal oropharyngeal flora. Although previously considered not to be pathogenic, it has been recognized as an occasional cause of significant infections in humans. We report here the first case in Italy of infective endocarditis of a native prolapsing mitral valve in a patient with Marfan syndrome, caused by NE subspecies nitroreducens which has been rarely isolated from clinical specimens. The culprit organism has been confirmed by mass spectrometry directly from the positive blood culture, as previously reported. The amplified gene has been deposited in GenBank under accession number KT591873. In spite of the reported aggressive nature of NE, clinical remission was promptly obtained, there being no requirement for surgery.

Direct Identification of Aerobic Bacteria by Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry Is Accurate and Robust.

Bacterial identification in the clinical laboratory can be laborious and expensive. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a rapid and cost-effective diagnostic tool for the identification of organisms routinely found in the microbiology laboratory. The objective of this study was to demonstrate that identification of aerobic Gram-positive and Gram-negative organisms could be performed accurately and efficiently by MALDI-TOF MS and the Bruker Biotyper system without the use of time-consuming extraction methodologies. Isolates previously recovered by routine culture and workup from clinical specimens were cultured to appropriate media, identified directly by MALDI-TOF MS, and compared to results from various biochemical identification methods. Using the direct-smear method, 99.5% and 98.0% of aerobic Gram-negative and Gram-positive bacteria, respectively, were identified to the genus level. At a score of ≥1.9, 97.6% Gram-negative organisms and 94.6% Gram-positive organisms were correctly identified to the species level by direct-smear method. Only 1.1% of isolates required further reflex to direct-plate extraction. The direct-smear method proved to be robust, as various growth temperatures, media, culture age, and different operators had no notable impact on the bacterial identification rate. The direct-smear method is an accurate and time-saving method for routine species-level bacterial identification.