Microbiological Success Research Articles

Epidemiology of pneumococcal infections in hospitalised adult patients in Lebanon with a highlight on non-invasive disease.

Streptococcus pneumoniae causes a wide range of infections classified as invasive and non-invasive pneumococcal disease (non-IPD). We retrospectively reviewed over a decade the clinical course and outcome of 103 adult subjects infected with S. pneumoniae. The majority of the subjects (92%) were eligible for pneumococcal vaccination, however none were vaccinated. Most of the infective strains caused non-IPD (64%), with CAP being the leading primary infection (49%). Clinical success was achieved in 71% of the cases and microbiological success in 94% of the cases with available documented follow-up cultures. Yet, 19% of the subjects developed superinfections caused by extensive-drug resistant bacteria with the predominance of ventilator-associated pneumonia (13%). Total in-hospital mortality reached 27% and S. pneumoniae infection attributed mortality was 20%. Using multivariate logistic regression, kidney disease and septic shock were independent risk factors for mortality [Odd's Ratio (OR) = 14.96 (2.34-95.45), p = 0.004; OR = 5.09 (1.33-19.51), p = 0.02, respectively]. On comparing outcome between subjects with IPD and those with non-IPD, death attributed to S. pneumoniae infection was found to be significantly higher in subjects with IPD (23%, p = 0.023). Nevertheless, clinical success and total in-hospital mortality rates were not statistically different between the two groups (p = 0.056, p = 0.174, respectively). S. pneumoniae remains a pathogen causing considerable mortality. In adults, non-IPD should be considered of comparable importance as IPD. Increasing pneumococcal vaccine awareness at the healthcare professional and patient levels is essential for increasing vaccine uptake, thus decreasing the incidence, severity and sequelea of pneumococcal disease.

Clinical experience with ceftazidime/avibactam for treatment of antibiotic-resistant organisms other than Klebsiella pneumoniae

BackgroundCeftazidime/avibactam is a newly approved β-lactam/β-lactamase inhibitor combination with activity against antibiotic-resistant Gram-negative organisms, including many carbapenem-resistant strains. Although this agent may offer a promising treatment option for serious infections with limited alternatives available, clinical experience with ceftazidime/avibactam in treatment of infections caused by multidrug-resistant Gram-negative organisms other than Klebsiella pneumoniae is limited. MethodsA retrospective case series was performed to evaluate patients treated with ceftazidime/avibactam for infections caused by organisms other than K. pneumoniae at our institution over a 1-year period. Patients aged at least 18 years who received at least one dose of ceftazidime/avibactam were eligible for inclusion. Clinical and microbiological data were collected, and investigators assessed adverse effects, microbiological cure, clinical success, and 30-day in-hospital mortality following completion of ceftazidime/avibactam therapy. ResultsTen patients were included. The most common index infection was pneumonia (n = 6/13, 46%) and the most frequently isolated organism was Pseudomonas aeruginosa (n = 8/21, 38%). Fifty percent of patients received ceftazidime/avibactam as monotherapy. Microbiological cure was achieved in 67% (n = 6/9) of patients and 70% (n = 7/10) of patients met criteria for clinical success. The 30-day in-hospital mortality rate was 30%. No patients experienced adverse events because of ceftazidime/avibactam therapy. ConclusionsFor infections caused by antibiotic-resistant Gram-negative organisms other than K. pneumoniae, clinical and microbiological success rates for patients treated with ceftazidime/avibactam were similar to those that have been reported for K. pneumoniae. Ceftazidime/avibactam appears to be a promising treatment option for infections caused by a variety of resistant Gram-negative organisms when limited alternatives exist.

Ceftolozane-tazobactam and Fosfomycin for rescue treatment of otogenous meningitis caused by XDR Pseudomonas aeruginosa: Case report and review of the literature

Extensively drug resistant Pseudomonas aeruginosa (XDR-PA) strains with limited or absent residual antimicrobial susceptibility cause a growing burden of difficult-to treat infections. Treatment options are even more limited for patients with central nervous system (CNS) involvement, as colistin-based regimens are hampered by poor blood brain barrier penetration, being often associated with insufficient clinical and microbiological success. New treatment options are awaited, but evidence from prospective evidence-based evaluations is still lacking. Here we report a case of breakthrough otogenous meningitis caused by XDR-PA in a young patient treated with meropenem and colistin for XDR-PA bloodstream infection and pneumonia after a car-crash polytrauma. The patient was treated with off-label, high-dose ceftolozane-tazobactam and high-dose fosfomycin after characterization of CNS XDR-PA isolates, with rapid clinical and microbiological resolution of meningitis. Our experience, although based on a single case, lands preliminary support to the concept that rescue regimens including ceftolozane-tazobactam and fosfomycin may be considered for XDR-PA CNS infections in patients without alternative therapeutic options.

Retrospective analysis comparing oral stepdown therapy for enterobacteriaceae bloodstream infections: fluoroquinolones versus β-lactams

Enterobacteriaceae bloodstream infections (EB-BSIs) are a common manifestation of Gram-negative sepsis and are initially managed with empirical intravenous antibiotics. Upon stabilisation and source control, patients are often transitioned to an oral agent. Fluoroquinolones (FQs) plays a prominent role in stepdown therapy for severe infections owing to favourable pharmacokinetic parameters; however, serious adverse events (AEs) have been documented with their use. A total of 224 adults with EB-BSI initiated on empirical intravenous antibiotics with stepdown to oral β-lactam (BLM) (n = 84) or FQ (n = 140) were studied to compare clinical success and identify risk factors for treatment failure. Subgroups of early versus late oral stepdown and short versus extended duration of therapy (DOT) were assessed. Stepdown therapy with oral BLM was non-inferior to oral FQ (86.9% vs. 87.1%; mean difference 0.2%, 97.5% CI −10.3 to 10.7). Microbiological success (94.0% vs. 97.9%; P > 0.05) and 30-day re-admission (14.3% vs. 14.3%; P > 0.05) were similar. Patients were more likely to complete their BLM course without an AE compared with FQs (91.7% vs. 82.1%; P = 0.049). Clinical success was comparable between early and late stepdown (86.7% vs. 87.5%; P > 0.05) and short versus extended DOT (88.2% vs. 86.7%; P > 0.05). Negative predictors of clinical success identified by logistic regression were complicated diabetes (OR = 0.35, 95% CI 0.15–0.83) and urinary abnormality (OR = 0.39, 95% CI 0.16–0.94). These findings suggest that oral BLMs were non-inferior to FQs as stepdown therapy for EB-BSI, with less AEs.

A prospective observational treatment study of aerococcal urinary tract infection

ObjectivesAerococcus urinae and Aerococcus sanguinicola cause urinary tract infections (UTIs) and antibiotic treatment recommendations are solely based on in vitro findings and limited clinical experience. Our objective was to investigate the effectiveness of different treatment strategies in aerococcal UTI through a prospective observational study. MethodsUrine samples with aerococci were identified and patients were enrolled. The aerococci were subjected to Etests. Information on clinical symptoms, and the treatment given, was collected. Patients were interviewed after the conclusion of treatment to assess clinical cure and a control urine culture assessed the microbiological cure. ResultsOf 31,629 urine samples, 144 grew aerococci and fulfilled the inclusion criteria. 91 patients gave consent and the 72 patients with UTI were assessed for treatment outcome. 53 patients had A. urinae UTI, while 19 had A. sanguinicola UTI. Nitrofurantoin was most commonly prescribed, achieving clinical and microbiological success in 71/76% of cases of A. urinae UTI, and 42/50% of cases of A. sanguinicola UTI. Pivmecillinam achieved success in patients with A. urinae cystitis and ciprofloxacin in patients with pyelonephritis. ConclusionsOur results support that nitrofurantoin is a valid option for the treatment of cystitis caused by A. urinae.

Outcomes Comparing Initial Short vs Long Course Echinocandin Therapy in Patients with Candidemia Caused by Fluconazole Susceptible Strains

Background Guidelines for candidemia (CAND) treatment recommend initial echinocandin (ECHINO) therapy with transition to fluconazole (FLUC) after 5–7 days in patients with clinical stability, FLUC-susceptibility, and negative cultures; however, optimal timing for transition is unknown. In the era of rapid diagnostics and antimicrobial stewardship programs (ASP), studies are needed to evaluate the impact of earlier transition in CAND due to routinely FLUC-susceptible species.Methods Retrospective study of adult patients at NewYork-Presbyterian Hospital from 2012 to 2014. Inclusion criteria included ≥1 blood culture with C. albicans, C. tropicalis or C. parapsilosis, ≥1 dose ECHINO initial therapy, ≥3 days total treatment, and no prior episode of CAND within 30 days. Patients with polymicrobial bloodstream infection excluded. Patients de-escalated from ECHINO at ≤3 days (short-course; SC-ECH) were compared with those who received ≥4 days of ECHINO (long course; LC-ECH). The primary outcome was 14-day complete response (CR), defined as survival with clinical improvement and sterilization of blood cultures. Secondary outcomes included day 7 microbiological success (MicroS) and 28-day survival (SURV).Results76 patients included: 21 in SC-ECH, 55 in LC-ECH groups. C. albicans (58%) most common species. Majority were male (59%) with median age 64 years (IQR 49–74), 62% were in ICU at time of CAND, 50% had recent surgery. No significant baseline differences between SC-ECH and LC-ECH groups, including in PITT bacteremia score ≥4 (43% vs. 42%; P = 0.4) or median APACHE (20 vs. 20; P = 0.684). There was no difference between SC-ECH vs. LC-ECH in CR (52% vs. 49%; P = 1.0), early MicroS (81% vs. 87%; P = 0.484), or SURV (62% vs. 73%; P = 0.523). On multivariable analysis with duration of ECHINO therapy forced into the model, only PITT bacteremia score <4 remained an independent predictor of CR (OR 6.1, 95% CI 2.1, 17.9; P = 0.001).Conclusion In adult patients with CAND due to routinely FLUC-susceptible species, early de-escalation from ECHINO was associated with similar outcomes, including day 7 MicroS. Early de-escalation based on early species identification has the potential to be a target for ASPs to optimize antifungal therapy without compromising clinical outcomes.Disclosures All authors: No reported disclosures.

Treatment of Achromobacter Ventilator-Associated Pneumonia in Critically Ill Trauma Patients.

Achromobacter sp are nonfermenting Gram-negative bacilli (NFGNB) that rarely cause severe infections, including ventilator-associated pneumonia (VAP). Data on the treatment of Achromobacter pneumonia are very limited, and the organism has been associated with a high mortality rate. Thus, more data are needed on treating this organism. To evaluate the treatment of Achromobacter VAP in critically ill trauma patients. This retrospective, observational study evaluated critically ill trauma patients who developed Achromobacter VAP. A previously published pathway for the diagnosis and management of VAP was used according to routine patient care. This included the use of quantitative bronchoscopic bronchoalveolar lavage cultures to definitively diagnose VAP. A total of 37 episodes of Achromobacter VAP occurred in 34 trauma intensive care unit patients over a 15-year period. The most commonly used definitive antibiotics were imipenem/cilastatin, cefepime, or trimethoprim/sulfamethoxazole. The primary outcome of clinical success was achieved in 32 of 37 episodes (87%). This is similar to previous studies of other NFGNB VAP (eg, Pseudomonas, Acinetobacter) from the study center. Microbiological success was seen in 21 of 28 episodes (75%), and VAP-related mortality was 9% (3 of 34 patients). Achromobacter is a rare but potentially serious cause of VAP in critically ill patients. In this study, there was an acceptable success rate compared with other causes of NFGNB VAP in this patient population.

Quality changes and microbiological spoilage analysis of air-packed and vacuum-packed silver carp (Hypophthalmichthys molitrix ) fillets during chilled storage

The effects of air-packed (AP) and vacuum-packed (VP) on quality and microbial characteristics of silver carp (Hypophthalmichthys molitrix) fillets during chilled storage (4 ± 1 °C) were investigated. The fillets were analyzed for sensory scores, total volatile basic nitrogen (TVB-N), ATP-related compounds (ATP, IMP, HxR, and Hx), K value, and biogenic amines (BAs). The results proved that VP inhibited the increase of microorganisms, TVB-N, Hx, and putrescine in silver carp, and slowed the reduction in sensory score. Therefore, VP can be applied for preservation of the silver carp fillets to improve its quality. For identification, 16S rRNA genes of the isolated pure strains were sequenced and analyzed. On the initial day of storage, Chryseobacterium was the dominant bacterial genus. At the end of shelf life, Pseudomonas was the most common group in AP fillets and Aeromonas followed by Yersinia were found mainly in VP samples. Practical applications Silver carp (Hypophthalmichthys molitrix) are distributed widely in fresh water systems. The world aquaculture production of silver carp was 4,354,638 tons, and it ranked second highest among freshwater fish species in 2015, but they are perishable during storage because of microbial spoilage and biochemical reactions. Vacuum packaging (VP) has proved to be effective for extending the shelf-life of aquatic products by excluding oxygen that prevents the growth of spoilage bacterial. However, little information is available on the microbial succession of VP silver carp. Therefore, this work was to determine the differences of microbiological succession on chilled silver carp fillets under air-packed (AP) and VP conditions using a combination of culture-based and 16S rRNA gene analysis methods. Furthermore, this study will give valuable information about development and spoilage of VP silver carp fillets.

Clinical outcomes of linezolid and vancomycin in patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus stratified by baseline renal function: a retrospective, cohort analysis

BackgroundThe primary objective of this study is to assess whether baseline renal function impacts treatment outcomes of linezolid and vancomycin (with a dose-optimized regimen) for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia.MethodsWe conducted a retrospective cohort analysis of data generated from a prospective, randomized, controlled clinical trial (NCT 00084266). The analysis included 405 patients with culture-proven MRSA pneumonia. Baseline renal function was stratified based on creatinine clearance.Clinical and microbiological success rates and presence of nephrotoxicity were assessed at the end of treatment (EOT) and end of study (EOS). Multivariate logistic regression analyses of baseline patient characteristics, including treatment, were performed to identify independent predictors of efficacy. Vancomycin concentrations were analyzed using a nonlinear mixed-effects modeling approach. The relationships between vancomycin exposures, pharmacokinetic-pharmacodynamic index (trough concentration, area under the curve over a 24-h interval [AUC0–24], and AUC0–24/MIC) and efficacy/nephrotoxicity were assessed in MRSA pneumonia patients using univariate logistic regression or Cox proportional hazards regression analysis approach.ResultsAfter controlling for use of vasoactive agents, choice of antibiotic therapy and bacteremia, baseline renal function was not correlated with clinical and microbiological successes in MRSA pneumonia at either end of treatment or at end of study for both treatment groups. No positive association was identified between vancomycin exposures and efficacy in these patients. Higher vancomycin exposures were correlated with an increased risk of nephrotoxicity (e.g., hazards ratio [95% confidence interval] for a 5 μg/ml increase in trough concentration: 1.42 [1.10, 1.82]).ConclusionsIn non-dialysis patients, baseline renal function did not impact the differences in efficacy or nephrotoxicity with treatment of linezolid versus vancomycin in MRSA pneumonia.

Conventional Versus Prolonged Infusion of Meropenem in Neonates With Gram-negative Late-onset Sepsis: A Randomized Controlled Trial.

Gram-negative bacteria are associated with significant morbidity and mortality in preterm and term newborns. Meropenem has widespread efficacy and often allows for monotherapy in this group. Prolonged infusion instead of infusion over 30 minutes has been suggested to result in higher microbiologic efficacy. To compare the clinical and microbiologic efficacy and safety of prolonged infusions versus conventional dosing of meropenem in neonates with Gram-negative late-onset sepsis (GN-LOS). A prospective, randomized clinical trial was conducted in neonates with GN-LOS admitted to neonatal intensive care unit (NICU), Mansoura University Children's Hospital, between August 2013 and June 2015. Patients were randomly assigned to receive either intravenous infusion of meropenem over 4 hours (infusion group) or 30 minutes (conventional group) at a dosing regimen of 20 mg/kg/dose every 8 hours and 40 mg/kg/dose every 8 hours in meningitis and Pseudomonas infection. Clinical and microbiologic success in eradication of infection were the primary outcomes. Neonatal mortality, meropenem-related (MR) duration of mechanical ventilation, MR length of NICU stay, total length of NICU stay, duration of respiratory support (RS), duration of mechanical ventilation, MR duration of inotropes and adverse effects were secondary outcomes. A total of 102 infants (51 in each group) were recruited. The infusion group demonstrated a significantly higher rate of clinical improvement and microbiologic eradication 7 days after starting meropenem therapy compared with the conventional group. Mortality and duration of RS were significantly less in the infusion group compared with conventional group. Acute kidney injury after meropenem treatment was significantly less in the infusion group compared with the conventional group. Prolonged infusion of meropenem in neonates with GN-LOS is associated with higher clinical improvement, microbiologic eradication, less neonatal mortality, shorter duration of RS and less acute kidney injury compared with the conventional strategy.

Prescription Patterns for Tigecycline in Severely Ill Patients for Non-FDA Approved Indications in a Developing Country: A Compromised Outcome.

Introduction: With the rise in antibiotic resistance, tigecycline has been used frequently in off-label indications, based on its in-vitro activity against multidrug-resistant organisms. In this study, our aim was to assess its use in approved and unapproved indications.Materials and Methods: This is a retrospective chart review evaluating a 2-year experience of tigecycline use for > 72 h in 153 adult patients inside and outside critical care unit from January 2012 to December 2013 in a Lebanese tertiary-care hospital.Results: Tigecycline was mostly used in off-label indications (81%) and prescribed inside the critical care area, where the number of tigecycline cycles was 16/1,000 patient days. Clinical success was achieved in 43.4% of the patients. In the critically ill group, it was significantly higher in patients with a SOFA score <7 using multivariate analysis (Odds Ratio (OR) = 12.51 [4.29–36.51], P < 0.0001). Microbiological success was achieved in 43.3% of patients. Yet, the univariate and adjusted multivariate models failed to show a significant difference in this outcome between patients inside vs. outside critical care area, those with SOFA score <7 vs. ≥ 7, and in FDA-approved vs. off-label indications. Total mortality reached ~45%. It was significantly higher in critically ill patients with SOFA score ≥7 (OR = 5.17 [2.43–11.01], P < 0.0001) and in off-label indications (OR = 4.00 [1.30–12.31], P = 0.01) using an adjusted multivariate model. Gram-negative bacteria represented the majority of the clinical isolates (81%) and Acinetobacter baumannii predominated (28%). Carbapenem resistance was present in 85% of the recovered Acinetobacter, yet, more than two third of the carbapenem-resistant Acinetobacter species were still susceptible to tigecycline.Conclusion: In our series, tigecycline has been mostly used in off-label indications, specifically in severely ill patients. The outcome of such infections was not inferior to that of FDA-approved indications, especially inside critical care area. The use of this last resort antibiotic in complicated clinical scenarios with baseline microbiological epidemiology predominated by extensively-drug resistant pathogens ought to be organized.

Double-carbapenem combination as salvage therapy for untreatable infections by KPC-2-producing Klebsiella pneumoniae.

We report our experience using the double-carbapenem combination as salvage therapy for patients with untreatable infections caused by KPC-2- producing Klebsiella pneumoniae. A total of 27 patients in two institutions in Athens, Greece suffering from complicated urinary tract infections (16) with or without secondary bacteraemia (four and 12 respectively), primary (six) or catheter-related bloodstream infections (two), HAP or VAP (two) and external ventricular drainage infection (one) were treated exclusively with ertapenem and high-dose prolonged infusion meropenem because in-vitro active antimicrobials were unavailable (19) or failed (four) or were contraindicated (six). Most patients presented with severe infections with median APACHE II score of 17 and 11 of those patients (40.7%) had severe sepsis (five) or septic shock (six). The clinical and microbiological success was 77.8 and 74.1% respectively. Crude mortality was 29.6% with attributable mortality of 11.1%. Adverse events, none of them severe, were reported in four patients (14.8%). The double-carbapenem combination as an exclusive regimen represents a safe and valid salvage therapy for untreatable infections by extensively- or pandrug-resistant KPC-producing K.pneumoniae.

Is the growth of microorganisms limited by carbon availability during chalcopyrite bioleaching?

Microorganisms, which play a key role during mineral dissolution in bioleaching processes, require O2 to promote the oxidation processes of sulfide mineral dissolution and CO2 or more complex molecules as carbon source for cell growth. Preliminary models have been proposed for relating the microbial succession in bioleaching heaps with the activity of different CO2 fixation pathways. The increase of internal heap temperature during bioleaching improves the rate of chalcopyrite dissolution. However, it also negatively affects CO2 and O2 availability, consequently the microbial community changes and only the best adapted microorganisms are capable of growing under the limiting conditions. In this work we attempt to elucidate how microbiological succession proceeds in a semi-industrial bioleaching column test system, with emphasis in determining the identity of the microorganisms participating and the metabolic dynamics of carbon fixation pathways. In silico reconstruction of the carbon fixation metabolisms based on available genomes and the gene expression studies using microarray and RNA-seq were performed. The physicochemical conditions and the metallurgical parameters were also included in the analysis. Although the investigation is based on a non-homogeneous system - which leads to some seemingly contradictory data - the results showed a clear change in the structure of the microbial community as well as in the expression of pathways for CO2 fixation, as the column test progressed. These changes were directly related to two factors, the temperature inside column and the CO2 availability. The gene expression analyses confirmed the temporal distribution of microorganisms as a function of the temperature and the different pathways for CO2 fixation. The evidences obtained here support the fact that low CO2 availability becomes an important asset to the microbial population survival and growth promotion in the bioleaching environments. The determination of the expression level of the key genes is a good opportunity to improve a sound understanding of the high temperature bio-assisted heap leaching of chalcopyrite and to optimize the technology.

The effect of diabetes mellitus on outcomes of patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus: data from a prospective double-blind clinical trial comparing treatment with linezolid versus vancomycin.

BackgroundThe presence of diabetes mellitus increases the risk of several severe infections, but data on its effect on treatment outcomes in patients with nosocomial pneumonia (NP) caused by methicillin-resistant Staphylococcus aureus (MRSA) are limited.MethodsWe retrospectively analyzed data from a double-blind, randomized, multi-center, international clinical trial of culture-confirmed MRSA NP that compared treatment with linezolid to vancomycin. Specifically, we evaluated the clinical and microbiologic outcomes of patients with and without diabetes in the modified intent to treat population at end-of-treatment (EOT) and end-of-study (EOS, 7–30 days post-EOT).ResultsAmong 448 enrolled patients 183 (40.8 %) had diabetes mellitus, 87 (47.5 %) of whom received linezolid and 96 (52.5 %) vancomycin. Baseline demographic and clinical characteristics were similar for the two treatment groups. Clinical success rates at EOS were 57.6 % with linezolid and 39.3 % with vancomycin, while microbiological success rates were 58.9 % with linezolid and 41.1 % with vancomycin. Among diabetic patients, rates of mortality and study drug-related adverse effects were similar between the treatment groups. Overall day 28 mortality rates were higher among diabetic patients compared to non-diabetic patients (23.5 vs 14.7 %, respectively: RD = 8.8 %, 95 % CI [1.4, 16.3]).ConclusionsAmong diabetic patients with MRSA NP, treatment with linezolid, compared to vancomycin, was associated with higher clinical and microbiologic success rates, and comparable adverse event rates.Trial registrationNCT00084266.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1779-5) contains supplementary material, which is available to authorized users.

Clinical efficacy and safety of vancomycin compared with linezolid for the treatment of neonatal gram-positive bacterial sepsis

To evaluate the clinical efficacy and safety of vancomycin and linezolid for the treatment of gram-positive neonatal bacterial sepsis. The data of neonates diagnosed as gram-positive bacterial sepsis in neonatology department of Suzhou Municipal Hospital from June 2009 to December 2015 were retrospectively collected. These neonates were divided into vancomycin group and linezolid group. Propensity score matching (PSM) on baseline variables was used to balance the two groups by identifying a comparable group of neonates who received vancomycin and linezolid therapy. Clinical and microbiologic success rates were compared by chi-square test, and changes of laboratory parameters before and after treatment at the end of treatment were then directly compared by rank-sum test between the matched groups. In vancomycin group, correlation between trough concentration of vancomycin and clinical efficacy were evaluated. Totally 108 and 209 cases were respectively selected in vancomycin and linezolid groups; 108 cases with well-matched baseline characteristics were included in matched linezolid group. The clinical success rates of vancomycin vs. linezolid therapy were 86.1%(93/108) and 88.9%(96/108)(P=0.681), and the microbiologic success rates were 91.7%(99/108) and 93.5%(101/108)(P=0.795). The average trough concentration of vancomycin was (12±8) mg/L. The rate of reaching the high trough concentration standard was only 33.3%(36/108). In 50 (46.3%) cases the dose was adjusted according to the initial concentration data. Compared to less than 10 mg/L, the clinical efficacy of trough concentration in 10-20 mg/L was much higher(93.9%(46/49) vs. 78.6%(33/42), P=0.031). Total bilirubin and platelet count had significant difference between the two-matched groups (34.1(14.9, 91.0)μmol/L vs. 53.0(27.0, 121.6)μmol/L, P=0.034; 301.0(198.8, 416.0)×10(9)/L vs. 195.5(94.0, 283.2)×10(9)/L, P=0.000). The incidence of linezolid related thrombocytopenia was 13.4%(28 cases). The clinical effect of vancomycin and linezolid on gram-positive bacterial sepsis in neonates is comparable. The rate of trough concentration of vancomycin reaching the high trough concentration standard is low, and the clinical efficacy is related to trough concentration. Linezolid have an effect on bilirubin and platelet count, the risk of thrombocytopenia should be monitored closely during linezolid treatment.

Empirical monotherapy with meropenem or combination therapy: the microbiological point of view.

The increase in the number of clinical isolates of multiresistant Enterobacteriaceae and Pseudomonas aeruginosa raises problems in decision-making on empirical treatments for severe Gram-negative bacilli-associated infections. The aim of our study is to determine the resistance of meropenem in our setting and the co-resistance of a combination of this compound with two antibiotics from different families: amikacin and ciprofloxacin. Between 2009 and 2013, a total of 81,310 clinical isolates belonging to the main species of Enterobacteriaceae and 39,191 clinical isolates of P. aeruginosa isolated in 28 hospitals in the Valencian Community on the South East Mediterranean Coast of Spain were analyzed using data provided by RedMiva (microbiological surveillance network of the Valencian Community). Meropenem resistance in Enterobacteriaceae increased from 0.16% in 2009 to 1.25% in 2013. Very few Enterobacteriaceae strains resistant to meropenem were sensitive to ciprofloxacin; in contrast, the combination of meropenem and amikacin led to a marked decrease in the risk of the microorganisms being resistant to both drugs (RR = 34 in 2013). In the case of P. aeruginosa, meropenem resistance also increased (from 14.32% in 2009 to 24.52% in 2013). Most meropenem-resistant P. aeruginosa isolates were also resistant to fluoroquinolones. However, the addition of amikacin led to a more than three-fold decrease in the risk of resistance. In our setting, empirical treatment with meropenem is adequate in enterobacterial infections, but poses difficulties when infection due to P. aeruginosa is suspected, in which case a combination of meropenem and amikacin has been shown to have a higher microbiological success rate.

Use of Ertapenem at an Academic Medical Center

Background Ertapenem is a once-daily, broad-spectrum antibiotic convenient for outpatient parenteral antimicrobial therapy (OPAT). The primary focus of our study was to assess the efficacy and safety of ertapenem for OPAT. Methods Data were retrospectively collected from patients receiving ertapenem for a 24-month period. Patient characteristics, therapeutic indication, and microbiology were reviewed. Outcome measures included clinical and microbiologic success, improvement, or failure and the safety profile of ertapenem. Results Two hundred ninety-two consecutive patients received ertapenem, and 202 met inclusion criteria for ertapenem OPAT. Patients received a median of 29 days for a range of indications, most commonly intra-abdominal (32.2%), osteomyelitis (29.2%), and skin and soft tissue infection (14.4%). One hundred seventeen OPAT patients had a polymicrobial infection. One hundred eighty-six patients were evaluable for clinical outcomes. Clinical success occurred in 92% of patients: clinical improvement was achieved in 69%, and clinical cure was achieved in 23% of patients. Clinical failure occurred in 15 patients (8.1%). Ertapenem was well tolerated with only 25 (13.4%) of 186 patients experiencing an adverse event. The most common adverse drug events were altered mental status in 7 patients and 2 additional patients with seizures in patients with creatinine clearances of less than 50 mL/min, and increased liver function tests (n = 4). Conclusions Ertapenem is frequently used for OPAT because it is convenient, well tolerated, and clinically effective for abdominal, skin and soft tissue, and bone infections. It has an excellent safety profile, but central nervous system irritability in patients with diminished renal function may warrant closer attention.

Evaluation of Vancomycin Use in Late-Onset Neonatal Sepsis Using the Area Under the Concentration-Time Curve to the Minimum Inhibitory Concentration ≥400 Target.

To develop a vancomycin population pharmacokinetic model and assess the probability of attaining a pharmacodynamic target associated with clinical and microbiological success, a ratio of the 24-hour area under the concentration-time curve to the minimum inhibitory concentration (MIC) ≥ 400, in a 5-year clinical cohort of preterm and term neonatal patients with late-onset staphylococcal sepsis. Therapeutic drug monitoring data were obtained from septic neonates with ≥1 vancomycin concentration(s) from January 2006 to September 2011. Only neonates with a postnatal age of >72 hours and a positive microbiological culture were included. Population pharmacokinetic model was developed using nonlinear mixed effects modeling (NONMEM 7.2). Eleven demographic characteristics were evaluated as covariates. Probabilities of achieving the pharmacodynamic target were evaluated. A 1-compartment model with first-order elimination was constructed from 528 vancomycin concentrations collected from 152 preterm and term neonates. Body weight, creatinine clearance (CL), and postmenstrual age were identified as significant covariates. Estimated vancomycin CL and volume of distribution for typical neonates were 0.068 ± 0.03 L·h·kg and 0.62 ± 0.13 L/kg, respectively. Coagulase-negative staphylococci (85.5%) and Staphylococcus aureus (14.5%) were the common pathogenic organisms. The distribution of vancomycin MIC breakpoints was composed of approximately 70% MIC breakpoint of ≤2 mcg/mL. Approximately 54% of neonates, with a median serum creatinine concentration of 0.44 mg/dL, achieved the target ratio of 24-hour area under the concentration-time curve to the MIC ≥ 400 with a median daily dose of 30 (interquartile range, 21-42) mg/kg. Body weight, creatinine CL, and postmenstrual age significantly influenced vancomycin CL. The current vancomycin doses are acceptable at MICs ≤1 mcg/mL because they are likely to achieve the pharmacodynamic target in the majority of neonatal patients, although higher doses may be considered for more resistant staphylococcal infections.

Clinical and economic impact of appropriate empirical antibiotic therapy in complicated intra-abdominal infections: A retrospective study

AimsTo study the comparative efficacy of Piperacillin/Tazobactam (PIP-TAZ) and new fixed dose combination (FDC) of ceftriaxone+sulbactam+ethylenediaminetetraacetic acid (EDTA) in treatment of intra-abdominal infections (IAIs) and to analyze the cost expenditures with these therapies. MethodsCase sheets of patients treated for IAI with either of PIP-TAZ or FDC were analyzed. Demographic characteristics, surgical procedure, antibiotic therapy and length of hospital stay were recorded and the cost of total hospital care was analyzed. Efficacy was measured in terms of microbiological and clinical successes. ResultsOut of 120 patients identified as culture positive, empirical PIP-TAZ was given in 58 patients, of whom 39 (67.24%) patients achieved clinical success. The remaining achieved success with either meropenem or meropenem+colistin combination. Out of 62 FDC treated patients, 54 (87.09%) achieved clinical success and the remaining patients were cured with FDC+colistin combination therapy. The clinical success rates in culture negative patients treated with FDC and PIP-TAZ were 87.5% and 21.42% respectively. Comparative cost expenditure analysis of the two treatment groups revealed that the overall treatment cost for successful patients treated with FDC was 36.72% lesser than that of PIP-TAZ treated groups. Similarly, the failed patient group also resulted in 35.44% higher expenditure in PIP-TAZ group than in FDC group. ConclusionThe study reveals the superior efficacy of FDC over PIP-TAZ treatment in IAIs which has a direct impact on the cost of treatment. The comparative pharmacoeconomic analysis shows that the selection of FDC over PIP-TAZ reduces up to 35% costs involved in IAIs treatments.

Ertapenem-Containing Double-Carbapenem Therapy for Treatment of Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae.

We describe outcomes of patients with infections with carbapenem-resistant Klebsiella pneumoniae (CRKP) who received ertapenem-containing double-carbapenem therapy (ECDCT). Clinical success was observed in 7/18 (39%) patients overall: bloodstream infections, 3/7 (43%); pneumonia, 1/5 (20%); intraabdominal infections, 0/2 (0%); urinary tract infections, 2/3 (67%); and a skin and skin structure infection, 1/1 (100%). Microbiologic success was observed in 11/14 (79%) evaluable patients; 5/18 (28%) patients died. ECDCT may be effective for CRKP infections with limited treatment options.