Novel Antibiotics Targeting Respiratory ATP Synthesis in Gram-positive Pathogenic Bacteria.

Antimicrob Agents Chemother. 2012 May 21;

Authors: Balemans W, Vranckx L, Lounis N, Pop O, Guillemont J, Vergauwen K, Mol S, Gilissen R, Motte M, Lançois D, De Bolle M, Bonroy K, Lill H, Andries K, Bald D, Koul A

Abstract
Emergence of drug-resistant bacteria represents a high, unmet medical need and discovery of new antibacterials acting on new bacterial targets is strongly needed. ATP synthase has been validated as antibacterial target in Mycobacterium tuberculosis, where its activity can be specifically blocked by the diarylquinoline TMC207. However, potency of TMC207 is restricted to mycobacteria with little or no effect on the growth of other Gram-positive or on Gram-negative bacteria. Here, we identify diarylquinolines with activity against key Gram-positive pathogens, significantly extending the antibacterial spectrum of the diarylquinoline class of drugs. These compounds inhibited growth of Staphylococcus aureus in planktonic state as well as in metabolically resting bacteria grown in a biofilm culture. Furthermore, time-kill experiments showed that the selected hits are rapidly bactericidal. Drug-resistant mutations were mapped to the ATP synthase enzyme, and biochemical analysis as well as drug-target interaction studies reveal ATP synthase as a target for these compounds. Moreover, knockdown of the ATP synthase expression strongly suppressed growth of S. aureus, revealing a crucial role of this target in bacterial growth and metabolism. Our data represent a proof-of-principle for using the diarylquinoline class of antibacterials in key Gram-positve pathogens. Our results suggest that broadening the antibacterial spectrum for this chemical class is possible without drifting off from the target. Development of the diarylquinolines class may represent a promising strategy for combating Gram-positive pathogens.

PMID: 22615276 [PubMed - as supplied by publisher]

Impact of cefepime therapy on mortality among patients with blood stream infections caused by extended spectrum ?-lactamase-producing Klebsiella pneumoniae and Escherichia coli.

Antimicrob Agents Chemother. 2012 Apr 30;

Authors: Chopra T, Marchaim D, Veltman J, Johnson P, Zhao JJ, Tansek R, Hatahet D, Chaudhry K, Pogue JM, Rahbar H, Chen TY, Truong T, Rodriguez V, Ellsworth J, Bernabela L, Bhargava A, Yousuf A, Alangaden G, Kaye KS

Abstract
Background: Extended-spectrum beta lactamase (ESBL)-producing pathogens are associated with extensive morbidity, mortality, and rising healthcare costs. Scant data exist on the impact of antimicrobial therapy on clinical outcomes in patients with ESBL bloodstream infections (BSI) and no large studies have examined the impact of cefepime therapy. Methods: A retrospective 3 year study was performed at the Detroit Medical Center on adult patients with ESBL-producing K. pneumoniae or E. coli BSI. Data were collected from the medical records of study patients at five hospitals between January 2005 and December 2007. Multivariate analysis was performed using logistic regression. Results: One-hundred and forty-five patients with BSI due to ESBL-producing pathogens were studied, including K. pneumoniae (83%), and E. coli(16.5%). The mean age of the patients was 66 years, 51% were female and 79.3% were African-American. 53 patients (37%) died in the hospital and 92 survived to discharge. In bivariate analysis, the following variables were associated with mortality (p<0.05): presence of a rapidly fatal condition at the time of admission, use of gentamicin as a consolidative therapeutic agent, and presence of one or more of the following prior to culture date: mechanical ventilation, stay in the intensive care unit (ICU), and presence of a central venous catheter. In multivariate analysis, the predictors of in-hospital mortality included: intensive care unit stay (OR=2.17, 95% CI 0.98-4.78), presence of a central line prior to positive culture (OR=2.33, 95%CI 0.77-7.03) presence of a rapidly fatal condition at the time of admission (OR=5.13,95%CI 2.13-12.39) and recent prior hospitalization (OR=1.92,95%CI 0.83-4.09). When carbapenems were added as empiric therapy to the predictor model, there was a trend between empiric carbapenem therapy and decreased mortality (OR=0.61,95% CI 0.26-1.50). When added to the model, receipt of empiric cefepime alone (n=43) was associated with increased mortality, although this association did not reach statistical significance (OR= 1.66, 95% CI 0.71-3.87). Median length of hospital stay was shorter for patients receiving empiric cefepime and longer for those receiving empiric or consolidated carbapenem therapy. Conclusions: In multivariate analysis, empiric therapy with cefepime for BSI due to an ESBL-producing pathogen was associated with a trend towards an increased mortality risk and empiric carbapenem therapy was associated with a trend towards decreased mortality risk.

PMID: 22547616 [PubMed - as supplied by publisher]

Summary of the Contemporary (2010) Ceftaroline Activity Among USA Pathogens: Report from the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) Surveillance Program.

Antimicrob Agents Chemother. 2012 Apr 2;

Authors: Flamm RK, Sader HS, Farrell DJ, Jones RN

Abstract
The Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) Surveillance Program is a sentinel resistance monitoring system designed to track the activity of ceftaroline and comparator agents. In the United States (USA) a total of 8,434 isolates were collected during the 2010 surveillance program from 65 medical centers distributed across the nine Census Regions (5 to 10 medical centers per region). All organisms were isolated from documented infections including 3,055 (36.2%) bloodstream infections, 2,282 (27.1%) respiratory tract infections, 1,965 (23.3%) acute bacterial skin and skin structure infections, 665 (7.9%) urinary tract infections, and 467 (5.5%) miscellaneous other infection sites. Ceftaroline was the most potent ?-lactam agent tested against staphylococci. The MIC(90) values were 1 ?g/ml for methicillin-resistant Staphylococcus aureus (MRSA; 98.4% susceptible) and 0.5 ?g/ml for methicillin-resistant coagulase-negative staphylococci (CoNS). Ceftaroline was 16- to 32-fold more potent than ceftriaxone against methicillin-susceptible staphylococcal strains. All staphylococcus isolates (S. aureus and CoNS) were inhibited at ceftaroline MIC values of ?2 ?g/ml. Ceftaroline also displayed potent activity against streptococci (MIC(90,) 0.015 ?g/ml for ?-hemolytic streptococci; MIC(90,) 0.25 ?g/ml for penicillin-resistant Streptococcus pneumoniae). Potent activity was also shown against the gram-negative pathogens (Haemophilus influenzae, Haemophilus parainfluenzae and Moraxella catarrhalis). Furthermore, wild type strains of Enterobacteriaceae (non-ESBL-producing strains and non-AmpC-hyperproducing strains) were often susceptible to ceftaroline. Continued monitoring through surveillance networks will allow for the assessment of the evolution of resistance as this new cephalosporin is used more broadly to provide clinicians with up-to-date information to assist in antibiotic stewardship and therapeutic decision making.

PMID: 22470115 [PubMed - as supplied by publisher]

Carbapenem Therapy for Bacteremia due to Extended-spectrum ?-lactamase-producing Escherichia coli or Klebsiella pneumoniae: Implications of Ertapenem Susceptibility.

Antimicrob Agents Chemother. 2012 Mar 19;

Authors: Lee NY, Lee CC, Huang WH, Tsui KC, Hsueh PR, Ko WC

Abstract
A retrospective study was conducted at two medical centers in Taiwan to evaluate clinical characteristics, outcome, and risk factors of mortality among patients treated with a carbapenem for bacteremia caused by extended-spectrum beta-lactamase (ESBL)-producing organisms. A total of 251 patients with bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae treated by a carbapenem were identified. Among these ESBL-producing isolates, susceptibility rates of ertapenem (MICs ?0.25 ?g/ml) were 83.8% and 76.4%, meropenem 100% and 99.3%, and imipenem 100% and 97.9%, respectively. There were no significant differences in the critical illness (P=0.1) or sepsis-related mortality rate (P=0.2) among bacteremia caused by ESBL-producing K. pneumoniae (140 isolates, 55.8%) and E. coli (111, 44.2%) isolates. Multivariate analysis of variables related to sepsis-related mortality revealed that the presence of severe sepsis (odds ratio [OR], 15.9; 95% confidence interval [CI], 5.84-43.34; P<0.001), hospital-onset bacteremia (OR, 4.65; 95% CI, 1.42-15.24; P=0.01), and ertapenem-nonsusceptible isolates (OR, 5.12; 95% CI, 2.04-12.88; P=0.001) were independent risk factors. The patients receiving inappropriate therapy had a higher sepsis-related mortality than those with appropriate therapy (P=0.002), irrespective of ertapenem, imipenem, or meropenem therapy. Infections due to the ertapenem-susceptible isolates (MICs ?0.25 ?g/ml) were associated with a more favorable outcome than those due to ertapenem-nonsusceptible isolates (MICs >0.25 ?g/ml), if treated by a carbapenem. However, the mortality of bacteremic episodes due to isolates with MICs ?0.5 ?g/ml was similar to those with MICs >0.5 ?g/ml (P=0.8). Such a finding supports the rationale of the current CLSI-2011 criteria of carbapenems for Enterobacteriaceae.

PMID: 22430969 [PubMed - as supplied by publisher]

Activity of Oxacillin versus Vancomycin against Oxacillin-Susceptible mecA-Positive Staphylococcus aureus Clinical Isolates by Population Analyses, Time-Kill Assays and a Murine Thigh Infection Model.

Antimicrob Agents Chemother. 2012 Mar 19;

Authors: Labrou M, Michail G, Ntokou E, Pittaras TE, Pournaras S, Tsakris A

Abstract
We tested the activity of oxacillin compared with vancomycin, against 15 oxacillin-susceptible MRSA clinical isolates (OS-MRSA). By population analyses 6 OS-MRSA grew up to 8 ?g/ml and 9 isolates 12 to >32 ?g/ml dicloxacillin and all isolates up to 2 ?g/ml vancomycin. Both drugs exhibited similar bactericidal activity. In experimental infections, the therapeutic efficacy of dicloxacillin was significant (P <0.05 vs. untreated controls) in 10 OS-MRSA and vancomycin was effective (P <0.05) against 12 isolates; dicloxacillin had comparable efficacy with vancomycin (P >0.05) in 8 isolates. The favorable response to dicloxacillin treatment might suggest anti-staphylococcal penicillins against OS-MRSA infections.

PMID: 22430957 [PubMed - as supplied by publisher]

Empirical Use of Ciprofloxacin for Acute Uncomplicated Pyelonephritis Caused by Escherichia coli in Communities Where the Prevalence of Fluoroquinolone Resistance is High.

Antimicrob Agents Chemother. 2012 Mar 5;

Authors: Jeon JH, Kim K, Han WD, Song SH, Park KU, Rhee JE, Song KH, Park WB, Kim ES, Park SW, Kim NJ, Oh MD, Kim HB

Abstract
There is little information about the effectiveness of ciprofloxacin in regions where ciprofloxacin-resistant Escherichia coli is prevalent. This study was conducted to evaluate whether ciprofloxacin is effective as initial empirical antibiotic for treatment of uncomplicated acute pyelonephritis (APN) due to ciprofloxacin-resistant E. coli. A total of 255 women with clinical diagnoses of uncomplicated APN due to E. coli were enrolled in the emergency department between March 2005 and December 2008. All enrolled patients were initially treated with ciprofloxacin. Patients were followed up 4 to 7 days after the start of therapy and 14 to 21 days after its completion. At the first follow-up visit, ciprofloxacin was changed to the appropriate antibiotic where necessary depending on the antibiotic susceptibility results. Not only improvement of symptoms and signs but also microbiologic eradication was assessed at each visit. Fifteen percent (39/255) of the E. coli isolates were resistant to ciprofloxacin. There was no statistically significant difference in clinical cure rate between the ciprofloxacin-susceptible group and the ciprofloxacin-resistant group at first follow-up (87.0% versus 76.9%, p = 0.135) or second follow-up (98.6% versus 94.9%, p = 0.177). However there was a lower microbiologic cure rate in the ciprofloxacin-resistant group than in the ciprofloxacin-susceptible group (92.4% versus 41.7%, p = 0.000) at first follow-up visit. No complications occurred in the ciprofloxacin-resistant group during the follow-up period. Our findings indicate that ciprofloxacin is an appropriate choice for empirical therapy of uncomplicated APN, and has no serious adverse outcomes, if it is tailored appropriately, even in women infected with ciprofloxacin-resistant E. coli.

PMID: 22391544 [PubMed - as supplied by publisher]

Microbiological Analysis of a Prospective, Randomized, Double-Blind Trial Comparing Moxifloxacin and Clindamycin in the Treatment of Odontogenic Infiltrates and Abscesses (MOCLI Study).

Antimicrob Agents Chemother. 2012 Feb 21;

Authors: Sobottka I, Wegscheider K, Balzer L, Böger RH, Hallier O, Giersdorf I, Streichert T, Haddad M, Platzer U, Cachovan G

Abstract
The objective of this study was to identify the oral pathogens found in odontogenic infections, to determine their susceptibility to amoxicillin/clavulanic acid (AMC), clindamycin (CLI), doxycycline (DOX), levofloxacin (LVX), moxifloxacin (MXF), and penicillin (PEN), and to search for an association between specific pathogens and type of infection.Swabs from patients enrolled in a randomized, double-blind phase II trial comparing MXF and CLI in the treatment of odontogenic abscesses or inflammatory infiltrates were cultured on media for aerobes and anaerobes. All bacterial isolates were identified at the species level.Overall, 205 isolates were cultured from 71 patients: 77 viridans streptococci, 56 Prevotella spp., 19 Neisseria spp., 17 Streptococcus (S.) anginosus group and hemolytic streptococci, 15 other anaerobes, and 21 other bacteria. 98% of pathogens were susceptible to MXF, 96% to AMC, 85% to LVX, 67% to PEN, 60% to CLI, and 50% to DOX. S. anginosus group and hemolytic streptococci were found significantly more frequent (p=0.04) in patients with abscesses (12/95) than in patients with infiltrates (5/110). In four patients of the infiltrate group who failed to respond to CLI therapy, three isolates of S. mitis group and four Neisseria spp. resistant to CLI were found.In this study S. anginosus group and hemolytic streptococci were clearly associated with odontogenic abscesses. Our analysis suggests that viridans streptococci and Neisseria spp. have a decisive role in the etiology of odontogenic infiltrates. MXF's high in vitro activity against odontogenic bacteria corresponds well to its clinical results in the treatment of odontogenic abscesses and infiltrates.

PMID: 22354306 [PubMed - as supplied by publisher]

Evaluation of Ceftaroline (CPT) Activity versus Ceftriaxone (CRO) Against Clinical Isolates of Streptococcus pneumoniae with Varying Susceptibilities to Cephalosporins in an in-vitro Pharmacokinetic/Pharmacodynamic (PK/PD) Model.

Antimicrob Agents Chemother. 2012 Feb 21;

Authors: Steed ME, Vidaillac C, Winterfield P, Biek D, Rybak MJ

Abstract
Drug resistance in Streptococcus pneumoniae, a frequent pathogen in community-acquired pneumonia, is increasing. Ceftaroline (active metabolite of ceftaroline fosamil) is a broad-spectrum intravenous cephalosporin with activity in vitro against drug resistant Gram-positive organisms. We investigated ceftaroline 600 mg q 12 h (fCmax=15.2 ?g/mL, T(1/2)=2.5 h) vs. ceftriaxone 1 g q 24 h (fCmax=23 ?g/mL, T(1/2)=8 h) against six clinical S. pneumoniae isolates in an one-compartment in vitro PK/PD 96 h model (starting inoculum of 10(7) CFU/mL). Differences in CFU/mL (at 24-96 h) were evaluated by ANOVA with a Tukey's Post-Hoc test. Bactericidal activity was defined as a ? 3-log(10) CFU/mL decrease from the initial inoculum. Ceftaroline MICs were 0.06, 0.015, ? 0.008, 0.25, 0.25, and 0.5 ?g/mL and ceftriaxone MICs were 0.5, 0.25, 0.25, 4, 4, and 8 ?g/mL for SP 1477, SP 669, SP 132, SP 211, SP 90, and SP 1466, respectively. Against the ceftaroline and ceftriaxone susceptible strain SP 1477, ceftaroline displayed sustained bactericidal activity (3 - 96 h, - 6.48 log(10) CFU/mL) and was significantly (p ? 0.012) better than ceftriaxone (72-96 h, -2.03 log(10) CFU/mL). Against the ceftriaxone resistant strains, ceftaroline displayed sustained bactericidal activity at 96 h and was significantly better than ceftriaxone [SP211 (-5.91 log(10) CFU/mL, p ? 0.002), SP 90 (-5.26 log(10) CFU/mL, p ? 0.008), and SP1466 (-5.14 log(10) CFU/mL, p ? 0.042).] Ceftaroline was the most effective drug and displayed sustained bactericidal activity. Ceftaroline fosamil may provide a therapeutic option to treat ceftriaxone resistant S. pneumoniae infections.

PMID: 22354289 [PubMed - as supplied by publisher]

Comparison of the clinical characteristics and outcomes associated with vancomycin-resistant Enterococcus faecalis and vancomycin-resistant E. faecium bacteremia.

Antimicrob Agents Chemother. 2012 Feb 21;

Authors: Hayakawa K, Marchaim D, Martin ET, Tiwari N, Yousuf A, Sunkara B, Pulluru H, Kotra H, Hasan A, Bheemreddy S, Sheth P, Lee D, Kamatam S, Bathina P, Nanjireddy P, Chalana IK, Patel S, Kumar S, Vahia A, Ku K, Yee V, Swan J, Pogue JM, Lephart PR, Rybak MJ, Kaye KS

Abstract
Background: Published patient cohorts with bacteremia due to vancomycin-resistant Enterococcus (VRE) have predominantly consisted of E. faecium. Little is known about the epidemiology and outcomes associated with bacteremia due to VR E. faecalis.Methods: A retrospective study from 01/2008 to 10/2010 was conducted at Detroit Medical Center (DMC). Unique patients with blood cultures due to VRE were reviewed. Outcomes were analyzed using logistic regression.Results: During the study period, 105 cases of bacteremia due to VR E. faecalis and 197 cases of bacteremia due to VR E. faecium were identified. The mean age of the study cohort was 61.5 ±15 years, 162 (53.6%) were male. After controlling for a propensity score, bacteremia due to VR E. faecalis was associated with greater than two-fold lower in-hospital mortality, compared to bacteremia due to VR E. faecium. Interestingly, bacteremia due to VR E. faecalis was associated with longer length of hospital stay (LOS) after VRE isolation, although total LOS was similar for VR E. faecalis and VR E. faecium.Conclusions: Bacteremia due to VR E. faecalis was associated with a greater than two-fold lower risk for mortality compared to bacteremia due to VR E. faecium, possibly due to the availability of ? -lactam therapeutics for treatment of VR E. faecalis.

PMID: 22354290 [PubMed - as supplied by publisher]

Product Quality of Parenteral Vancomycin Products in the United States.

Antimicrob Agents Chemother. 2012 Feb 6;

Authors: Nambiar S, Madurawe RD, Zuk S, Khan SR, Ellison CD, Faustino PJ, Mans DJ, Trehy ML, Hadwiger ME, Boyne TM, Biswas K, Cox EM

Abstract
Introduction: In response to concerns raised about the quality of parenteral vancomycin products, the U.S. Food and Drug Administration (FDA) is investigating the product quality of all FDA-approved parenteral vancomycin products available in the U.S. Product quality was evaluated independently at two FDA Office of Testing and Research (FDA-OTR) sites. In the next phase of the investigation, being done in collaboration with the National Institute of Allergy and Infectious Diseases, the in vivo activity of these products will be evaluated in an appropriate animal model. This paper summarizes results of the FDA investigation completed thus far.Materials and Methods: One site used a validated Ultra High-Pressure Liquid Chromatography method (OTR-UPLC™) and the second site used the High Performance Liquid Chromatography (HPLC) method for related substances provided in the British Pharmacopeia (BP) monograph for Vancomycin Intravenous Infusion.Results: Similar results were obtained by the two FDA-OTR laboratories using two different analytical methods. The products tested had 90-95% vancomycin B (active component of vancomycin) by the BP-HPLC and 89-94% by OTR-UPLC™ methods respectively. Total impurities were 5-10% by BP-HPLC and 6-11% by OTR-UPLC™ methods. No single impurity was >2.0% and the CDP-1 level was ? 2.0% across all products. Some variability in impurity profiles of the various products was observed.Conclusion: No adverse product quality issues were identified with the six U.S. vancomycin parenteral products. The quality parameters of all parenteral vancomycin products tested surpassed the United States Pharmacopeia acceptance criteria. Additional testing will characterize in vivo performance characteristics of these products.

PMID: 22314525 [PubMed - as supplied by publisher]

Optimal meropenem concentrations to treat multi-drug resistant Pseudomonas aeruginosa septic shock.

Antimicrob Agents Chemother. 2012 Jan 30;

Authors: Taccone FS, Cotton F, Roisin S, Vincent JL, Jacobs F

Abstract
A patient with septic shock due to extensively-drug resistant (XDR) Pseudomonas aeruginosa was cured by optimizing the meropenem (MEM) regimen to obtain at least 40% of the time between two administrations in which drug levels were four times above the minimal inhibitory concentration (MIC) of the pathogen. As standard drug dose did not achieve these optimal concentrations, MEM regimen was progressively increased up to 12g/day (3g q6h in 3-hour extended infusion), which eventually resulted in sepsis resolution. High MEM dosage may represent a valuable therapeutic option for infection due to MDR strains and drug monitoring would allow rapid regimen adjustment in clinical practice.

PMID: 22290984 [PubMed - as supplied by publisher]

The efficacy of ertapenem for treatment of bloodstream infections caused by extended-spectrum ?-lactamase producing Enterobacteriaceae.

Antimicrob Agents Chemother. 2012 Jan 30;

Authors: Collins VL, Marchaim D, Pogue JM, Moshos J, Bheemreddy S, Sunkara B, Shallal A, Chugh N, Eiseler S, Bhargava P, Blunden C, Lephart PR, Memon I, Hayakawa K, Odaliz AL, Chopra T, Munoz-Price S, Carmeli Y, Kaye K

Abstract
Ertapenem is active against ESBLs but inactive against Pseudomonas aeruginosa and Acinetobacter baumannii. Due to lack of therapeutic data for ertapenem in treatment of ESBL bloodstream infections (BSI), group 2 carbapenems (e.g. imipenem or meropenem) are often preferred for treatment of ESBLs, although their anti-pseudomonal activity is unnecessary. From 2005-2010, 261 patients with ESBL BSIs were analyzed. Outcomes were equivalent between patients treated with ertapenem and group 2 carbapenems (mortality rates 6% and 18%, p=0.18).

PMID: 22290982 [PubMed - as supplied by publisher]

Cethromycin versus clarithromycin for community acquired pneumonia: The comparative efficacy and safety outcomes of two double-blinded, randomized, parallel group, multi-center, multi-national non-inferiority studies.

Antimicrob Agents Chemother. 2012 Jan 30;

Authors: English ML, Fredericks CE, Milanesio NA, Rohowsky N, Xu ZQ, Jenta TR, Flavin MT, Eiznhamer DA

Abstract
Community acquired pneumonia (CAP) continues to be a major health challenge in the US and globally. Factors such as overprescribing and non-compliance with antibiotics have added to the growing antibacterial resistance problem. In addition, several agents available for the treatment of CAP have been associated with serious side effects. Cethromycin is a new ketolide antibiotic that may provide prescribing physicians with an additional agent to supplement a continually limited armamentarium. Two global Phase III non-inferiority studies (CL05-001 and CL06-001) to evaluate cethromycin safety and efficacy were designed and conducted in patients with mild-to-moderate CAP. Study CL05-001 demonstrated 83.1% clinical cure rate in cethromycin group compared with 81.1% in clarithromycin group [95% CI: -4.8%, +8.9%] in the ITT population and 94.0% cethromycin clinical cure rate compared with 93.8% clarithromycin cure rate [95% CI: -4.5%, +5.1%] in the PPc population. Study CL06-001 achieved 82.9% cethromycin clinical cure rate in the ITT population compared with 88.5% clarithromycin cure rate [95% CI: -11.9%, +0.6%], whereas the clinical cure rate in the PPc population was 91.5% in cethromycin group compared with 95.9% in clarithromycin group [95% CI: -9.1%, +0.3%]. Both studies met the primary endpoints for clinical cure rate based on pre-defined, sliding-scale non-inferiority design. Therefore, in comparison with clarithromycin, these two non-inferiority studies demonstrated the efficacy and safety of cethromycin, with encouraging findings of efficacy in subjects with S. pneumoniae bacteremia. No clinically significant adverse events were observed during the studies. Cethromycin may be a potential oral therapy for the outpatient treatment of CAP.

PMID: 22290969 [PubMed - as supplied by publisher]

A prospective observational study comparing three different treatment regimes in patients with Clostridium difficile infection.

Antimicrob Agents Chemother. 2012 Jan 17;

Authors: Wenisch JM, Schmid D, Kuo HW, Allerberger F, Michl V, Tesik P, Tucek G, Laferl H, Wenisch C

Abstract
ObjectiveTo test the effects of the three standard treatment regimens for mild Clostridium difficile infection (CDI) on the risk of complications, sequelae and all-cause death within 30 days after starting treatment.MethodsIn a hospital-based, prospective cohort study the three standard treatment regimens of oral (p.o.) metronidazole 3 × 500 mg/d, intravenous (i.v.) metronidazole 3 × 500 mg/d and oral (p.o.) vancomycin 4 × 250 mg/d, for mild CDI were compared with respect to occurrence of complications, sequelae and all-cause death within 30 days after date of starting treatment. Differences in the incidence of these outcomes were tested by ?2 or Fisher's exact tests. A Poisson regression model was performed to control for possible confounding effects of sex, age and severity of comorbidity categorized according to the Charlson comorbidity index.ResultsThe highest mortality was observed in the metronidazole i.v. group with 38.1% (16/42) compared to 7.4% (9/121) in the metronidazole p.o. group and 9.5% (4/42) in the vancomycin p.o. group (p<0.001). After adjustment for possible effects of sex, age (> 65 years) and severity of comorbidity, the relative risk of 30-day fatal outcome for patients receiving metronidazole i.v. was 4.3 (95%CI 1.92-10; p<0.0001) as compared to patients with metronidazole p.o. and 4.0 (95%CI: 1.31-5.0; p<0.015) compared to patients treated with vancomycin p.o. There were no significant differences in the risk of complications between the three treatment groups.ConclusionThis study generates the hypothesis that treatment with i.v. metronidazole is inferior to the oral alternatives metronidazole and vancomycin.

PMID: 22252830 [PubMed - as supplied by publisher]

Trends in the Susceptibility of Clinically Important Resistant Bacteria to Tigecycline: Results from the Tigecycline In-vitro Surveillance in Taiwan (TIST), 2006-2010.

Antimicrob Agents Chemother. 2011 Dec 27;

Authors: Chen YH, Lu PL, Huang CH, Liao CH, Lu CT, Chuang YC, Tsao SM, Chen YS, Liu YC, Chen WY, Jang TN, Lin HC, Chen CM, Shi ZY, Pan SC, Yang CL, Kung HC, Liu CE, Cheng YJ, Liu JW, Sun W, Wang LS, Ko WC, Yu KW, Chiang PC, Lee MH, Lee CM, Hsu GJ, Hsueh PR

Abstract
The Tigecycline In-vitro Surveillance in Taiwan (TIST), a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) (n=1,834), penicillin-resistant Streptococcus pneumoniae (PRSP) (n=423), vancomycin-resistant enterococci (VRE) (n=219), extended-spectrum ?-lactamase (ESBL)-producing Escherichia coli (n=1,141), ESBL-producing Klebsiella pneumoniae (n=1,330), Acinetobacter baumannii (n=1,645), and Stenotrophomonas maltophilia (n=903), from different specimens from 20 different hospitals in Taiwan. Minimum inhibitory concentrations (MICs) of tigecycline were determined following the criteria of the US Food and Drug Administration (FDA) and European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011).Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC(90), 0.03 ?g/ml) and only one MRSA isolate (MIC(90), 0.5 ?g/ml) and three VRE isolates (MIC(90), 0.125 ?g/ml) were non-susceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producing E. coli (MIC(90), 0.5 ?g/ml) and 96.32% for ESBL-producing K. pneumoniae (MIC(90), 2 ?g/ml), when interpreted by FDA criteria, but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility of A. baumannii (MIC(90), 4 ?g/ml) decreased from 80.9% in 2006 to 55.3% in 2009, but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptible A. baumannii isolates and an unimodal MIC distribution was found among carbapenem-nonsusceptible A. baumannii isolates. In Taiwan, tigecycline continues to have excellent in vitro activity against several major clinically important drug-resistant bacteria, with the exception of A. baumannii.

PMID: 22203598 [PubMed - as supplied by publisher]