Carlos Bantar

Multicenter Study to Assess the in vitro Activity of Tigecycline by Disk Diffusion Test against Clinical Isolates from Argentina

Background: Tigecycline is a new antibiotic currently used in healthcare environments where multidrug resistance is prominent. Because there is a constant potential for resistance to emerge, survey studies are needed. Methods: Isolates collected in 20 clinical laboratories from 4 states of Argentina between November 2005 and October 2006 were tested using the disk diffusion method as described by the CLSI. Results: A total of 3,182 isolates were assessed. Gram-positive cocci represented 43.4% of the total isolates [Staphylococcus aureus (878), coagulase-negative staphylococci (255), Enterococcus spp. (201), Streptococcus spp. (47)], Enterobacteriaceae 39.6% and Acinetobacter spp. 11.1%. Tigecycline proved equally active against methicillin-resistant and methicillin-susceptible staphylococci, as well as against vancomycin-resistant and vancomycin-susceptible enterococci (100% of susceptibility for all Gram-positive bacteria tested). Tigecycline susceptibility for Enterobacteriaceae, other than Proteeaetribe and Serratia spp., ranged from 88 to 100%, including against strains with resistance to third-generation cephalosporins with phenotype of extended spectrum β-lactamases (extended spectrum β-lactamase-positive Escherichia coli 17.7% and extended spectrum β-lactamase-positive Klebsiella pneumoniae 50.5%). Adopting a resistant breakpoint of 16 mm, 92% of the Acinetobacter isolates were susceptible to tigecycline. Conclusion(s): Tigecycline was active against a wide variety of bacterial species, including most of the multidrug-resistant Gram-negative and Gram-positive bacteria. Therefore, it could be a suitable option in the treatment of infections caused by these organisms in hospitalized patients.

Comparative In Vitro Activity of Tigecycline Against Bacteria Recovered from Clinical Specimens in Latin America

Abstract The present study was performed to evaluate the In Vitro activity of tigecycline in comparison to other agents against isolates recovered from patients hospitalized in latin American. Organisms were collected in 47 clinical laboratories from 4 countries of latin America between November 2005 and October 2006 and were tested by using disk diffusion method as described by the CLSI. A total of 7966 isolates were assessed. Tigecycline proved highly active against staphylococci and enterococci (>99% susceptibility). Imipenem was the most active agent against Escherichia coli (100% susceptibility), followed by tigecycline, 98.6% susceptibility. Resistance to cefotaxime in this species was 15.3%. Global tigecycline susceptibility of Klebsiella species was 90.2%, but the susceptibility rate was significantly slower in Venezuela (82%) than in Argentina, Colombia and Chile (93%) (p<0.01). Global cefotaxime resistance to Klebsiella spp. was 32.2% and carbapenem resistance was detected in all countries. By adopting a susceptible breakpoint ≥16mm, 91.3% of the Acinetobacter isolates proved susceptible to tigecycline. Results from the present study suggest that tigecycline may be a suitable option in latin America, a region where multidrug resistance seems to be a dramatic, increasing problem and new antimicrobial choices are urgently needed.

Impact of outpatient neuraminidase inhibitor treatment in patients infected with influenza A(H1N1)pdm09 at high risk of hospitalization: an Individual Participant Data (IPD) meta-analysis

Summary Our findings suggest that in populations at high risk for hospital admission, patients with laboratory-confirmed or clinically diagnosed A(H1N1)pdm09 infection, NAI treatment in the community or outpatient settings is associated with reduced likelihood of subsequent hospital admission.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection.

A Pharmacodynamic Model to Support a 12-Hour Dosing Interval for Amoxicillin/Sulbactam, a Novel Oral Combination, in the Treatment of Community-Acquired Lower Respiratory Tract Infections

Abstract We evaluated, by time-kill studies, the pharmacodynamics of amoxicillin/sul-bactam (AMX/SUL, 875 mg/125 mg), a novel oral combination, against the major respiratory pathogens in 12 volunteers receiving a single dose. The sera corresponding to 50% of a 12-h dosing interval displayed either bactericidal or inhibitory activity against both a penicillin-susceptible and a penicillin-intermediate Streptococcus pneumoniae strain (penicillin MIC of 0.03 and 0.25 μg/ml, respectively), as well as against a β-lactamase-positive Moraxella catarrhalis and a β-lactamase-negative Haemophilus influenzae strain. Both the peak samples and those corresponding to 4 h after dose (i.e. 33% of a 12-h dosing interval) proved active against both a penicillin-resistant S. pneumoniae (MIC, 2 μg/ml) and a β-lactamase-positive H. influenzae strain. The AMX-SUL formulation evaluated in this study showed pharmacodynamic features that support clinical trials to assess its efficacy in the treatment of lower respiratory tract infections with a 12-h dosing interval regimen.

Rationale for Treating Community-Acquired Lower Respiratory Tract Infections with Amoxicillin/Sulbactam Combination Through Pharmacodynamic Analysis in the Setting of Aminopenicillin-Resistant Organisms

Abstract In order to establish a rationale for treating community-acquired lower respiratory tract infections, we assess here the pharmacodynamics of amoxi-cillin/sulbactam, 500mg/500mg, a formulation marketed in Argentina since 1988 and currently available in 17 countries, against the major pathogens, in comparison with that of a novel formulation (875mg/125mg, see J Chemother 2000; 12: 223-227). In time-kill studies, both bactericidal and inhibitory activity were seen in the 1.5- and 6-h sera, obtained from 12 volunteers after a single oral dose, against both a penicillin-susceptible and an -intermediate Streptococcus pneumoniae strain, as well as against Moraxella catarrhalis and a β-lactamase-negative Haemophilus influenzae strain. Only the 1.5-h sera proved bactericidal against a penicillin-resistant S. pneumoniae strain (MIC, 2 μg/ml) and a β-lactamse-positive H. influenzae isolate. This study suggests that amoxicillin/sulbactam (500mg/500mg) is still a suitable option for treating community-acquired lower respiratory tract infections, allowing a b.i.d. dosing schedule. Caution should be taken with pneumonia caused by β-lacta-mase-positive H. influenzae or penicillin-resistant (MIC >2 μg/ml) S. pneumoniae isolates. Either shorter dosing intervals (t.i.d.) or a higher amoxicillin content in the formulation (i.e. 875 mg) may be required in these situations.

An ex-vivo pharmacodynamic study comparing bactericidal activity of amoxicillin/sulbactam, azithromycin, doxycycline and levofloxacin against Streptococcus pneumoniae.

Abstract We designed a 4-way crossover, Ex-Vivo pharmacodynamic study to compare the bactericidal rate of amoxicillin/sulbactam (AMX-SUL), azithromycin (AZM), doxycycline (DOX) and levofloxacin (LVX) against Streptococcus pneumoniae ATCC 49619. Six volunteers were randomized to receive alternatively a single tablet of the above drugs. Venous blood samples were obtained immediately before and at 2, 4 and 6 h after dose to perform time-kill studies and to determine antibiotic levels in serum. AMX-SUL was the only drug showing bactericidal activity with the sera obtained at every time after dose, as defined by a ≥ 3-log10 cfu/ml decrease in the viable cell counts compared to the original inoculum after a 24-h incubation. AZM was only inhibitory at 2h after dose (i.e. a 1.3-log10 cfu/ml decrease in the viable cell counts) and proved bactericidal at 4 and 6 h post-dose. LVX proved bactericidal with the 2-h serum, was only inhibitory with the 4-h serum (e.g. a 1.5- log10 cfu/ml decrease) and was unable to avoid bacterial growth at 6 h post-dose. Bacterial growth was observed with DOX at every time after dose. This study may shed light on the understanding of breakthrough pneumococcal bacteremia during the course of oral therapy with AZM in patients with community-acquired pneumonia (CAP), as well as the increasing treatment failures observed with LVX, and the selection of bacterial resistance during therapy reported with both drugs. It also provides the basis for a “warning signal” on the use of oral DOX and confirms the efficacy of AMX-SUL.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an IPD meta-analysis.

The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia

The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection.

Intravenous Amoxicillin-Sulbactam against Escherichia coli: Optimizing the Dose, Component Ratio and Infusion Time Using a Human Pharmacodynamic Model

Abstract Amoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/β-lactamase inhibitor combination currently available in 29 countries which may be a suitable option for treating intra-abdominal infections. The aim of this study was to identify the optimal dose and ratio between components of this formulation through an ex-vivo human pharmacodynamic model against Escherichia Coli. Four volunteers were randomized to receive alternatively a single dose of AMX-SUL infused either over 30 min or 3h in the following ratios (g/g): 1/0.5; 1/1, 2/0.5 and 0/2. Time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6- and 8-h post-dosing sera against E. coli ATCC 25922 (AMX MIC, 2 μg/mL; AMX-SUL MIC, 2 μg/mL) and E. coli ATCC 35218 (AMX MIC, 1024 μg/mL; AMX-SUL MIC, 4-8 μg/mL). AMX-SUL 1g/0.5g infused over 30 min was only active at 0.5 h after dose, being inferior to both AMX-SUL 1g/1g and AMX-SUL 2g/0.5g against E. coli ATCC 25922, for which the 2h post-dose serum proved active. When tested against E. coli AtCC 35218, AMX-SUL 1g/0.5g and AMX-SUL 2g/0.5g were active only at 0.5h post-dose, whereas AMX-SUL 1g/1g showed bactericidal activity 0.5h post-dose and was able to inhibit bacterial growth 2h post-dose. When infused over 3h, the antimicrobial activity of AMX-SUL was better than the 30-min infusion. Moreover, AMX-SUL 1g/1g was able to inhibit, and kill to some extent, the E. coli ATCC 25922 strain at 4h post-dose (i.e. 67% and 50% of a 6- and 8-h dosing interval, respectively). The present study suggests that 1g/1g is the best formulation for AMX-SUL against E. coli. The infusion over 3h optimizes its pharmacodynamic profile, as well as that of the 1g/0.5g combination. These findings encourage the performance of clinical trials to assess the efficacy of this combination, given as an extended infusion, in the treatment of community-acquired intra-abdominal infections.