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Papers by Caio Mendes
Pediatric Infectious Disease Journal, 1988
Two hundred fifty-eight isolates of Streptococcus pneumoniae obtained from 232 infants and childr... more Two hundred fifty-eight isolates of Streptococcus pneumoniae obtained from 232 infants and children at Children's Medical Center, Dallas, from November 1, 1981, to March 31, 1983, were screened for susceptibility to penicillin. On 1-microgram oxacillin disks 21 strains (8%) had zones of inhibition of 17 mm or less, and the tube-dilution minimal inhibitory concentrations of penicillin were from 0.125 to 0.5 micrograms/ml. These strains were designated as relatively resistant S. pneumoniae (RRSP). Prior therapy with a beta-lactam agent had occurred in 56% of patients with RRSP disease compared with 14% of randomly selected children with infections due to susceptible strains of S. pneumoniae (P = 0.009). Fifteen children (6%) had diseases due to RRSP ranging from sepsis or meningitis to otitis media or conjunctivitis. Four children, including the two patients with meningitis, had unsatisfactory responses to therapy with a beta-lactam antibiotic. Vancomycin or chloramphenicol is preferred for therapy of disease due to RRSP.
International Journal of Antimicrobial Agents, 2007
Objectives: As a result of increasing resistance among Pseudomonas aeruginosa (PSA), alternative ... more Objectives: As a result of increasing resistance among Pseudomonas aeruginosa (PSA), alternative dosing strategies to optimise piperacillin/tazobactam (TZP) pharmacodynamics, such as prolonged (PI) and continuous infusion (CI), have been advocated; however, comparative data to aid in deciding which to use are sparse. Monte Carlo simulation was utilised to compare the bactericidal cumulative fraction of response (CFR) between PI and CI regimens against a local population of PSA. Methods: TZP pharmacokinetics were extrapolated from a published population pharmacokinetic study in surgical and neutropenic patients. A 2-compartment model was used to calculate steady-state concentration time profiles for the piperacillin component of the following TZP dosages: 4.5 g q6h (30 minute infusion), 3.375 g q8h (4 h PI), 4.5 g q8h (4 h PI), 4.5 g q6h (3 h PI), 10.125 g CI, 13.5 g CI, 18 g CI, 20.25 g CI, and 22.5 g CI. A 5,000 Monte Carlo simulation with covariance matrix was conducted. Pharmacodynamic targets were 50% free time above the MIC (T >MIC ) for the 30 minute infusion and PI regimens, and 100% free T >MIC for CI regimens. MICs for 416 consecutive nonduplicate PSA collected from our institution over a 6 month period during 2006 were tested via E-test. Results: 92.3% of PSA were TZP susceptible; the MIC50 and MIC 90 were 8 and 32 mg/mL, respectively. CFR was 79.6 (4.5 g q6h, 30 minute infusion), 83.1 (3.375 g q8h, 4 h PI), 86.9 (4.5 g q8h, 4 h PI), 89.6 (4.5 g q6h, 3 h PI), 82.0 (10.125 g CI), 86.3 (13.5 g CI), 89.2 (18 g CI), 90.0 (20.25 g CI), and 90.6 (22.5 g CI). Conclusion: Both PI and CI dosing strategies improve the pharmacodynamics of TZP over that of standard infusion regimens; moreover, PI and CI regimens that contain the same daily piperacillin dose will have similar likelihood of bactericidal exposure. Thus, the choice of administration strategy depends on the convenience of once daily dosing versus line access availability. Finally, dosing regimens that contained greater than 18 g TZP daily did not appear to provide any meaningful additional exposure for this PSA population.
Brazilian Journal of Infectious Diseases, 2001
The in vitro antimicrobial susceptibility of the respiratory pathogens Streptococcus pneumoniae, ... more The in vitro antimicrobial susceptibility of the respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis to commonly tested and prescribed agents was investigated during 1999-2000 and compared with results obtained during a previous 1997-1998 study. Of 448 isolates of S. pneumoniae collected and tested in 1999-2000, 77.2% were susceptible, 19.9% were intermediate, and 2.9% were resistant to penicillin, demonstrating that there were no major changes in susceptibility to penicillin from 1997-1998 (77.1% susceptible, 18.7% intermediate, 4.2% resistant). All S. pneumoniae isolates from 1999-2000 were susceptible to levofloxacin and vancomycin, and >90% were susceptible to the b-lactams (amoxicillin-clavulanate, ceftriaxone, and cefuroxime) and macrolides (azithromycin and clarithromycin), showing that susceptibility to these agents also remained unchanged since 1997-1998. The most notable increase in resistance between the two studies was demonstrated by trimethoprim-sulfamethoxazole, which increased from 23.4% to 38.6%. Penicillin resistance correlated with resistance to b-lactams, macrolides, and trimethoprim-sulfamethoxazole in both studies. In H. influenzae, the prevalence of b-lactamase-producing isolates remained unchanged (10.6% in 1999-2000; 11.0% in 1997-1998). All H. influenzae isolates were susceptible to levofloxacin, ceftriaxone, cefuroxime, and azithromycin, and showed no change between the two studies. Trimethoprim-sulfamethoxazole resistance was present in 40.1% of isolates in 1999-2000, and in 45.2% in 1997-1998. In M. catarrhalis, the prevalence of b-lactamase-producing isolates was unchanged (97.9% in 1999-2000; 98.0% in 1997-1998). The most active agents against M. catarrhalis were azithromycin (MIC90, <0.03 mg/ml) and levofloxacin (MIC90, 0.03 mg/ml). Overall, these results suggest that, in Brazil, between 1999-2000 and 1997-1998, there have been no significant changes in the susceptibility of respiratory pathogens to any of the commonly tested and prescribed agents with the exception of trimethoprim-sulfamethoxazole for S. pneumoniae.
Clinical Microbiology and Infection, 2002
Bacterial resistance to antibiotics in community-acquired respiratory tract infections is a serio... more Bacterial resistance to antibiotics in community-acquired respiratory tract infections is a serious problem and is increasing in prevalence world-wide at an alarming rate. Streptococcus pneumoniae, one of the main organisms implicated in respiratory tract infections, has developed multiple resistance mechanisms to combat the effects of most commonly used classes of antibiotics, particularly the β-lactams (penicillin, aminopenicillins and cephalosporins) and macrolides. Furthermore, multidrug-resistant strains of S. pneumoniae have spread to all regions of the world, often via resistant genetic clones. A similar spread of resistance has been reported for other major respiratory tract pathogens, including Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. To develop and support resistance control strategies it is imperative to obtain accurate data on the prevalence, geographic distribution and antibiotic susceptibility of respiratory tract pathogens and how this relates to antibiotic prescribing patterns. In recent years, significant progress has been made in developing longitudinal national and international surveillance programs to monitor antibiotic resistance, such that the prevalence of resistance and underlying trends over time are now well documented for most parts of Europe, and many parts of Asia and the Americas. However, resistance surveillance data from parts of the developing world (regions of Central America, Africa, Asia and Central/Eastern Europe) remain poor. The quantity and quality of surveillance data is very heterogeneous; thus there is a clear need to standardize or validate the data collection, analysis and interpretative criteria used across studies. If disseminated effectively these data can be used to guide empiric antibiotic therapy, and to support—and monitor the impact of—interventions on antibiotic resistance.
Clinical Microbiology and Infection, 2004
Tzouvelekis LS et al. Spread of integron-associated VIM-type metallo-b-lactamase genes among imip... more Tzouvelekis LS et al. Spread of integron-associated VIM-type metallo-b-lactamase genes among imipenem-nonsusceptible Pseudomonas aeruginosa strains in Greek hospitals. J Clin Microbiol 2003; 41: 822-825. 19. Lauretti L, Riccio ML, Mazzariol A et al. Cloning and characterization of bla VIM , a new integron-borne metallob-lactamase gene from a Pseudomonas aeruginosa clinical isolate.
Clinical Microbiology and Infection, 2000
Diagnostic Microbiology and Infectious Disease, 2001
The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudina... more The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal global antimicrobial surveillance study that compares the activity of meropenem and comparator antimicrobial agents against pathogens isolated from intensive care, neutropenic or cystic fibrosis patients, and general wards. Data from the different European MYSTIC Program units (1997 showed that the most prevalent isolates tested overall were methicillin-susceptible Staphylococcus aureus (MSSA; in accordance with study design methicillin-resistant S. aureus was not tested), Pseudomonas aeruginosa and Escherichia coli. In all the unit types, E. coli (approximately 20% having an extended spectrum -lactamase phenotype) and MSSA were highly susceptible to meropenem (97-99% susceptibility). Isolates of MSSA showed lower levels of susceptibility to ciprofloxacin (61-77% susceptibility) in both cystic fibrosis and neutropenia patients, and particularly high levels of resistance to ceftazidime (38% susceptibility) in cystic fibrosis units. Ciprofloxacin (54% susceptibility) and gentamicin (46% susceptibility) demonstrated low levels of activity against P. aeruginosa (frequently encountered in cystic fibrosis units). Meropenem and piperacillin/tazobactam were the most active agents against P. aeruginosa in all the unit types. Carbapenems and piperacillin/tazobactam have sustained Ͼ 90% susceptibility rates overall against the most frequently isolated pathogens. The analysis of specific units that house patients with a high-risk of contracting antimicrobial-resistant pathogens remains very important for the optimal selection of empiric regimens.
Infection Control and Hospital Epidemiology, 1995
Infections due to coagulase-negative Staphylococcus (CNS) are an ever-increasing nosocomial probl... more Infections due to coagulase-negative Staphylococcus (CNS) are an ever-increasing nosocomial problem, particularly in the pediatric population. The authors describe a cluster of three primary bloodstream infections due to CNS in a newborn intensive care unit that occurred between November 23 and December 2, 1992. Two children died as a direct consequence of the bacteremia; at autopsy, one had a large bacteria-containing thrombus extending from the insertion site of a central catheter to the superior vena cava. The children were placed in isolation, and the nursing and medical staff were given topical nasal mupirocin. Plasmid analysis performed later disclosed three different blood isolates that also were different from any of the staff's nasal isolates. The authors concluded that molecular methods such as plasmid analysis are important tools in identifying true outbreaks and can prevent needless interventions, such as those during this cluster.
Infection Control and Hospital Epidemiology, 2001
Contamination in an intensive care unit caused by multidrug-resistant Acinetobacter baumannii com... more Contamination in an intensive care unit caused by multidrug-resistant Acinetobacter baumannii complex (MRAB)-colonized patients was evaluated using environmental and patient cultures. MRAB occurred in 21% of patients' cultures, 2.1% of 513 areas surrounding MRAB-patients, and one of 372 common areas. No transmission to other patients occurred. Barrier precautions and ethanol disinfection may prevent dissemination.
Brazilian Journal of Infectious Diseases, 2005
OBJECTIVE: Establish the susceptibility pattern of Gram-negative bacteria causing infections in I... more OBJECTIVE: Establish the susceptibility pattern of Gram-negative bacteria causing infections in ICU patients, MYSTIC Program Brazil 2002. MATERIAL AND METHODS: Gram-negative bacteria (n = 503) causing nosocomial infections were collected at seven Brazilian centers. The central laboratory confirmed the identification and performed the susceptibility tests by E-test methodology (AB Biodisk, Solna, Sweden) for meropenem, imipenem, ciprofloxacin, ceftazidime, cefepime, cefotaxime, piperacillin/tazobactam, gentamicin, and tobramycin. Interpretation criteria used were according to National Committee for Clinical Laboratory Standards (NCCLS). RESULTS: Pseudomonas aeruginosa (33%) was the most frequently isolated, followed by A. baumannii (17.1%), K. pneumoniae (12.1%), E. coli (10.5%), and E. cloacae (7.9%). Pseudomonas aeruginosa isolates had susceptibility rates of 67.5% to piperacillin/tazobactam, 59.8% to meropenem, 57.3% to imipenem. A. baumannii presented susceptibility rates to meropenem of 89.5%, 88.4% to imipenem, and 74.4% to tobramycin. E. coli and K. pneumoniae were fully susceptible to both carbapenems. CONCLUSIONS: Carbapenem resistance among Enterobacteriaceae is still rare in this region. A. baumannii and P. aeruginosa presented elevated resistance rates to all antimicrobials. Since these two bacterial species play an important role in nosocomial infections, the use of empirical combination therapy to treat these pathogens may be justified.
Infection Control and Hospital Epidemiology, 1996
A case-control (46 cases, 23 controls) study was done to determine risk factors for an outbreak o... more A case-control (46 cases, 23 controls) study was done to determine risk factors for an outbreak of a multiresistant Acinetobacter baumanii (only susceptible to colistin) in a university hospital. The use of antecedent antibacterials and intubation were independent risk factors. No common source was found. With control measures, the outbreak resolved gradually.
Brazilian Journal of Infectious Diseases, 2003
Telithromycin) is a global surveillance study established in 1999 to monitor antibacterial resist... more Telithromycin) is a global surveillance study established in 1999 to monitor antibacterial resistance of respiratory tract organisms. Thirteen centers from Argentina, Brazil and Mexico participated during 1999-2000; they collected 1,806 isolates (Streptococcus pneumoniae 518, Haemophilus influenzae 520, Moraxella catarrhalis 140, Staphylococcus aureus 351, S. pyogenes 277). Overall, 218 (42.1%) of the S. pneumoniae isolates had reduced susceptibility to penicillin, 79 (15.3%) were penicillin-resistant and 79 (15.3%) were erythromycin-resistant. Mexico had the highest prevalence of penicillin (76.5%) and erythromycin (31.2%) resistance. Of 77 erythromycinresistant S. pneumoniae tested for resistance genotype, 43 possessed mef(A), 33 possessed erm(B) and 1 possessed both erm(B) and mef(A) mechanism. All S. pneumoniae isolates were fully susceptible to telithromycin, linezolid, teicoplanin and vancomycin. Among H. influenzae isolates, 88 (16.9%) produced β
Diagnostic Microbiology and Infectious Disease, 2004
The OPTAMA (Optimizing Pharmacodynamic Target Attainment using the MYSTIC [Meropenem Yearly Susce... more The OPTAMA (Optimizing Pharmacodynamic Target Attainment using the MYSTIC [Meropenem Yearly Susceptibility Test Information Collection] Antibiogram) Program provides insight into the appropriate antibiotic options for empiric therapy for common nosocomial pathogens. In this report, South America is represented by Brazil, Colombia, Peru, and Venezuela. A 5000-subject Monte Carlo Simulation estimated pharmacodynamic target attainment for meropenem, imipenem, ceftazidime, cefepime, piperacillin/tazobactam, and ciprofloxacin against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Pharmacokinetic parameter variability was derived from existing healthy volunteer data, and minimum inhibitory concentration (MIC) data came from the 2002 MYSTIC program. Piperacillin/tazobactam and ciprofloxacin displayed the lowest target attainment against all bacterial species (14% to 24% for A. baumannii, 26% to 37% for P. aeruginosa, and 48% to 66% for the Enterobacteriaceae). Overall, the carbapenems had the highest probabilities of attainment against the Enterobacteriaceae (98% to 100%) and A. baumannii (73% to 74%), whereas cefepime obtained the greatest target attainment against P. aeruginosa (65%). Because no single regimen had high target attainment against A. baumannii and P. aeruginosa, the use of combination therapy to treat these pathogens in South America may be justified. Because of the lack of agreement with percent susceptibility for certain antimicrobial regimens, the use of pharmacodynamic target attainment may be a more accurate predictor of microbiologic success.
Brazilian Journal of Infectious Diseases, 2005
Establish the susceptibility pattern of Gram-negative bacteria causing infections in ICU patients... more Establish the susceptibility pattern of Gram-negative bacteria causing infections in ICU patients, MYSTIC Program Brazil 2003. Gram-negative bacteria (n = 1,550) causing nosocomial infections were collected at 20 Brazilian centers. The central laboratory confirmed the identification and performed the susceptibility tests by Etest methodology (AB Biodisk, Solna, Sweden) for meropenem, imipenem, ciprofloxacin, ceftazidime, cefepime, cefotaxime, piperacillin/tazobactam, gentamicin, and tobramycin. Interpretation criteria used were according to National Committee for Clinical Laboratory Standards (NCCLS). Pseudomonas aeruginosa (30.3%) was the most frequent isolate, followed by E. coli (18.6%), Klebsiella pneumoniae (16.9%), Acitenobacter baumannii (8.8%), and Enterobacter cloacae (7.1%). Pseudomonas aeruginosa (n=470) isolates presented susceptibility rates of 64% to meropenem, 63.8% to piperacillin/tazobactam, 63.4% to amikacin, 58.7% to imipenem. Acitenobacter baumannii presented susceptibility rates to meropenem of 97.1%, and 73% to tobramycin. E. coli and K. pneumoniae were highly susceptible to both carbapenems.Carbapenem resistance among the Enterobacteriaceae is still rare in the region. Acitenobacter baumannii and P. aeruginosa presented elevated resistance rates to all antimicrobials. Since they play an important role in nosocomial infections in this environment, the use of empirical combination therapy to treat these pathogens may be justified.
Infection Control and Hospital Epidemiology, 1999
A case-control study was done to evaluate factors associated with nosocomial infections by multir... more A case-control study was done to evaluate factors associated with nosocomial infections by multiresistant Pseudomonas aeruginosa (MRPA). Results showed that MRPA was associated with the use of immunosuppressive and antimicrobial drugs. Five typing methods indicated that the MRPA infections were due to multiple strains rather than a single strain.
Brazilian Journal of Infectious Diseases, 2001
Surveillance programs are essential to detect the increase of antimicrobial resistance, and sever... more Surveillance programs are essential to detect the increase of antimicrobial resistance, and several different programs are being conducted in many countries. The RESISTNET is a surveillance program for bacterial resistance against several antimicrobial agents initiated in 1998 among Latin American countries. In Brazil, several centers were invited to join this surveillance and a total of 11 centers (6 from São Paulo and 5 from other states) participated in the study. All results were analyzed using the WHONET program. A total of 894 Escherichia coli, 386 Klebsiella pneumoniae, 70 Shigella spp and 57 Salmonella spp strains were analyzed in this study from April, 1998, to April, 1999. Susceptibility testing was performed by the disk diffusion method using NCCLS 1998 guidelines for several different drugs. For all strains, imipenem was the most effective drug (100% of the strains were susceptible). Klebsiella pneumoniae presented a high resistance rate to ampicillin (96.4%). The rate of probable ESBL producers among K. pneumoniae strains was 36.3%, most of them being isolated from catheters (58.8%). Among all Escherichia coli strains analyzed, the highest resistance rate was found for trimethoprim/sulfamethoxazole (46.9%) and the majority of the resistant strains were isolated from urine samples (47.8%). Among Salmonella spp, the resistance rates were low for all antibiotics tested. For Shigella spp strains there was a high resistance to trimethoprim/sulfamethoxazole (80.0%). No resistance to ceftriaxone was observed in these strains. Surveillance of antimicrobial resistance is critical for the successful management of infectious diseases. The results of this survey show significant resistance rates among these bacteria which are responsible for several types of human infections.
Diagnostic Microbiology and Infectious Disease, 2005
Meropenem and imipenem are often the drugs of choice for the treatment of infections due to multi... more Meropenem and imipenem are often the drugs of choice for the treatment of infections due to multidrug-resistant Acinetobacter baumannii. The present study aimed at evaluating the interaction between meropenem and sulbactam through microdilution and checkerboard methods against 48 clinical isolates of A. baumannii collected from Brazilian hospitals. All the isolates presented elevated minimum inhibitory concentration (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=2 microg/mL) to either meropenem or sulbactam. The checkerboard method with the combination of meropenem and sulbactam demonstrated 29.2% (14/48) synergism, 47.9% (23/48) partial synergism, 10.5% (5/48) additive, 6.2% (3/48) indifference, and 6.2% (3/48) antagonism (SigmaFIC(min)=0.09 and SigmaFIC(max)=8). Thus, combinations of meropenem and sulbactam may show synergism or partial synergism for most A. baumannii isolates. Further studies may help identify treatment options for patients with infections caused by these organisms, particularly with this combination, where both drugs have time-dependent activities and might be suitable for therapy optimization studies.
International Journal of Antimicrobial Agents, 2006
The pharmacodynamic potency of imipenem, meropenem and ertapenem against extended-spectrum -lact... more The pharmacodynamic potency of imipenem, meropenem and ertapenem against extended-spectrum -lactamase (ESBL)-producing isolates was investigated. Minimal inhibitory concentration (MIC) determination, confirmation of ESBLs by Etest and the disk approximation test were performed for 133 ESBL-producing isolates of Escherichia coli and Klebsiella spp. Pharmacodynamic exposure, measured as percent of the dosing interval during which free drug was above the MIC (% fT > MIC), was modelled via a 5000-subject Monte Carlo simulation. Bactericidal cumulative fraction of response (CFR), defined as 40% fT > MIC, was calculated against each bacterial population. All agents achieved high bactericidal CFR against all ESBL isolates as a group, but ertapenem (96.26%) was slightly less effective than imipenem (99.96%) and meropenem (99.90%) (P < 0.05). Similar results were observed against Klebsiella spp. only (P < 0.05). Against E. coli, CFRs were close to 100%. Ertapenem is probably an effective agent against ESBL-producing bacteria, although its ability to achieve bactericidal pharmacodynamic exposures will depend on the bacterial susceptibility.
Diagnostic Microbiology and Infectious Disease, 2005
This overview provides a summary of the Meropenem Yearly Susceptibility Test Information Collecti... more This overview provides a summary of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program over an 8-year period from 1997 to 2004. The evolution of the MYSTIC Program is described, as well as its design compared with other surveillance programs. In addition, the global MYSTIC Program data, published to date, are summarized, and the empiric use of carbapenems, their current indications, and meropenem usage versus resistance was discussed. From 1997 to 2004, 120 medical centers that were actively prescribing meropenem in 32 countries worldwide participated in the program. The MYSTIC Program results demonstrate the sustained potency and continued effectiveness of meropenem globally against clinically relevant Gram-negative and Gram-positive pathogens including extended spectrum beta-lactamase- and AmpC beta-lactamase-producing organisms, which may also display resistance to the fluoroquinolones and/or aminoglycosides. Furthermore, in centers actively prescribing meropenem, resistance to meropenem is not increasing despite greater resistance among the comparator antimicrobial agents. Thus, antipseudomonal carbapenems such as meropenem and imipenem remain an effective treatment option.
Pediatric Infectious Disease Journal, 1988
Two hundred fifty-eight isolates of Streptococcus pneumoniae obtained from 232 infants and childr... more Two hundred fifty-eight isolates of Streptococcus pneumoniae obtained from 232 infants and children at Children's Medical Center, Dallas, from November 1, 1981, to March 31, 1983, were screened for susceptibility to penicillin. On 1-microgram oxacillin disks 21 strains (8%) had zones of inhibition of 17 mm or less, and the tube-dilution minimal inhibitory concentrations of penicillin were from 0.125 to 0.5 micrograms/ml. These strains were designated as relatively resistant S. pneumoniae (RRSP). Prior therapy with a beta-lactam agent had occurred in 56% of patients with RRSP disease compared with 14% of randomly selected children with infections due to susceptible strains of S. pneumoniae (P = 0.009). Fifteen children (6%) had diseases due to RRSP ranging from sepsis or meningitis to otitis media or conjunctivitis. Four children, including the two patients with meningitis, had unsatisfactory responses to therapy with a beta-lactam antibiotic. Vancomycin or chloramphenicol is preferred for therapy of disease due to RRSP.
International Journal of Antimicrobial Agents, 2007
Objectives: As a result of increasing resistance among Pseudomonas aeruginosa (PSA), alternative ... more Objectives: As a result of increasing resistance among Pseudomonas aeruginosa (PSA), alternative dosing strategies to optimise piperacillin/tazobactam (TZP) pharmacodynamics, such as prolonged (PI) and continuous infusion (CI), have been advocated; however, comparative data to aid in deciding which to use are sparse. Monte Carlo simulation was utilised to compare the bactericidal cumulative fraction of response (CFR) between PI and CI regimens against a local population of PSA. Methods: TZP pharmacokinetics were extrapolated from a published population pharmacokinetic study in surgical and neutropenic patients. A 2-compartment model was used to calculate steady-state concentration time profiles for the piperacillin component of the following TZP dosages: 4.5 g q6h (30 minute infusion), 3.375 g q8h (4 h PI), 4.5 g q8h (4 h PI), 4.5 g q6h (3 h PI), 10.125 g CI, 13.5 g CI, 18 g CI, 20.25 g CI, and 22.5 g CI. A 5,000 Monte Carlo simulation with covariance matrix was conducted. Pharmacodynamic targets were 50% free time above the MIC (T >MIC ) for the 30 minute infusion and PI regimens, and 100% free T >MIC for CI regimens. MICs for 416 consecutive nonduplicate PSA collected from our institution over a 6 month period during 2006 were tested via E-test. Results: 92.3% of PSA were TZP susceptible; the MIC50 and MIC 90 were 8 and 32 mg/mL, respectively. CFR was 79.6 (4.5 g q6h, 30 minute infusion), 83.1 (3.375 g q8h, 4 h PI), 86.9 (4.5 g q8h, 4 h PI), 89.6 (4.5 g q6h, 3 h PI), 82.0 (10.125 g CI), 86.3 (13.5 g CI), 89.2 (18 g CI), 90.0 (20.25 g CI), and 90.6 (22.5 g CI). Conclusion: Both PI and CI dosing strategies improve the pharmacodynamics of TZP over that of standard infusion regimens; moreover, PI and CI regimens that contain the same daily piperacillin dose will have similar likelihood of bactericidal exposure. Thus, the choice of administration strategy depends on the convenience of once daily dosing versus line access availability. Finally, dosing regimens that contained greater than 18 g TZP daily did not appear to provide any meaningful additional exposure for this PSA population.
Brazilian Journal of Infectious Diseases, 2001
The in vitro antimicrobial susceptibility of the respiratory pathogens Streptococcus pneumoniae, ... more The in vitro antimicrobial susceptibility of the respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis to commonly tested and prescribed agents was investigated during 1999-2000 and compared with results obtained during a previous 1997-1998 study. Of 448 isolates of S. pneumoniae collected and tested in 1999-2000, 77.2% were susceptible, 19.9% were intermediate, and 2.9% were resistant to penicillin, demonstrating that there were no major changes in susceptibility to penicillin from 1997-1998 (77.1% susceptible, 18.7% intermediate, 4.2% resistant). All S. pneumoniae isolates from 1999-2000 were susceptible to levofloxacin and vancomycin, and >90% were susceptible to the b-lactams (amoxicillin-clavulanate, ceftriaxone, and cefuroxime) and macrolides (azithromycin and clarithromycin), showing that susceptibility to these agents also remained unchanged since 1997-1998. The most notable increase in resistance between the two studies was demonstrated by trimethoprim-sulfamethoxazole, which increased from 23.4% to 38.6%. Penicillin resistance correlated with resistance to b-lactams, macrolides, and trimethoprim-sulfamethoxazole in both studies. In H. influenzae, the prevalence of b-lactamase-producing isolates remained unchanged (10.6% in 1999-2000; 11.0% in 1997-1998). All H. influenzae isolates were susceptible to levofloxacin, ceftriaxone, cefuroxime, and azithromycin, and showed no change between the two studies. Trimethoprim-sulfamethoxazole resistance was present in 40.1% of isolates in 1999-2000, and in 45.2% in 1997-1998. In M. catarrhalis, the prevalence of b-lactamase-producing isolates was unchanged (97.9% in 1999-2000; 98.0% in 1997-1998). The most active agents against M. catarrhalis were azithromycin (MIC90, <0.03 mg/ml) and levofloxacin (MIC90, 0.03 mg/ml). Overall, these results suggest that, in Brazil, between 1999-2000 and 1997-1998, there have been no significant changes in the susceptibility of respiratory pathogens to any of the commonly tested and prescribed agents with the exception of trimethoprim-sulfamethoxazole for S. pneumoniae.
Clinical Microbiology and Infection, 2002
Bacterial resistance to antibiotics in community-acquired respiratory tract infections is a serio... more Bacterial resistance to antibiotics in community-acquired respiratory tract infections is a serious problem and is increasing in prevalence world-wide at an alarming rate. Streptococcus pneumoniae, one of the main organisms implicated in respiratory tract infections, has developed multiple resistance mechanisms to combat the effects of most commonly used classes of antibiotics, particularly the β-lactams (penicillin, aminopenicillins and cephalosporins) and macrolides. Furthermore, multidrug-resistant strains of S. pneumoniae have spread to all regions of the world, often via resistant genetic clones. A similar spread of resistance has been reported for other major respiratory tract pathogens, including Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. To develop and support resistance control strategies it is imperative to obtain accurate data on the prevalence, geographic distribution and antibiotic susceptibility of respiratory tract pathogens and how this relates to antibiotic prescribing patterns. In recent years, significant progress has been made in developing longitudinal national and international surveillance programs to monitor antibiotic resistance, such that the prevalence of resistance and underlying trends over time are now well documented for most parts of Europe, and many parts of Asia and the Americas. However, resistance surveillance data from parts of the developing world (regions of Central America, Africa, Asia and Central/Eastern Europe) remain poor. The quantity and quality of surveillance data is very heterogeneous; thus there is a clear need to standardize or validate the data collection, analysis and interpretative criteria used across studies. If disseminated effectively these data can be used to guide empiric antibiotic therapy, and to support—and monitor the impact of—interventions on antibiotic resistance.
Clinical Microbiology and Infection, 2004
Tzouvelekis LS et al. Spread of integron-associated VIM-type metallo-b-lactamase genes among imip... more Tzouvelekis LS et al. Spread of integron-associated VIM-type metallo-b-lactamase genes among imipenem-nonsusceptible Pseudomonas aeruginosa strains in Greek hospitals. J Clin Microbiol 2003; 41: 822-825. 19. Lauretti L, Riccio ML, Mazzariol A et al. Cloning and characterization of bla VIM , a new integron-borne metallob-lactamase gene from a Pseudomonas aeruginosa clinical isolate.
Clinical Microbiology and Infection, 2000
Diagnostic Microbiology and Infectious Disease, 2001
The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudina... more The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal global antimicrobial surveillance study that compares the activity of meropenem and comparator antimicrobial agents against pathogens isolated from intensive care, neutropenic or cystic fibrosis patients, and general wards. Data from the different European MYSTIC Program units (1997 showed that the most prevalent isolates tested overall were methicillin-susceptible Staphylococcus aureus (MSSA; in accordance with study design methicillin-resistant S. aureus was not tested), Pseudomonas aeruginosa and Escherichia coli. In all the unit types, E. coli (approximately 20% having an extended spectrum -lactamase phenotype) and MSSA were highly susceptible to meropenem (97-99% susceptibility). Isolates of MSSA showed lower levels of susceptibility to ciprofloxacin (61-77% susceptibility) in both cystic fibrosis and neutropenia patients, and particularly high levels of resistance to ceftazidime (38% susceptibility) in cystic fibrosis units. Ciprofloxacin (54% susceptibility) and gentamicin (46% susceptibility) demonstrated low levels of activity against P. aeruginosa (frequently encountered in cystic fibrosis units). Meropenem and piperacillin/tazobactam were the most active agents against P. aeruginosa in all the unit types. Carbapenems and piperacillin/tazobactam have sustained Ͼ 90% susceptibility rates overall against the most frequently isolated pathogens. The analysis of specific units that house patients with a high-risk of contracting antimicrobial-resistant pathogens remains very important for the optimal selection of empiric regimens.
Infection Control and Hospital Epidemiology, 1995
Infections due to coagulase-negative Staphylococcus (CNS) are an ever-increasing nosocomial probl... more Infections due to coagulase-negative Staphylococcus (CNS) are an ever-increasing nosocomial problem, particularly in the pediatric population. The authors describe a cluster of three primary bloodstream infections due to CNS in a newborn intensive care unit that occurred between November 23 and December 2, 1992. Two children died as a direct consequence of the bacteremia; at autopsy, one had a large bacteria-containing thrombus extending from the insertion site of a central catheter to the superior vena cava. The children were placed in isolation, and the nursing and medical staff were given topical nasal mupirocin. Plasmid analysis performed later disclosed three different blood isolates that also were different from any of the staff's nasal isolates. The authors concluded that molecular methods such as plasmid analysis are important tools in identifying true outbreaks and can prevent needless interventions, such as those during this cluster.
Infection Control and Hospital Epidemiology, 2001
Contamination in an intensive care unit caused by multidrug-resistant Acinetobacter baumannii com... more Contamination in an intensive care unit caused by multidrug-resistant Acinetobacter baumannii complex (MRAB)-colonized patients was evaluated using environmental and patient cultures. MRAB occurred in 21% of patients' cultures, 2.1% of 513 areas surrounding MRAB-patients, and one of 372 common areas. No transmission to other patients occurred. Barrier precautions and ethanol disinfection may prevent dissemination.
Brazilian Journal of Infectious Diseases, 2005
OBJECTIVE: Establish the susceptibility pattern of Gram-negative bacteria causing infections in I... more OBJECTIVE: Establish the susceptibility pattern of Gram-negative bacteria causing infections in ICU patients, MYSTIC Program Brazil 2002. MATERIAL AND METHODS: Gram-negative bacteria (n = 503) causing nosocomial infections were collected at seven Brazilian centers. The central laboratory confirmed the identification and performed the susceptibility tests by E-test methodology (AB Biodisk, Solna, Sweden) for meropenem, imipenem, ciprofloxacin, ceftazidime, cefepime, cefotaxime, piperacillin/tazobactam, gentamicin, and tobramycin. Interpretation criteria used were according to National Committee for Clinical Laboratory Standards (NCCLS). RESULTS: Pseudomonas aeruginosa (33%) was the most frequently isolated, followed by A. baumannii (17.1%), K. pneumoniae (12.1%), E. coli (10.5%), and E. cloacae (7.9%). Pseudomonas aeruginosa isolates had susceptibility rates of 67.5% to piperacillin/tazobactam, 59.8% to meropenem, 57.3% to imipenem. A. baumannii presented susceptibility rates to meropenem of 89.5%, 88.4% to imipenem, and 74.4% to tobramycin. E. coli and K. pneumoniae were fully susceptible to both carbapenems. CONCLUSIONS: Carbapenem resistance among Enterobacteriaceae is still rare in this region. A. baumannii and P. aeruginosa presented elevated resistance rates to all antimicrobials. Since these two bacterial species play an important role in nosocomial infections, the use of empirical combination therapy to treat these pathogens may be justified.
Infection Control and Hospital Epidemiology, 1996
A case-control (46 cases, 23 controls) study was done to determine risk factors for an outbreak o... more A case-control (46 cases, 23 controls) study was done to determine risk factors for an outbreak of a multiresistant Acinetobacter baumanii (only susceptible to colistin) in a university hospital. The use of antecedent antibacterials and intubation were independent risk factors. No common source was found. With control measures, the outbreak resolved gradually.
Brazilian Journal of Infectious Diseases, 2003
Telithromycin) is a global surveillance study established in 1999 to monitor antibacterial resist... more Telithromycin) is a global surveillance study established in 1999 to monitor antibacterial resistance of respiratory tract organisms. Thirteen centers from Argentina, Brazil and Mexico participated during 1999-2000; they collected 1,806 isolates (Streptococcus pneumoniae 518, Haemophilus influenzae 520, Moraxella catarrhalis 140, Staphylococcus aureus 351, S. pyogenes 277). Overall, 218 (42.1%) of the S. pneumoniae isolates had reduced susceptibility to penicillin, 79 (15.3%) were penicillin-resistant and 79 (15.3%) were erythromycin-resistant. Mexico had the highest prevalence of penicillin (76.5%) and erythromycin (31.2%) resistance. Of 77 erythromycinresistant S. pneumoniae tested for resistance genotype, 43 possessed mef(A), 33 possessed erm(B) and 1 possessed both erm(B) and mef(A) mechanism. All S. pneumoniae isolates were fully susceptible to telithromycin, linezolid, teicoplanin and vancomycin. Among H. influenzae isolates, 88 (16.9%) produced β
Diagnostic Microbiology and Infectious Disease, 2004
The OPTAMA (Optimizing Pharmacodynamic Target Attainment using the MYSTIC [Meropenem Yearly Susce... more The OPTAMA (Optimizing Pharmacodynamic Target Attainment using the MYSTIC [Meropenem Yearly Susceptibility Test Information Collection] Antibiogram) Program provides insight into the appropriate antibiotic options for empiric therapy for common nosocomial pathogens. In this report, South America is represented by Brazil, Colombia, Peru, and Venezuela. A 5000-subject Monte Carlo Simulation estimated pharmacodynamic target attainment for meropenem, imipenem, ceftazidime, cefepime, piperacillin/tazobactam, and ciprofloxacin against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Pharmacokinetic parameter variability was derived from existing healthy volunteer data, and minimum inhibitory concentration (MIC) data came from the 2002 MYSTIC program. Piperacillin/tazobactam and ciprofloxacin displayed the lowest target attainment against all bacterial species (14% to 24% for A. baumannii, 26% to 37% for P. aeruginosa, and 48% to 66% for the Enterobacteriaceae). Overall, the carbapenems had the highest probabilities of attainment against the Enterobacteriaceae (98% to 100%) and A. baumannii (73% to 74%), whereas cefepime obtained the greatest target attainment against P. aeruginosa (65%). Because no single regimen had high target attainment against A. baumannii and P. aeruginosa, the use of combination therapy to treat these pathogens in South America may be justified. Because of the lack of agreement with percent susceptibility for certain antimicrobial regimens, the use of pharmacodynamic target attainment may be a more accurate predictor of microbiologic success.
Brazilian Journal of Infectious Diseases, 2005
Establish the susceptibility pattern of Gram-negative bacteria causing infections in ICU patients... more Establish the susceptibility pattern of Gram-negative bacteria causing infections in ICU patients, MYSTIC Program Brazil 2003. Gram-negative bacteria (n = 1,550) causing nosocomial infections were collected at 20 Brazilian centers. The central laboratory confirmed the identification and performed the susceptibility tests by Etest methodology (AB Biodisk, Solna, Sweden) for meropenem, imipenem, ciprofloxacin, ceftazidime, cefepime, cefotaxime, piperacillin/tazobactam, gentamicin, and tobramycin. Interpretation criteria used were according to National Committee for Clinical Laboratory Standards (NCCLS). Pseudomonas aeruginosa (30.3%) was the most frequent isolate, followed by E. coli (18.6%), Klebsiella pneumoniae (16.9%), Acitenobacter baumannii (8.8%), and Enterobacter cloacae (7.1%). Pseudomonas aeruginosa (n=470) isolates presented susceptibility rates of 64% to meropenem, 63.8% to piperacillin/tazobactam, 63.4% to amikacin, 58.7% to imipenem. Acitenobacter baumannii presented susceptibility rates to meropenem of 97.1%, and 73% to tobramycin. E. coli and K. pneumoniae were highly susceptible to both carbapenems.Carbapenem resistance among the Enterobacteriaceae is still rare in the region. Acitenobacter baumannii and P. aeruginosa presented elevated resistance rates to all antimicrobials. Since they play an important role in nosocomial infections in this environment, the use of empirical combination therapy to treat these pathogens may be justified.
Infection Control and Hospital Epidemiology, 1999
A case-control study was done to evaluate factors associated with nosocomial infections by multir... more A case-control study was done to evaluate factors associated with nosocomial infections by multiresistant Pseudomonas aeruginosa (MRPA). Results showed that MRPA was associated with the use of immunosuppressive and antimicrobial drugs. Five typing methods indicated that the MRPA infections were due to multiple strains rather than a single strain.
Brazilian Journal of Infectious Diseases, 2001
Surveillance programs are essential to detect the increase of antimicrobial resistance, and sever... more Surveillance programs are essential to detect the increase of antimicrobial resistance, and several different programs are being conducted in many countries. The RESISTNET is a surveillance program for bacterial resistance against several antimicrobial agents initiated in 1998 among Latin American countries. In Brazil, several centers were invited to join this surveillance and a total of 11 centers (6 from São Paulo and 5 from other states) participated in the study. All results were analyzed using the WHONET program. A total of 894 Escherichia coli, 386 Klebsiella pneumoniae, 70 Shigella spp and 57 Salmonella spp strains were analyzed in this study from April, 1998, to April, 1999. Susceptibility testing was performed by the disk diffusion method using NCCLS 1998 guidelines for several different drugs. For all strains, imipenem was the most effective drug (100% of the strains were susceptible). Klebsiella pneumoniae presented a high resistance rate to ampicillin (96.4%). The rate of probable ESBL producers among K. pneumoniae strains was 36.3%, most of them being isolated from catheters (58.8%). Among all Escherichia coli strains analyzed, the highest resistance rate was found for trimethoprim/sulfamethoxazole (46.9%) and the majority of the resistant strains were isolated from urine samples (47.8%). Among Salmonella spp, the resistance rates were low for all antibiotics tested. For Shigella spp strains there was a high resistance to trimethoprim/sulfamethoxazole (80.0%). No resistance to ceftriaxone was observed in these strains. Surveillance of antimicrobial resistance is critical for the successful management of infectious diseases. The results of this survey show significant resistance rates among these bacteria which are responsible for several types of human infections.
Diagnostic Microbiology and Infectious Disease, 2005
Meropenem and imipenem are often the drugs of choice for the treatment of infections due to multi... more Meropenem and imipenem are often the drugs of choice for the treatment of infections due to multidrug-resistant Acinetobacter baumannii. The present study aimed at evaluating the interaction between meropenem and sulbactam through microdilution and checkerboard methods against 48 clinical isolates of A. baumannii collected from Brazilian hospitals. All the isolates presented elevated minimum inhibitory concentration (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=2 microg/mL) to either meropenem or sulbactam. The checkerboard method with the combination of meropenem and sulbactam demonstrated 29.2% (14/48) synergism, 47.9% (23/48) partial synergism, 10.5% (5/48) additive, 6.2% (3/48) indifference, and 6.2% (3/48) antagonism (SigmaFIC(min)=0.09 and SigmaFIC(max)=8). Thus, combinations of meropenem and sulbactam may show synergism or partial synergism for most A. baumannii isolates. Further studies may help identify treatment options for patients with infections caused by these organisms, particularly with this combination, where both drugs have time-dependent activities and might be suitable for therapy optimization studies.
International Journal of Antimicrobial Agents, 2006
The pharmacodynamic potency of imipenem, meropenem and ertapenem against extended-spectrum -lact... more The pharmacodynamic potency of imipenem, meropenem and ertapenem against extended-spectrum -lactamase (ESBL)-producing isolates was investigated. Minimal inhibitory concentration (MIC) determination, confirmation of ESBLs by Etest and the disk approximation test were performed for 133 ESBL-producing isolates of Escherichia coli and Klebsiella spp. Pharmacodynamic exposure, measured as percent of the dosing interval during which free drug was above the MIC (% fT > MIC), was modelled via a 5000-subject Monte Carlo simulation. Bactericidal cumulative fraction of response (CFR), defined as 40% fT > MIC, was calculated against each bacterial population. All agents achieved high bactericidal CFR against all ESBL isolates as a group, but ertapenem (96.26%) was slightly less effective than imipenem (99.96%) and meropenem (99.90%) (P < 0.05). Similar results were observed against Klebsiella spp. only (P < 0.05). Against E. coli, CFRs were close to 100%. Ertapenem is probably an effective agent against ESBL-producing bacteria, although its ability to achieve bactericidal pharmacodynamic exposures will depend on the bacterial susceptibility.
Diagnostic Microbiology and Infectious Disease, 2005
This overview provides a summary of the Meropenem Yearly Susceptibility Test Information Collecti... more This overview provides a summary of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program over an 8-year period from 1997 to 2004. The evolution of the MYSTIC Program is described, as well as its design compared with other surveillance programs. In addition, the global MYSTIC Program data, published to date, are summarized, and the empiric use of carbapenems, their current indications, and meropenem usage versus resistance was discussed. From 1997 to 2004, 120 medical centers that were actively prescribing meropenem in 32 countries worldwide participated in the program. The MYSTIC Program results demonstrate the sustained potency and continued effectiveness of meropenem globally against clinically relevant Gram-negative and Gram-positive pathogens including extended spectrum beta-lactamase- and AmpC beta-lactamase-producing organisms, which may also display resistance to the fluoroquinolones and/or aminoglycosides. Furthermore, in centers actively prescribing meropenem, resistance to meropenem is not increasing despite greater resistance among the comparator antimicrobial agents. Thus, antipseudomonal carbapenems such as meropenem and imipenem remain an effective treatment option.