Rates of serum level determinations of antiepileptic drugs in accord with guidelines: A clinical study at a tertiary center.

OBJECTIVE: To compare our rates of appropriate therapeutic drug monitoring (TDM) with those defined in the French guidelines for measuring drug levels of antiepileptic drugs (AEDs) during the pre- and post-medical/pharmaceutical interventional periods. METHODS: This study was prospectively carried out at a tertiary center (epilepsy unit of the Pitié-Salpêtrière Hospital in Paris) between 2013 and 2016 over three time periods. Criteria for appropriateness were those stated in the current French guidelines. The main outcome measure was the percentage of drug level measurements with an appropriate indication, while a second outcome measure was the impact of education on clinical practice. RESULTS: Of the 698 AED level measurements requested, 84% overall were found to have appropriate indications ranging from 75% to 90%, according to French guideline criteria. Rates of appropriate indications for the three most commonly used individual AEDs-valproate, carbamazepine and lamotrigine-were 79.6%, 77.3% and 90.7%, respectively, whereas the requests considered to not have an appropriate indication involved the majority (63.5%) of cases of routine drug monitoring. In addition, dedicated education seems to substantially increase rates of appropriateness. CONCLUSION: At our center, 84% of AED level determinations had an appropriate indication according to a priori defined and reliable criteria. Moreover, it was noted that a specific educational intervention substantially increased rates of appropriateness. Thus, it appears to be crucial to ensure that medical and paramedical staff are aware of the official recommendations to avoid taking unnecessary drug level measurements.

Low interleukin-10 production by monocytes of patients with a self-limiting hepatitis C virus infection.

Host factors seem to be crucial for the spontaneous clearance of hepatitis C virus (HCV). Monocytes play a pivotal role in innate immunity and help regulate adaptive responses. This study assesses the characteristics of monocytes from patients with self-limiting HCV infections. We studied 35 consecutive patients [11 with a self-limiting HCV infection, 16 chronically infected with HCV and sustained virological responders (SVR) following antiviral therapy, and eight chronically infected HCV but untreated] and eight healthy donors (HD). The production of interleukin (IL)-10, tumour necrosis factor-alpha (TNF-alpha) and IL-12p40 by monocytes stimulated with lipopolysaccharides(LPS) or HCV Core protein was measured by enzyme-linked immunoassay. Monocyte surface markers were analysed by flow cytometry. LPS and Core protein triggered IL-10 and TNF-alpha production, but monocytes from self-limiting infection patients produced significantly less IL-10 and TNF-alpha than those of SVR, chronically infected or HD (P < 0.05), while IL-12p40 production was unchanged. This cytokine production profile did not appear to be due to expansion of the CD14(+) CD16(+) monocyte subset or to a classical or alternative activation monocyte profile. Monocytes from self-limiting infection patients had more CCR7 than those from SVR or chronically infected patients (P < 0.05). Monocytes of self-limiting infection patients appear to produce little IL-10 and TNF-alpha in response to viral or unspecific stimulation and to have a higher CCR7 expression. This profile seems to be independent to a particular monocyte subset or activation state. Low IL-10 production may help establish an effective immune response and spontaneous HCV clearance.

Clonal spread of carbapenem-resistant Acinetobacter baumannii in a neonatal intensive care unit.

Acinetobacter baumannii has often been associated with colonization and/or infection in neonatal intensive care units (NICU). This study describes a clonal spread of carbapenem-resistant A. baumannii (CRAB) isolates in an NICU. In total, 21 CRAB isolates were collected from premature newborns. Only polymyxin B was active against such isolates. Nineteen CRAB isolates were clonally related (Cluster C, which belonged to worldwide-disseminated ST1). All newborns had peripheral access and had received ß-lactam therapy previously. The implementation of strict infection control measures was of fundamental importance to eradicate the clonal type in the study hospital.

An outbreak of catalase-negative methicillin-resistant Staphylococcus aureus.

The wide dissemination of a major epidemic methicillin-resistant Staphylococcus aureus (MRSA) clone in Brazilian hospitals (Brazilian clone) limits the value of molecular typing techniques such as pulsed-field gel electrophoresis (PFGE) for outbreak investigation. We report the first outbreak of a catalase-negative strain of MRSA, which was initially detected by the unusual result of this phenotypical test. The outbreak occurred in the Hospital Sanatorinhos de Carapicuíba, a 237-bed secondary hospital located in São Paulo, Brazil. From May to August 2002, a total of 11 MRSA isolates were recovered from four patients in the intensive care unit. All the isolates were catalase negative and susceptible only to vancomycin and linezolid. Three of the four patients eventually died. Molecular typing demonstrated an indistinguishable PFGE pattern among the 11 isolates, with similarities to the Brazilian clone and the hospital's usual MRSA strain. This report emphasizes the importance of an uncommon phenotypical result as a marker for initiating an outbreak investigation and should encourage clinical laboratories to recognize and report such isolates.

Global assessment of the antimicrobial activity of polymyxin B against 54 731 clinical isolates of Gram-negative bacilli: report from the SENTRY antimicrobial surveillance programme (2001-2004).

In total, 54 731 Gram-negative bacilli isolated worldwide between 2001 and 2004 from diverse sites of infection were tested for susceptibility to polymyxin B by the broth reference microdilution method, with interpretation of results according to CLSI (formerly NCCLS) guidelines. Polymyxin B showed excellent potency and spectrum against 8705 Pseudomonas aeruginosa and 2621 Acinetobacter spp. isolates (MIC50, < or = 1 mg/L and MIC90, 2 mg/L for both pathogens). Polymyxin B resistance rates were slightly higher for carbapenem-resistant P. aeruginosa (2.7%) and Acinetobacter spp. (2.8%), or multidrug-resistant (MDR) P. aeruginosa (3.3%) and Acinetobacter spp. (3.2%), when compared with the entire group (1.3% for P. aeruginosa and 2.1% for Acinetobacter spp.). Among P. aeruginosa, polymyxin B resistance rates varied from 2.9% in the Asia-Pacific region to only 1.1% in Europe, Latin America and North America, while polymyxin B resistance rates ranged from 2.7% in Europe to 1.7% in North America and Latin America among Acinetobacter spp. Polymyxin B also demonstrated excellent activity (MIC90, < or = 1 mg/L; > 98% susceptible) against Citrobacter spp., Escherichia coli and Klebsiella spp., but activity was more variable against Enterobacter spp. (MIC50, < or = 1 mg/L; 83.3% susceptible) and Stenotrophomonas maltophilia (MIC50, < or = 1 mg/L; 72.4% susceptible), and was very limited (MIC50, > 8 mg/L) against Burkholderia cepacia (11.8% susceptible), Serratia spp. (5.4% susceptible), indole-positive Proteus spp. (1.3% susceptible) and Proteus mirabilis (0.7% susceptible).

Antimicrobial activity of dalbavancin tested against Gram-positive clinical isolates from Latin American medical centres.

The activity of dalbavancin, a new semi-synthetic lipoglycopeptide antibiotic, was evaluated in comparison with other antibacterial agents against 1229 Gram-positive organisms collected from medical centres in Latin America. Dalbavancin was the most potent compound tested against isolates of Staphylococcus aureus (MIC(50), 0.06 mg/L) and coagulase-negative staphylococci (MIC(50), 0.03 mg/L), independently of methicillin susceptibility. Dalbavancin inhibited all Streptococcus pneumoniae isolates at /= 8 mg/L. Dalbavancin exhibited excellent activity against isolates of Corynebacterium spp. and Listeria spp. Dalbavancin may provide an important therapeutic option for Gram-positive infections, excluding those caused by enterococci with VanA-type resistance.

IMPs, VIMs and SPMs: the diversity of metallo-beta-lactamases produced by carbapenem-resistant Pseudomonas aeruginosa in a Brazilian hospital.

Pseudomonas aeruginosa isolates (n=183), collected from bacteraemic patients hospitalised in Sao Paulo Hospital (Brazil) during 2000-2001, were screened for susceptibility to antimicrobial agents. The polymyxins were the most active compounds (100% susceptibility), followed by amikacin and cefepime (59.0%), meropenem (57.4%), and imipenem and gentamicin (55.2%). Imipenem-resistant isolates were ribotyped and screened for production of metallo-beta-lactamases (MBLs) by PCR with primers for bla(IMP), bla(VIM) and bla(SPM). MBL production was detected in 36 isolates (19.7% of the entire collection; 43.9% of the imipenem-resistant isolates) and the MBLs included SPM-1-like (55.6%), VIM-2-like (30.6%) and IMP-1-like (8.3%) enzymes.

Unusual association of NDM-1 with KPC-2 and armA among Brazilian Enterobacteriaceae isolates.

We report the microbiological characterization of four New Delhi metallo-ß-lactamase-1 (blaNDM-1)-producing Enterobacteriaceae isolated in Rio de Janeiro, Brazil. blaNDM-1 was located on a conjugative plasmid and was associated with Klebsiella pneumoniae carbapenemase-2 (blaKPC-2) or aminoglycoside-resistance methylase (armA), a 16S rRNA methylase not previously reported in Brazil, in two distinct strains of Enterobacter cloacae. Our results suggested that the introduction of blaNDM-1 in Brazil has been accompanied by rapid spread, since our isolates showed no genetic relationship.

Survival of vancomycin-intermediate Staphylococcus aureus on hospital surfaces.

BACKGROUND: Contaminated surfaces play an important role in the transmission of certain pathogens that are responsible for healthcare-associated infections. Although previous studies have shown that meticillin-resistant Staphylococcus aureus (MRSA) can survive on dry surfaces at room temperature, no published data regarding vancomycin-intermediate S. aureus (VISA) are available to date. AIM: To compare the survival time on different types of surfaces, cell-surface hydrophobicity, adherence to abiotic surfaces and biofilm formation of meticillin-susceptible S. aureus (MSSA), MRSA and VISA. METHODS: Survival of the S. aureus strains was tested on latex, cotton fabric, vinyl flooring and formica. Cell-surface hydrophobicity was determined using the hydrocarbon interaction affinity method. Adhesion to abiotic surfaces was tested on granite, latex (gloves), glass, vinyl flooring and formica. Biofilm formation was evaluated at 6, 12, 24 and 48 h. FINDINGS: All of the samples survived on the vinyl flooring and formica for at least 40 days. VISA survived on both surfaces for more than 45 days. All of the strains were highly hydrophobic. VISA adhered to latex, vinyl flooring and formica. Biofilm formation increased for all of the tested strains within 6-24 h. CONCLUSION: VISA present high survival, adherence and cell-surface hydrophobicity. Therefore, as the treatment of patients with VISA is a significant challenge for clinicians, greater care with cleaning and disinfection of different types of surfaces in healthcare facilities is recommended because these may become important reservoirs of multi-resistant pathogens.

Emerging strategies in infectious diseases: new carbapenem and trinem antibacterial agents.

Beta-lactam antibiotics represent the most commonly prescribed antibacterial agents. New beta-lactams have been introduced continuously as many bacteria have developed resistance to older agents. In the late 1970s, a new class of exceptionally broad spectrum beta-lactams, the carbapenems, was identified. Despite being a very potent compound, the antibacterial activity of the first carbapenem, imipenem, was compromised because of hydrolysis by the renal dehydropeptidase enzyme (DHP-1), and it is now coadministered with a potent competitive inhibitor of the DHP-1 enzyme, cilastin. Molecular modifications in the carbapenem nucleus were able to increase stability to DHP-1 and retain the antibacterial activity. However, some important pathogenic bacteria were found to be resistant to this new class of agents. In addition, other clinically important gram-negative species, such as Pseudomonas aeruginosa, developed resistance mainly by the production of potent beta-lactamases and reduced permeability of the outer membrane. Since the discovery of imipenem/cilastatin, a great number of carbapenems have been developed, and a few of them have been marketed. Stability to hydrolysis by DHP-1 and decrease in toxicity were achieved by meropenem and biapenem. However, only a slight increase in the antibacterial potency and spectrum has been accomplished with either the new marketed or experimental parenteral compounds. In addition, compounds that can be administered orally, such as the carbapenens faropenem, CS-834 and MK-826, and the trinem sanfetrinem, have been developed. However, when compared with the parenterally administered compounds, the oral agents seem to lose some in vitro antibacterial activity, especially against P. aeruginosa.

Antimicrobial activity and spectrum of the new glycylcycline, GAR-936 tested against 1,203 recent clinical bacterial isolates.

The in vitro activity of GAR-936, a new semisynthetic glycylcycline, was evaluated in comparison with two tetracyclines and several other antimicrobial agents. A total of 1,203 recent clinical isolates were tested by reference broth or agar dilution methods. Among the members of the family Enterobacteriaceae, GAR-936 was generally two- to four-fold more active than minocycline, and two- to 16-fold more active than tetracycline. All enteric bacilli MIC90 results were < or = 4 microg/mL; the exception being Proteus mirabilis and indole-positive Proteae (> or = 8 microg/mL). GAR-936 demonstrated excellent activity against all gram-positive cocci with 90% of the penicillin-resistant Streptococcus pneumoniae isolates inhibited at 0.03 microg/ml, while the same isolates had a MIC90 of 8 and > 8 microg/mL for minocycline and tetracycline, respectively. All Enterococcus spp., including vancomycin-resistant isolates, were inhibited at 0.25 microg/mL of GAR-936 (MIC90, 0.12 or 0.25 microg/mL). Although GAR-936 (MIC50, 0.25 microg/mL) was two-fold less active than minocycline (MIC50, 0.12 microg/mL) against oxacillin-resistant Staphylococcus aureus, all isolates were inhibited at < or = 0.25 microg/mL. GAR-936 demonstrated good activity against nonfermentative bacteria such as Acinetobacter spp. (MIC90, 2 microg/ml) and Stenotrophomonas maltophilia (MIC90, 4 microg/mL), but the compound exhibited only modest activity against Pseudomonas aeruginosa (MIC50, 8 microg/mL). Haemophilus influenzae (MIC90, 1-2 microg/mL), Moraxella catarrhalis (MIC90, 0.12 microg/mL), and various Neisseria spp. (MIC90, 0.12-0.5 microg/mL) were susceptible to GAR-936. These results indicate that GAR-936 has potent in vitro activity against a wide range of clinically important pathogenic bacteria, and that several gram-positive and -negative isolates resistant to older tetracyclines and other drug classes remain susceptible to GAR-936, the newest glycylcycline candidate for clinical use.

Occurrence of single-point gyrA mutations among ciprofloxacin-susceptible Escherichia coli isolates causing urinary tract infections in Latin America.

To detect if isolates susceptible to quinolones already carry mutations in the gyrA and parC genes, we selected 12 ciprofloxacin-susceptible Escherichia coli strains collected from patients with urinary tract infections in Latin America in 1998, as part of ongoing SENTRY Antimicrobial Surveillance Program. The isolates studied exhibited minimal inhibitory concentrations (MICs) for ciprofloxacin between < or = 0.015 microg/mL and 0.5 microg/mL. The molecular characterization of quinolone resistance was determinated by amplification of the gyrA and parC by PCR followed by sequencing of the respective amplicons. We observed that E. coli isolates exhibiting MIC, < or = 0.06 microg/mL for ciprofloxacin did not show mutations in either topoisomerase. On the other hand, all isolates with MIC between 0.12 microg/mL and 0.5 microg/mL demonstrated single mutation in the gyrA gene. The most frequent mutation occurred at position 83, where the amino acid serine was replaced by leucine. No mutations in the parC gene were observed. To preserve the potency and prevent the development of resistance, we suggest that quinolone usage should be rational, especially in the treatment of urinary tract infections, and in the prophylaxis of immunosupressed patient populations.

Frequency of occurrence and antimicrobial susceptibility patterns for pathogens isolated from latin american patients with a diagnosis of pneumonia: results from the SENTRY antimicrobial surveillance program (1998).

The correct empiric choice of antimicrobial therapy in the treatment of pneumonia in hospitalized patients has established itself as a major therapeutic challenge to clinicians. Selection of an inappropriate antimicrobial agent could lead to increased rates of mortality and morbidity. Characteristics of pathogens responsible for this infection such as species prevalence, overall antimicrobial resistance rates, and mechanisms of detected resistance could serve as an invaluable resource to clinicians in making such therapeutic selections. This report addresses the aforementioned problems/needs by analysis of 712 strains isolated from the lower respiratory tract of patients hospitalized with a diagnosis of pneumonia in 10 Latin American medical centers in the SENTRY Antimicrobial Surveillance Program (1998). The four most frequently isolated pathogens (no/% of total) were: Pseudomonas aeruginosa (191/26.8%), Staphylococcus aureus (171/24.0%), Klebsiella spp. (86/12.1%), and Acinetobacter spp. (75/10.5%); representing nearly 75.0% of all isolates. More than 40 antimicrobial agents (23 reported) were tested against these isolates by reference broth microdilution methodology, and susceptibility profiles were established. The nonfermentative Gram-negative bacteria (P. aeruginosa and Acinetobacter spp.) exhibited high levels of resistance to the agents tested. Amikacin (77.5% susceptible) was the most active drug tested against P. aeruginosa 50.0% against the Acinetobacter spp. isolates. Based on published interpretive criteria, over 22.0% of the Klebsiella spp. and 12.5% of the Escherichia coli were classified as extended spectrum beta-lactamase (ESBL) producers. Of the cephalosporin class compounds tested against the Klebsiella spp. and E. coli isolates, cefepime demonstrated the highest rates of susceptibility (84.9% and 91.7%, respectively). This compound also fared well against the Enterobacter spp. isolates, inhibiting 88.2% of the isolates tested, many of which were resistant to ceftazidime and ceftriaxone. Resistance to oxacillin among the S. aureus isolates was nearly 50. 0%, with vancomycin, teicoplanin, and the streptogramin combination quinupristin/dalfopristin inhibiting all isolates. Several clusters of multiply resistant organisms were also observed, and further characterization by ribotyping and pulsed-field gel electrophoresis established possible patient-to-patient spread. The results of this study indicate that rates of resistance among respiratory tract pathogens continue to rise in Latin America, with specific concerns for the high prevalence of nonfermentative Gram-negative bacteria isolated, oxacillin resistance rates in S. aureus, and the epidemic dissemination of multiply-resistant strains in several medical centers. International surveillance programs (SENTRY) should assist in the control of escalating antimicrobial resistance in this geographic area.

Evaluation of the in vitro activity of six broad-spectrum beta-lactam antimicrobial agents tested against over 2,000 clinical isolates from 22 medical centers in Japan. Japan Antimicrobial Resistance Study Group.

Numerous broad-spectrum beta-lactam antimicrobial agents have been introduced into medical practice since 1985. Although several of these compounds have advanced, infectious disease therapy resistances to them has also emerged world-wide. In 1997, a Japanese 22 medical center investigation was initiated to assess the continued utility of these agents (oxacillin or piperacillin, ceftazidime, cefepime, cefpirome, cefoperazone/sulbactam [C/S], imipenem). The participating medical centers represented a wide geographic distribution, and a common protocol and reagents were applied. Three control strains and a set of challenge organisms were provided to participant centers. Etest (AB BIODISK, Solna, Sweden) strips were used in concurrent tests of these organisms and a qualitative determination of participant skills in the identification of resistant and susceptible phenotypes was established. The quantitative controls demonstrated 97.7-99.2% of MIC values within established QC limits, and the qualitative (susceptibility category) controls documented a 97.3% agreement of participant results with that of reference values (1,320 total results). Only 0.2% of values were false-susceptible errors. After the participant quality was assured, a total of 2,015 clinical strains were tested (10 strains from 10 different organism groups including methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci [CoNS], Escherichia coli, Klebsiella spp., Citrobacter freundii, Enterobacter spp., indole-positive Proteae, Serratia spp., Acinetobacter spp., and Pseudomonas aeruginosa). The staphylococci were uniformly susceptible to all drugs tested except ceftazidime (MIC90, 24 micrograms/ml) that had a potency six- to 12-fold less than either cefepime or cefpirome. Only 3.7 and 45.1% of S. aureus and CoNS were susceptible to ceftazidime, respectively. Among E. coli and Klebsiella spp. the rank order of antimicrobial spectrum was imipenem = "fourth-generation" cephalosporins > ceftazidime > C/S > piperacillin. Possible extended spectrum beta-lactamase phenotypes were identified in 2.9-8.6% of these isolates. Isolates of C. freundii, Enterobacter spp., Proteae, and Serratia spp. that were resistant to ceftazidime and piperacillin remained susceptible to imipenem (0.0-4.5% resistance) and cefepime (0.0-5.0%). Acinetobacters were inhibited best by C/S (99.5% susceptible) and least susceptible to piperacillin (MIC90, > 256 micrograms/ml; 21.7% susceptible) activity. P. aeruginosa isolates were most susceptible to cefepime (83.6%) and this zwitterionic cephalosporin also had the lowest level of resistance (9.1% of MICs at > or = 32 micrograms/ml). Several multi-resistant organisms were identified in participant medical centers including S. marcescens strains resistant to cefepime, imipenem, or both observed in six hospitals. Clonal spread was documented in two medical centers; one hospital having two distinct epidemic clusters. Also a multi-resistant E. cloacae was found in two patients in the same hospital. Evaluations of carbapenem resistance in four species discovered only two strains (in same hospital) among 40 P. aeruginosa isolates (5.0%) with a metallo-enzyme, with nearly all of the remaining strains inhibited by an Ambler Class C enzyme inhibitor (BRL42715) indicating a hyperproduction of a chromosomal cephalosporinase. These results indicate that most newer beta-lactams remain widely useable in medical centers in Japan, but emerging often clonal, resistances have occurred. The overall rank order of antimicrobial spectrum against all ten tested bacterial groups favors the "fourth-generation" cephalosporin, cefepime (96.4% susceptible) as an equal to imipenem (95.9%) > C/S (90.9%) = cefpirome (90.0%) > ceftazidime (75.1%) = penicillins, either oxacillin or piperacillin (76.4%).

Carbapenem-resistant Serratia marcescens isolates producing Bush group 2f beta-lactamase (SME-1) in the United States: results from the MYSTIC Programme.

Two carbapenem (imipenem, meropenem)-resistant Serratia marcescens strains were isolated in the United States (Chicago, IL) through the 1999 MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) Programme. The S. marcescens antimicrobial susceptible patterns were: susceptible to ceftriaxone, ceftazidime, and cefepime (MICs, < or = 0.25 microg/ml), and resistance to the carbapenems (imipenem and meropenem; MIC, > 32 microg/ml) and aztreonam (MIC, > = 16 microg/ml). Each S. marcescens isolate shared an identical epidemiologic type (ribotype and PFGE) and the outer membrane protein profile was also identical to those of the wild type susceptible strains from the same medical center. The PCR utilizing bla(sme-1) primers amplified a gene product that was identified as consistent with SME-1 after DNA sequencing. Imipenem and meropenem resistance due to production of carbapenem-hydrolyzing enzymes among clinical isolates is still very rare, but microbiology laboratories should be aware of these chromosomally encoded enzymes among class C beta-lactamases producing enteric bacilli such as S. marcescens and Enterobacter cloacae.

Antimicrobial susceptibility patterns for pathogens isolated from patients in Latin American medical centers with a diagnosis of pneumonia: analysis of results from the SENTRY Antimicrobial Surveillance Program (1997). SENTRY Latin America Study Group.

Pneumonia is the most common fatal hospital-acquired infection, with attributable mortality rates ranging from 30 to 60%. Rapid initiation of optimal antimicrobial therapy is essential for obtaining treatment success. In this report the antimicrobial susceptibility of 556 strains from the lower respiratory tract were collected by the SENTRY Antimicrobial Surveillance Program (1997). These strains were isolated from hospitalized patients with pneumonia in 10 Latin American centers (6 countries) as part of this 68-center worldwide program. The isolates were susceptibility tested against more than 70 drugs (35 reported) by the reference broth microdilution method. Klebsiella pneumoniae and Escherichia coli phenotypically consistent with extended spectrum beta-lactamase (ESBL) production were characterized further by ribotyping and pulsed-field gel electrophoresis. The five most frequently isolated species were (n/%): Pseudomonas aeruginosa (149/26.8%), Staphylococcus aureus (127/22.8%), Acinetobacter spp. (66/11.9%), Klebsiella spp. (56/10.1%), and Enterobacter spp. (40/7.2%). P. aeruginosa demonstrated high rates of resistance to a majority of the antimicrobial drugs tested. Carbapenems, amikacin, and piperacillin/tazobactam demonstrated the highest susceptibility rates (73.8-77.2%) against P. aeruginosa, however the lowest resistance rate was observed for cefepime (6.7%). Acinetobacter spp. also showed very high rates of resistance and the most active compounds were imipenem and meropenem (89.0% susceptibility) followed by the tetracyclines. Cephalosporin susceptibilities among Klebsiella spp. were low: cefoxitin, 73.0%; ceftazidime, 69.4%; and ceftriaxone, 65.9%. Approximately 37% and 28% of K. pneumoniae and E. coli isolates, respectively, were considered ESBL producers based on NCCLS criteria. Ceftriaxone was active against only 52.5% of Enterobacter spp. isolates, whereas cefepime was active against 90.0% of isolates (MIC50, < or = 0.12 microgram/mL). Oxacillin resistance was detected in nearly 50% of S. aureus isolates. The most active drugs against S. aureus were vancomycin, teicoplanin, and quinupristin/dalfopristin (MIC90, 1 microgram/mL). In summary, our study of pneumonias in Latin American medical centers demonstrated a greatly increased prevalence of Acinetobacter spp. and higher resistance rates among Gram-negative bacilli when compared with similar controlled studies from North America.

Antimicrobial susceptibility of Streptococcus pneumoniae in Latin America: results from five years of the SENTRY Antimicrobial Surveillance Program.

A total of 1561 pneumococcal isolates were collected in 1997-2001, mainly from patients with community-acquired respiratory tract infections, and susceptibilities were tested by reference broth microdilution against 29 antimicrobial agents. In general, 69.3% of strains were considered susceptible (MIC < or = 0.06 mg/L) to penicillin. Resistance to penicillin (MIC > or = 2 mg/L) and cefotaxime (MIC > or = 4 mg/L) was found in 11.9% and 0.4% of isolates, respectively. The fluoroquinolones gatifloxacin (MIC90, 0.5 mg/L) and levofloxacin (MIC90, 1 mg/L) were active against > 99% of the isolates tested. Among the other non-beta-lactam drugs tested, the rank order of susceptibility was chloramphenicol (95.6%) > clindamycin (94.5%) > azithromycin (88.5%) > clarithromycin (87.5%) >tetracycline (79.5%) > trimethoprim + sulphamethoxazole (60.5%). The penicillin-non-susceptible isolates presented higher rates of resistance to other antimicrobial agents. The rank order of penicillin resistance rates among the seven participating countries was Mexico (25.0%) > Uruguay (19.2%) > Chile (18.3%) > Colombia = Argentina (9.9%) > Brazil (3.9%) > Venezuela (2.8%). The regional rate of penicillin resistance did not vary significantly over the years studied (p 0.339). Screening for the ermB and mefA genes by multiplex rapid cycle PCR on 23 erythromycin-resistant isolates collected during the year 2001 showed that 43.5% and 56.5%, respectively, were positive for ermB and mefA. Overall, the results indicated that antimicrobial susceptibilities of Streptococcus pneumoniae vary significantly among Latin American countries. Regional and local surveillance programmes are necessary to guide empirical therapy of pneumococcal infection in Latin American countries.

GAR-936 (9-t-butylglycylamido-minocycline) susceptibility test development for streptococci, Haemophilus influenzae and Neisseria gonorrhoeae: preliminary guidelines and interpretive criteria.

GAR-936, a new semisynthetic derivative of minocycline, has earlier shown promising activity against tetracycline-resistant pathogens, including Streptococcus pneumoniae. In this study, the activity of GAR-936 was tested against a total of 514 tetracycline-susceptible and -resistant strains of S. pneumoniae, beta-haemolytic streptococci, viridans group streptococci, Haemophilus influenzae and Neisseria gonorrhoeae. All strains of H. influenzae, were inhibited by < or =2 mg/l of GAR-936, with MIC(90)s for all streptococci and gonococci of < or =0.5 mg/l. Scattergrams of GAR-936 comparing MICs by broth microdilution testing and zone diameters using 30 microg disks, confirmed the proposed susceptibility criteria of < or 2 mg/l or > or =20 mm zone diameter. Clinical trial results should be correlated with these preliminary in vitro results to confirm and/or adjust these susceptibility interpretive criteria for GAR-936 when testing fastidious streptococci, H. influenzae and N. gonorrhoeae.