In Vitro Activity of Cefdinir against Respiratory Pathogens Isolated in Sicily with Reference to Beta-Lactamase Production

Abstract

The In Vitro activity of cefdinir (CI-983, FK-482), an orally absorbed aminothiazolyl cephalosporin, was evaluated against all 287 strains of Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Streptococcus pneumoniae and Streptococcus pyogenes in comparison with cefaclor, cefuroxime, amoxicillin, amoxicillin-clavulanic acid, erythromycin and cotrimoxazole.

The bactericidal activity of cefdinir, cotrimoxazole, amoxicillin-clavulanic acid and erythromycin was determined against H. influenzae, M. catarrhalis and S. pneumoniae. With the exception of one beta-lactamase negative ampicillin-resistant strain of H. influenzae (resistant to all antibiotics tested), no resistance to cefdinir was observed (MIC≤1 mg/l). Cefdinir was active against H. influenzae, H. parainfluenzae and M. catarrhalis regardless of whether or not they produced beta-lactamase. In general, the inhibitory concentrations of cefdinir against H. influenzae, H. parainfluenzae and M. catarrhalis were similar to those of amoxicillin/clavulanic acid, one or two dilutions lower than those of cefuroxime and four dilu tions lower than those of cefaclor and cotrimoxazole. Against S. pneumoniae and S. pyogenes cefdinir had the same activity as cefuroxime and amoxicillin but was more effective than the other antibiotics tested.

Kinetic studies showed that cefdinir was rapidly bactericidal at concentrations 2 and 4 times the minimum inhibitory concentration (MIC): a reduction of 99.9% in CFU values was generally observed after 6-8 h.     

Comparative In Vitro Activity of Telithromycin and β-Lactam Antimicrobials Against Bacterial Pathogens from Community-Acquired Respiratory Tract Infections: Data from the First Year of PROTEKT (1999-2000)

Abstract

The In Vitro activity of telithromycin, a new ketolide, was compared with β-lactam antimicrobials against pathogens commonly associated with community-acquired respiratory tract infections. These pathogens were collected during 1999-2000 as part of the ongoing PROTEKT surveillance study. Globally, penicillin non-susceptibility among Streptococcus pneumoniae (n=3362) was 36.3%, ranging from 21.5% (Australasia) to 68.0% (Far East). Telithromycin showed higher potency (MIC₉₀ 0.12 mg/L) than β-lactams against S. pneumoniae; 99.9% of all and 99.6% of multi-resistant isolates were susceptible to telithromycin. Among Streptococcus pyogenes isolates (n=1485), 100% were susceptible to β-lactams, and the telithromycin MIC₅₀ and MIC₉₀ were both 0.015 mg/L. Among Haemophilus influenzae (n=2948), 16.6% produced β-lactamase, which reduced the activity of ampicillin, cefaclor and cefprozil. 99.9% of H. influenzae were susceptible to telithromycin and the MIC range for M. catarrhalis was 0.004-0.5 mg/L. The first year results of PROTEKT confirmed high potency for telithromycin against common respiratory tract pathogens, including β-lactam-resistant strains.     

Antibiotic Susceptibility of Respiratory Pathogens Recently Isolated in Italy: Focus on Cefditoren

Abstract

The aim of this study was to evaluate the in vitro antibiotic susceptibility of respiratory pathogens recently isolated in italy to commonly used antibiotics including cefditoren. Six clinical microbiological laboratories collected, between January and September 2009, a total of 2,510 respiratory pathogens from subjects with community- acquired respiratory tract infections (CARTI). Cefditoren, out of all the beta-lactams studied, had the lowest MIC₉₀ against 965 strains of Streptococcus pneumoniae examined, followed by cefotaxime and ceftriaxone (2% resistance in penicillin-resistant S. pneumoniae (PRSP)). Against 470 Haemophilus influenzae, independently of their production of beta-lactamases or ampicillin resistance, cefditoren was the oral cephalosporin with the best in vitro activity, comparable to that of the injectable cephalosporins and levofloxacin. Higher MIC₉₀s were found for the macrolides (4 - 16 mg/L) and cefaclor (4 - 32 mg/L). As was foreseeable, Streptococcus pyogenes (225 strains) was uniformly sensitive to all the beta-lactam antibiotics, but the elevated miC90 values reduced (<75%) susceptibility of this pathogen to macrolides. Beta-lactamase-negative Moraxella catarrhalis (100 strains) had reduced susceptibility only to the macrolides, while the 250 beta-lactamase-producing strains also had reduced susceptibility to cefuroxime. Levofloxacin showed the lowest MIC₅₀/MIC₉₀ values in the producing strains, whereas cefditoren, cefotaxime and ceftriaxone in the non-producers. As regards the enterobacteriaceae, cefditoren and levofloxacin had the lowest MIC₉₀s against Klebsiella pneumoniae. Cefditoren and the third-generation injectable cephalosporins had the lowest MIC₉₀s against Escherichia coli (100% susceptibility) while levofloxacin was less active (86% susceptibility).

In conclusion, cefditoren's wide spectrum and high intrinsic activity, as well as its capacity to overcome most of the resistance that has become consolidated in some classes of antibiotics widely used as empiric therapy for CARTI, allows us to suggest that cefditoren might be included in the european guidelines as one of the first-choice antibiotics in the treatment of CARTI.     

In vitro effect of subminimal inhibitory concentrations of antibiotics on the biofilm formation ability of Acinetobacter baumannii clinical isolates

The ability of A cinetobacter baumannii strains to form biofilm is one of the most important virulence factor which enables bacterial survival in a harsh environment and decreases antibiotic concentration as well. Subminimal inhibitory concentrations (subMICs) of antibiotics may change bacterial ultrastructure or have an influence on some different molecular mechanisms resulting in morphological or physiological changes in bacteria itself. The aim of this study was to determine effects of 1/2, 1/4, 1/8 and 1/16 minimal inhibitory concentrationsof imipenem, ampicillin-sulbactam, azithromycin, rifampicin and colistin on biofilm formation ability of 22 biofilm non-producing and 46 biofilm producing A. baumannii strains (30 weak producing strains and 16 moderate producing strains). Results of this study indicate that 1/2–1/16 MICs of imipenem, azithromycin, and rifampicin can reduce bacterial biofilm formation ability in moderate producing strains (p < 0.05), whereas 1/16 MIC of imipenem and 1/4–1/8 MICs of rifampicin reduce the biofilm formation in weak producing strains (p < 0.05). Statisticaly significant effect was detected among biofilm non-producing strains after their exposure to 1/16 MIC of azithromycin (p = 0.039). SubMICs of ampicillin-sulbactam and colistin did not have any significant effect on biofilm formation among tested A. baumannii strains.     

肿瘤患者呼吸道感染嗜血杆菌的临床分布与耐药性分析

  目的   分析肿瘤患者呼吸道感染嗜血杆菌的临床分布与耐药状况，为临床规范应用抗生素提供依据。   方法   收集2010年2月至2010年11月天津医科大学附属肿瘤医院住院的肿瘤患者早晨痰液样本，采用含有Ⅹ、Ⅴ因子的巧克力琼脂平板分离培养嗜血杆菌，应用Vitek2-Compact全自动细菌鉴定分析仪鉴定菌种，药敏试验采用微量肉汤稀释法进行。采用头孢硝噻吩纸片法检测β-内酰胺酶。   结果   从7 333份呼吸道标本中检出316株嗜血杆菌，其中流感嗜血杆菌95株，副流感嗜血杆菌221株。流感嗜血杆菌对头孢噻肟、左氧氟沙星、美罗培南均敏感，对复方新诺明、氨苄西林的耐药率分别为26.3%、15.8%。对头孢类及β-内酰胺/β-内酰胺酶抑制剂、大环内酯类、氯霉素类抗生素较敏感。副流感嗜血杆菌与流感嗜血杆菌的药敏谱相似。   结论   大多数抗菌药物对肿瘤患者呼吸道感染的嗜血杆菌仍保持良好的抗菌活性，临床应根据药敏结果规范使用抗菌药物。      

Annual Author and Subject Indexes Volume 18-2006

Abstract

Resistant clones/phenotypes are putting into question the activity of commonly used β-lactams, thus prompting the need for alternative options. A 500 mg levofloxacin vs. azithromycin once daily pharmacodynamic simulation was performed against 10⁸ cfu/ml of four Streptococcus pneumoniae strains (exhibiting higher amoxicillin than penicillin MIC) and four Haemophilus influenzae strains: β-lactamase producing, BLNAR (β-lactamase-negative ampicillin-resistant) and BLPACR (β- lactamase-positive amoxicillin/clavulanate-resistant). High levofloxacin AUC/MIC values for H. influenzae, and values of 50-100 for S. pneumoniae produced a >5 log₁₀ reduction at 24h for all strains. Azithromycin AUC/MIC values of ?10 were needed to obtain a 2-3 log₁₀ reduction of S. pneumoniae initial inocula, but lower AUC/MIC values (of ?6) obtained ≥3 log₁₀ reduction against all strains of H. influenzae. While in vitro simulated serum concentrations of levofloxacin were bactericidal at the end of the dosing interval against all S. pneumoniae strains and azithromycin against the susceptible ones, both antimicrobials achieved this endpoint against the BLNAR and BLPACR strains.     

Natural Antibiotic Susceptibility of Ewingella americana Strains

Abstract

The natural susceptibility of 20 Ewingella americana strains to 72 antibiotics was examined. MIC values were determined using a microdilution procedure in cation-adjusted Mueller-Hinton broth. Evaluation of natural antibiotic susceptibility was performed applying the German standard (where applicable). β-Lactamases were examined with a conventional nitrocefin colony testing procedure, activity and induction assays, and SDS-PAGE. Ewingella strains were naturally resistant or of intermediate susceptibility to cefaclor, loracarbef, cefazoline, cefuroxime, cefoxitin, benzylpenicillin, oxacillin, fosfomycin, erythromycin, roxithromycin, clarithromycin, lincosamides, dalfopristin-quinupristin, ketolides, linezolid, glycopeptides, fusidic acid and rifampicin. Uniform natural sensitivity was found with acylureidopenicillins except for azlocillin, ticarcillin, several cephalosporins, carbapenems, aztreonam, tetracyclines, aminoglycosides, quinolones, azithromycin, folate-pathway inhibitors and chloramphenicol. Strains of E. americana were naturally sensitive or of intermediate susceptibility to aminopenicillins (with and without β-lactamase inhibitors), azlocillin and nitrofurantoin. All ewingellae yielded β-lactamases; testing of representative strains revealed that these enzymes belong to Ambler class C. Inducibility of β-lactamase was shown for E. americana ATCC 33852^T, CCUG 35675 and CCUG 42782.

The present study describes a database concerning the natural susceptibility of E. americana strains to a range of antibiotics, which can be applied to validate forthcoming antibiotic susceptibility tests of these bacteria. It enlarges the number of Enterobacteriaceae expressing naturally-occurring AmpC β-lactamases.     

Emerging Antimicrobial Resistances Among Proteus mirabilis in Europe: Report from the MYSTIC Program (1997-2001)

Abstract

Resistance patterns that are currently problematic in Europe can vary greatly within the same species over time, among various patient populations and among geographic regions on the same continent. The results from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program, which monitors carbapenem resistance rates in institutions using meropenem, were used to determine resistance differences among Proteus mirabilis. MIC results from 688 P. mirabilis strains were classified into 4 patient care groups: ICU (n=426), neutropenia patients (NP; n=145), general wards (n=97) and cystic fibrosis patients (CF; n=20). A total of 40 centers from 12 European countries have participated since 1997, divided into 3 geographic regions (East, North, South). All testing was performed by NCCLS reference methods and interpretive criteria, including screening of extended-spectrum β-lactamase (ESBL) phenotypes. Over the monitored interval the resistance rates varied for each agent without a clear trend toward a greater rate. Rank order of susceptibility was: meropenem (99%) > piperacillin/tazobactam (TAZ; 96%) > cefepime (95%) > ceftazidime (CAZ; 94%) > imipenem (IPM; 92%). Ciprofloxacin (CIP) was the least active agent tested (MIC₉₀, 4 μg/ml; 86% susceptible). Unexpectedly, 3.6% of P. mirabilis were imipenem-resistant (MIC, >16 μg/ml). Greater rates of resistance were found for strains from NP and CF patients, and from eastern or southern European sites, usually associated with epidemic clusters. Generally susceptible species such as P. mirabilis have recently emerged as therapeutic problems in European medical centers following mutations that compromise CIP, CAZ and aminoglycoside use. Imipenem also showed decreased susceptibility of greater than 7% compared to less than 1% for meropenem. Continued surveillance by the MYSTIC Program appears to be a prudent practice to focus effective empiric treatment regimens.     

Antimicrobial Spectrum and Potency of Dalbavancin Tested Against Clinical Isolates from Europe and North America (2003): Initial Results from an International Surveillance Protocol

Abstract

Dalbavancin is a bactericidal dimethylaminopropyl amide glycopeptide derivative possessing an extended serum elimination half-life in humans that allows onceweekly dosing for the therapy of Gram-positive infections. Strains from this baseline surveillance protocol in North America (NA; USA and Canada) and Europe (EU, 14 countries) were sampled in 2003. A total of 7,765 Gram-positive isolates (3,695 from NA and 4,070 from EU) were tested by reference broth microdilution methods against dalbavancin and 10 comparator agents. Species were analyzed separately by resistance phenotypes such as methicillin- (oxacillin-) resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and penicillin- resistant Streptococcus pneumoniae. Dalbavancin and other glycopeptides were very active against staphylococci (n=4648) with dalbavancin being 16- to 32- fold more potent than vancomycin (MIC₉₀, 0.06 versus 2 mg/L). MRSA rates were greater (31.6%) in NA than in EU (26.1%). Quinupristin/dalfopristin resistance (MIC, ≥ 2 mg/L; 0.1 - 0.5%) was documented more often in EU compared to NA. Dalbavancin (MIC₅₀, 0.03 - 0.06 mg/L) was active against enterococci, except VanA resistance phenotypes. VRE rates were lower in EU (8.3%) then in NA (35.9%) from this resistance-enhanced enterococcal collection. Streptococci (dalbavancin MIC₉₀, 0.016 - 0.03 mg/L) were generally most susceptible to glycopeptides (100.0%), quinupristin/dalfopristin (98.6 - 100.0%) and linezolid (100.0%); but dalbavancin was 16-fold more active than comparators. All vancomycin-susceptible enterococci and > 90% of vanB VRE had dalbavancin MIC values at ≤ 1 mg/L, but vanA VRE strains had dalbavancin MIC results ranging from 0.06 to > 8 mg/L (median MIC, ≥ 8 mg/L). Dalbavancin MIC values were not adversely influenced by geographic region or resistance phenotype (except vanA VRE). Infrequently isolated Gram-positive organisms such as Bacillus spp. (MIC₉₀, 0.12 mg/L), Corynebacterium spp. (MIC₉₀, 0.12 mg/L), Listeria monocytogenes (MIC₉₀, 0.25 mg/L) and Micrococcus spp. (MIC₉₀, 0.03 mg/L) were very susceptible to dalbavancin. In conclusion, these 2003 baseline resistance surveillance findings confirm the potent dalbavancin activity compared to several comparator agents against important Gram-positive pathogens. This high volume international survey indicates potential therapeutic roles for dalbavancin against many troublesome resistant Gram-positive phenotypes.     

The Pharmacokinetics and Pharmacodynamics of Meropenem in the Cerebrospinal Fluid of Neurosurgical Patients

Abstract

This study examined the pharmacokinetics and pharmacodynamics of meropenem in cerebrospinal fluid (CSF). Meropenem (0.5 g every 8 h) was administered by 0.5-h infusion to six neurosurgical patients. Lumbar CSF and venous blood samples were obtained at 0.5-16 h after the start of the first infusion. Drug concentrations in the CSF and plasma were analyzed pharmacokinetically and used for a Monte Carlo simulation with the minimum inhibitory concentration (MIC) data of clinical isolates in Japan. Meropenem penetrated into the CSF with the area under the drug concentration-time curve ratio of 0.10 ± 0.03 (mean ± SD) and the repeated infusions caused the drug concentration in the CSF to accumulate slightly. Against Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, and Escherichia coli isolates, 0.5 g q8h achieved a >90% probability of pharmacodynamic target (50% of the time above MIC) attainment, and 1 g q8h was needed for a >90% probability of target (100% of the time above MIC) attainment. However, against Pseudomonas aeruginosa, 2 g q8h achieved a lower probability of target attainment. These results should help us to better elucidate the pharmacokinetics of meropenem in the cerebrospinal space while also helping us to choose the appropriate drug dosages for the management of bacterial meningitis.     

In- Vitro Susceptibility of Clinical Isolates of Pseudomonas aeruginosa to β-Lactam and Aminoglycoside Antibiotics

Summary

The in-vitro susceptibilities of 198 isolates of Pseudomonas aeruginosa from clinical human specimens were determined by an agar dilution technique against (β-lactams and aminoglycosides. These isolates were susceptible to imipenem, aztreonam and ceftazidime with the minimum inhibitory concentration (MIC) for 90% of the strains tested being 8, 16 and 8 μg/ml, respectively. Aminoglycosides, except amikacin, had low activity (MIC90 > 128 μg/ml).     

Inhibitory and Bactericidal Activity of Rokitamycin against Helicobacter pylori and Morphological Alterations

Abstract

Rokitamycin is a macrolide antibiotic, recently entered into clinical use. Its in vitro activity and kill kinetics against Helicobater pylori have been evaluated at 1 x the minimum inhibitory concentration (MIC), 2×MIC and 4×MIC at 2, 4, 8, 24 hours and compared with those of clarithromycin, erythromycin and amoxicillin. Morphological changes in H. pylori induced by rokitamycin incubation at these MICs and times were also investigated by scanning electron microscopy. All the antibiotics tested had good inhibitory activity against H. pylori, a slow growing microorganism. The order of MIC activity was clarithromycin > amoxicillin > rokitamycin > erythromycin. Rokitamycin killed more rapidly than the other antibiotics, in fact H. pylori strains were totally killed at 8 h (2×MIC) and 4 h ( 4×MIC) and after only 2h incubation all concentrations greatly decreased the CFU/ml. These effects were also confirmed by the rapid appearance of surface and morphological alterations (focal blebs, constrictions, rounded forms) in the normal structure of H. pylori observed by scanning electron microscopy. Clinical studies should be conducted to investigate the in vivo activity of rokitamycin, as an agent to be used in the combination therapies against H. pylori.     

Susceptibility of Respiratory and Urinary Pathogens to Ceftibuten and Other Comparative Drugs: Results of an Italian Multicenter Survey

Summary

A survey aimed at assessing the ability of ceftibuten, a new oral third-generation cephalosporin, to eradicate in Vitro selected bacterial pathogens was conducted in 1991 in 17 microbiology laboratories evenly distributed in Italy. Over 8700 organisms collected from in- and outpatients affected mainly by respiratory and urinary tract infections were analyzed. This collection of bacteria did not include staphylococci, enterococci, Pseudomonta and other oxidative species naturally refractory to the action of most antibiotics employed.

Susceptibility to ceftibuten, cefaclor, cefuroxime, amoxicillin, amoxicillin-clavulanate, cotrimoxazole and erythromycin was assessed using a standardized agar-diffusion method. Production of β-lactamases was confirmed by the nitrocefin test. Among the microorganisms studied E. coli (32.1%) prevailed, followed by P. mirabilis (17.1%), K. pneumoniae (10.9%), 5. pyogenes (6.6%), E. cloacae (5.1%), Serratia spp. (4.5%), Enterobacter spp. (4.2%), H. influenzae (3.6%), S. pneumoniae (2.2%) and Af. catarrhalis (2%). Within this group of pathogens amoxicillin resistance, often mediated by synthesis of P-lactamases, was widely diffused (46.2%). The overall inhibitory activity of the drugs tested decreased as follows: ceftibuten (90.4%), cefuroxime (80.4%), amoxicillin-clavulanate (77.4%), cotrimoxazole (75.3%), cefaclor (72.6%), amoxicillin (53.8%) and erythromycin (32.8%). When the efficacy of the antibiotics was assessed against the collection of respiratory isolates producing β-lactamases only ceftibuten maintained the same overall potency manifested against the general population while the comparative agents were far less effective. The results of this national survey indicate that, given the low incidence of resistance among the most prevalent causative agents of respiratory and urinary tract infections, ceftibuten can be safely used at present in the empiric therapy of these conditions especially when they occur in community settings.     

Cefaclor in the Treatment of Infective Exacerbations of Chronic Bronchitis in Cigarette Smokers

Summary

There is a direct correlation between number of cigarettes smoked and the incidence of lower respiratory tract infection in humans. In studies with smokers suffering from exacerbations of chronic bronchitis, the most common bacterial pathogens found were Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus and Branhamella catarrhalis. Antibiotics should be effective against such possible pathogens. Cefaclor has demonstrated in vitro activity against all these pathogens. We designed the present study to evaluate the efficacy and safety of cefaclor in the treatment of acute exacerbations of chronic bronchitis in cigarette smokers. A total of 106 patients were enrolled in the study. H. influenzae was the most common bacterial species isolated in the sputum (in 23.6% of the total sample), followed by S. pneumoniae (18.9%), S. aureus (17.0%), K. pneumoniae (7.5%) and B. catarrhalis (5.7%), while mixed forms were present in 22.6% of cases and other pathogens in 4.7%. Cefaclor (500 mg) was given orally every 8h for 7 to 16 days (mean 10.73 ±2.11). Analysis of clinical response data indicates that 75.5% of patients were cured and 17.0% improved. This finding is important because it demonstrates that cefaclor’s spectrum of activity encompasses all the most likely pathogens encountered in smokers. Because of its excellent response rate, cefaclor is of particular value in the treatment of lower respiratory tract infections in cigarette smokers.     

Comparative Evaluation of Orally Active Antibiotics against Community-Acquired Pathogens: a Multi-Center Study in Five Mediterranean Countries

Abstract

In 5 Mediterranean countries 7902 pathogens, all isolated in 1992 and 1993 from community-acquired infections, were studied for susceptibility to the following orally active antibiotics: penicillin G, ampicillin, ampi-cillin + sulbactam, amoxycillin + clavulanic acid (both 2:1 ratio), cefalexin, cefaclor, cefuroxime, cefetamet, doxycycline and erythromycin. Ten centers in Italy, 4 centers in Greece, 3 centers in Spain, and 1 center in Lebanon and Saudi Arabia contributed to this study; all centers used preformed standardized microtiter panels (Sceptor^®, BBL, Heidelberg, FRG). The most frequently isolated pathogens were Escherichia coli (n=1267), Proteus mirabilis (n = 843), Klebsiella pneumoniae (n=771), enteric Salmonella spp. (n=629), Enterobacter cloacae (n = 486), Citrobacter freundii (n = 383), Streptococcus agalactiae (n=346), Haemophilus influenzae (n=298), Streptococcus pyogenes (n=294), Streptococcus pneumoniae (n=246), Klebsiella oxytoca (n=243), and Shigella spp. (n=185). Statistical analysis was performed for each of the above countries and for all pooled data available. The penicillin antibiotics were the most active compounds against the gram-positive cocci, exceeding the MIC₉₀ values 2- to 8-fold over all cephalosporins. Regarding the gram-negatives (above all Klebsiella spp.) cefetamet was by far the most active compound (MIC₉₀ = 1 mg/1). Regarding the percentage of resistant isolates, there were no striking discrepancies between the centers and countries involved in this study. There was, however, complete cross-resistance in penicillin-resistant S. pneu moniae isolates (MIC₉₀ = 2 mg/l). By far the majority of the penicillin-resistant pneumococci showed additional resistance to doxycycline and erythromycin. Regarding all 11 compounds included in this study cefetamet was the only agent with well balanced activity against both gram- positive and gram-negative pathogens.     

Assessment of the Susceptibility of Streptococcus pneumoniae to Cefaclor and Loracarbef in 13 Countries

Abstract

Between July 1998 and July 1999, 2,644 clinical isolates of Streptococcus pneumoniae were collected from 27 study centers in 13 countries and their susceptibilities to penicillin, cefaclor and loracarbef were determined by E-test” (AB BIODISK, Solna, Sweden). Overall, 96.3% of isolates were penicillin-susceptible (79.8%) or -intermediate (16.6%) (MIC, <1 μg/ml). Rates of penicillin-resistant S. pneumoniae isolation varied widely and were highest in the study centers tested in New Zealand (10.9%), Canada (10.0%), Mexico (9.1%) and the United States (5.1%). Low rates of penicillin-resistance were found in the study centers tested in Russia (0%), Turkey (0%), Brazil (0.5%), Germany (0.6%), Philippines (1.6%), Italy (2.1%), United Kingdom (2.3%), Australia (3.0%) and Poland (3.1%). Using recently published NCCLS interpretative breakpoints (M100-S10, 2000), 87.2% (median) of all isolates tested were cefaclor-susceptible and 87.8% (median) of all isolates tested were loracarbef-susceptible. Of the penicillin-susceptible S. pneumoniae isolates, 99.5% were susceptible to both cefaclor and loracarbef. Susceptibility to cefaclor and loracarbef was also retained by 30.8% and 32.9% of penicillin-intermediate isolates, respectively. These findings are in contrast to recent publications reporting lower cefaclor and loracarbef activities using non-validated interpretative criteria. In conclusion, rates of penicillin resistance among recent clinical isolates of pneumococci remain low in many centers worldwide. Cefaclor and loracarbef demonstrated excellent in vitro activity against recent clinical isolates of penicillin-susceptible and many isolates of penicillin-intermediate S. pneumoniae.     

Antibacterial Resistance in Streptococcus pneumoniaeand Haemophilus influenzae from Italy and Spain: Data from the PROTEKT Surveillance Study, 1999–2000

Abstract

Antibacterial resistance was evaluated among Streptococcus pneumoniae (n=252) and Haemophilus influenzae (n=202) from two centres in Spain (Barcelona and Madrid) and two centres in Italy (Genoa and Catania) collected during 1999–2000 as part of the ongoing PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) international surveillance program. Pneumococcal nonsusceptibility to penicillin G was found to be considerably higher in Spain (53.4%) than in Italy (15.1%), whereas erythromycin A resistance was higher in Italy (42.9%) than in Spain (28.6%). Among macrolide-resistant isolates investigated for resistance genes, the prevalence of mefA was higher among isolates from Italy (20/51, 39.2%) than among Spanish isolates (2/38, 5.3%). All other macrolide-resistant isolates possessed ermB. Telithromycin possessed good anti-pneumococcal activity against isolates from both countries (MIC₉₀ 0.03 mg/L [Spain]; 0.25 mg/L [Italy]), irrespective of resistance to other antibacterials. β-lactamase production among H. influenzae was low: Spain, 10.9%; Italy, 1.8%. With the exception of ampicillin and co-trimoxazole, all H. influenzae isolates were highly susceptible to the antibacterials tested, and all were inhibited by telithromycin at a concentration of ≤2 mg/L. The findings of PROTEKT 1999–2000 highlight the importance of local resistance patterns in guiding the choice of empirical antibacterials for community-acquired respiratory tract infections.     

Antimicrobial Resistance and Prevalence of Extended Spectrum β-Lactamase Among Clinical Isolates of Gram-Negative Bacteria in Riyadh

Abstract

The activity of ciprofloxacin, imipenem and 12 other commonly used antibiotics was evaluated against 106 documented clinical isolates from a medical Intensive Care Unit (ICU). The resistance rates to ceftriaxone, cefotaxime, aztreonam and ceftazidime were 42, 25, 24 and 21%, respectively. Apart from Pseudomonas aeruginosa, all isolates were sensitive to ciprofloxacin and imipenem. Complete cross resistance among tested β-lactam groups was uniformly evident in Enterobacter cloacae, Citrobacter freundii and P. aeruginosa. On the other hand, penicillins and second generation cephalosporins showed cross resistance among Escherichia coli and Klebseilla pneumoniae isolates. Induction experiments indicate that 70 and 62% of P. aeruginosa and E. cloacae or C. freundii produce class I cephalosporinase, respectively.

Among all tested isolates, plasmid mediated extended spectrum β-lactamase (ESBL) was detected in one isolate of K. pneumoniae. The plasmid mediated β-lactamase is transferable and inhibited by β-lactamase inhibitors. The transconjugates not only expressed resistance to extended spectrum β-lactams and aztreon-am but also toward tested aminoglycoside antibiotics, with the exception of gentamicin. The obtained transconjugates conferred high level resistance to cef-tazidime and aztreonam but considerably low resistance to ceftriaxone and cefotaxime. The isoelectric point for the extended-spectrum β-lactamase is 8.2.     

In Vitro Activity of Cefpirome (HR 810) against Enterococci and Staphylococci

Summary

The inhibitory activity of cefpirome (HR 810), a new cephalosporin derivative for parenteral use, was tested by agar dilution methods against Enterococcus faecatis (100 strains), Staphylococcus aureus (40 strains) and coagulase-negative staphylococcal species (60 strains) in comparison with other beta-lac ta m antibiotics.

For E. faecalls, the cefpirome minimum inhibitory concentration (MIC) range was 2-128 μg/ml, with an MIC,, of 8 μg/ml, and an MIC₉₀, of 64 μg/ml. The optimal bactericidal activity against strains with MICs of ≤ 8 μg/ml occurred at 2-4 times the MIC, and the reduction in the initial inoculum was 99.9-99.7% after 24 h incubation at these concentrations.

Mec gene-negative staphylococci (both S. aureus and coagulase- negative species) had cefpirome MICs of 0.25-2 μg/ml (MIC₅₀ 0.5 μg/ml, MIC₉₀ 1 μg/ml). Mec gene-positive strains had MICs of 0.5-128 μg/ml (MIC₅₀ 2 μg/ml, MIC₉₀ 32 μg/ml). Strains with borderline resistance to oxacillin which did not harbor the mec gene and which were susceptible to cefpirome maintained their susceptibility even when high-density inocula were used and after several passages in media containing the antibiotic.

These studies present some potential advantages of cefpirome over other cephalosporins in the inhibitory activity against Gram-positive cocci.     

Bacterial Isolates from Severe Infections and Their Antibiotic Susceptibility Patterns in Italy: a Nationwide Study in the Hospital Setting

Abstract

The most frequent agents of severe bacterial infections and their antibiotic susceptibility patterns were determined in patients admitted to 45 Italian hospitals over the years 2002-2003. The most common diagnoses were: sepsis (33.8%), pneumonia (9.4%), intravascular catheter-associated infections (9.3%) and ventilator- associated pneumonia (8.1%). Overall, 5115 bacterial isolates were identified from 4228 patients. Three bacterial species, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, accounted for more than 50% of the isolates. Other prevalent bacterial isolates were Staphylococcus epidermidis and Enterococcus faecalis, while Acinetobacter baumanii ranked third among all Intensive Care Unit (ICU) isolates. 7% of S. aureus had intermediate resistance to vancomycin. Although E. faecalis displayed no vancomycin resistance, 34% of vancomycin- resistant isolates were found among Enterococcus faecium, one of the highest rates found to date, emphasizing the difference between these two enterococcal species. All the Gram-positive pathogens were susceptible to linezolid, with the exception of approximately 2% of the enterococcal isolates that were intermediate with a minimum inhibitory concentration (MIC)=4 μg/ml. Almost 10% of Escherichia coli, 14% of Klebsiella pneumoniae, 22% of Serratia marcescens and 50% of Enterobacter cloacae were non-susceptible to cefotaxime. Amikacin was the most active antibiotic against P. aeruginosa that showed lack of susceptibility to ceftazidime, gentamicin, piperacillin and ciprofloxacin ranging from 20 to 35%. Finally, Acinetobacter baumanii showed a high level of resistance to all the antibiotics tested including imipenem (58%). The results obtained in this study, the first of its kind in Italy, offer indications for guiding empirical therapy and implementing specific interventions to fight antibiotic-resistant bacterial infections and their transmission in the hospital setting in Italy.