Showing papers on "Penicillin published in 2004"

Decrease of Invasive Pneumococcal Infections in Children Among 8 Children’s Hospitals in the United States After the Introduction of the 7-Valent Pneumococcal Conjugate Vaccine

Abstract: Objective. To monitor clinical and microbiologic features including antimicrobial susceptibility and serogroup distribution of invasive infections caused by Streptococcus pneumoniae among children before and after the introduction of routine administration of the 7-valent pneumococcal conjugate vaccine (PCV7). Design. A 9-year (January 1, 1994 through December 31, 2002) prospective surveillance study of all invasive pneumococcal infections in children. Patients. Infants and children cared for at 8 children’s hospitals in the United States with culture-proven invasive infections caused by S pneumoniae. Results. When compared with the mean of the years 1994 to 2000, the annual number of invasive pneumococcal infections for children ≤24 months of age declined 58% in 2001 and 66% in 2002. If only the serogroups in the PCV7 are considered, the number of cases in children ≤24 months old declined 63% and 77% in 2001 and 2002, respectively. The greatest decrease was observed for serogroup-14 isolates. The number of isolates in nonvaccine serogroups increased 28% in 2001 and 66% in 2002 for children ≤24 months old. Nonvaccine serogroup-15 and -33 isolates had the greatest increase in number. The proportion of all isolates nonsusceptible to penicillin increased yearly from 1994 to 2000, reached a plateau in 2001 at 45%, and declined to 33% in 2002. Decrease in nonsusceptibility to penicillin occurred entirely in the isolates with penicillin minimum inhibitory concentration ≥2 μg/mL. Nonsusceptibility to penicillin increased slightly among nonvaccine-serotype isolates. Most infections after at least 2 doses of PCV7 were caused by nonvaccine-serotype isolates. Conclusions. Since the introduction of the PCV7, the number of invasive pneumococcal infections caused by vaccine-serogroup isolates among 8 US children’s hospitals has decreased >75% among children ≤24 months old. In addition, penicillin resistance decreased in 2002 for the first time since our surveillance began in 1993–1994. However, we have noted that replacement may be developing with serogroups 15 and 33. Furthermore, penicillin resistance seems to be increasing among nonvaccine serogroups. Surveillance must be continued to detect the emergence of changes in the distribution of serotypes as well as antibiotic susceptibility.

Augmentin ® (amoxicillin/clavulanate) in the treatment of community-acquired respiratory tract infection: a review of the continuing development of an innovative antimicrobial agent

Abstract: Amoxicillin/clavulanate (Augmentin ® ) is a broad-spectrum antibacterial that has been available for clinical use in a wide range of indications for over 20 years and is now used primarily in the treatment of community- acquired respiratory tract infections. Amoxicillin/clavulanate was developed to provide a potent broad spec- trum of antibacterial activity, coverage of β-lactamase-producing pathogens and a favourable pharmaco- kinetic/pharmacodynamic (PK/PD) profile. These factors have contributed to the high bacteriological and clinical efficacy of amoxicillin/clavulanate in respiratory tract infection over more than 20 years. This is against a background of increasing prevalence of antimicrobial resistance, notably the continued spread of β-lactamase-mediated resistance in Haemophilus influenzae and Moraxella catarrhalis, and penicillin, macrolide and quinolone resistance in Streptococcus pneumoniae. The low propensity of amoxicillin/ clavulanate to select resistance mutations as well as a favourable PK/PD profile predictive of high bacterio- logical efficacy may account for the longevity of this combination in clinical use. However, in certain defined geographical areas, the emergence of S. pneumoniae strains with elevated penicillin MICs has been observed. In order to meet the need to treat drug-resistant S. pneumoniae, two new high-dose amoxicillin/ clavulanate formulations have been developed. A pharmacokinetically enhanced tablet dosage form of amoxicillin/clavulanate 2000/125 mg twice daily (available as Augmentin XR ® in the USA), has been devel- oped for use in adult respiratory tract infection due to drug-resistant pathogens, such as S. pneumoniae with reduced susceptibility to penicillin, as well as β-lactamase-producing H. influenzae and M. catarrhalis. Amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses (Augmentin ES-600 ® ) is for paediatric use in persistent or recurrent acute otitis media where there are risk factors for the involvement of β-lactamase- producing strains or S. pneumoniae with reduced penicillin susceptibility. In addition to high efficacy, amoxicillin/clavulanate has a well known safety and tolerance profile based on its use in over 819 million patient courses worldwide. Reassuringly, the safety profiles of the two new high-dose formulations are not significantly different from those of conventional formulations. Amoxicillin/clavulanate is included in guide- lines and recommendations for the treatment of bacterial sinusitis, acute otitis media, community-acquired pneumonia and acute exacerbations of chronic bronchitis. Amoxicillin/clavulanate continues to be an important agent in the treatment of community-acquired respiratory tract infections, both now and in the future.

An Open, Randomized, Controlled Trial of Penicillin, Doxycycline, and Cefotaxime for Patients with Severe Leptospirosis

Abstract: Background Leptospirosis is an important cause of fever in the rural tropics. Since 1996, there has been a marked increase in the incidence of leptospirosis in northeastern Thailand. Although leptospirosis generally is susceptible to antibiotics, there is no consensus regarding the optimal treatment for severe leptospirosis. Methods An open-label, randomized comparison of parenteral cefotaxime, penicillin G sodium (hereafter known as "penicillin G"), and doxycycline for the treatment of suspected severe leptospirosis was conducted. The study involved 540 patients admitted to 4 hospitals in northeastern Thailand. Results A total of 264 patients (48.9%) had leptospirosis confirmed by serologic testing or culture. The overall mortality rate was 5%. There were no significant differences between the antibiotics with regard to associated mortality, defervescence, or time to resolution of abnormal findings of laboratory tests either among all study participants or among the subgroup of patients with confirmed leptospirosis. A total of 132 patients had rickettsial infection diagnosed, and, for these patients, treatment with doxycycline was superior to treatment with penicillin G. Conclusions Doxycycline or cefotaxime is a satisfactory alternative to penicillin G for the treatment of severe leptospirosis.

Meta-analysis of cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis in children.

Abstract: Objective. To conduct a meta-analysis of randomized, controlled trials of cephalosporin versus penicillin treatment of group A β-hemolytic streptococcal (GABHS) tonsillopharyngitis in children. Methodology. Medline, Embase, reference lists, and abstract searches were conducted to identify randomized, controlled trials of cephalosporin versus penicillin treatment of GABHS tonsillopharyngitis in children. Trials were included if they met the following criteria: patients Results. Thirty-five trials involving 7125 patients were included in the meta-analysis. The overall summary odds ratio (OR) for the bacteriologic cure rate significantly favored cephalosporins compared with penicillin (OR: 3.02; 95% confidence interval [CI]: 2.49–3.67, with the individual cephalosporins [cephalexin, cefadroxil, cefuroxime, cefpodoxime, cefprozil, cefixime, ceftibuten, and cefdinir] showing superior bacteriologic cure rates). The overall summary OR for clinical cure rate was 2.33 (95% CI: 1.84–2.97), significantly favoring the same individual cephalosporins. There was a trend for diminishing bacterial cure with penicillin over time, comparing the trials published in the 1970s, 1980s, and 1990s. Sensitivity analyses for bacterial cure significantly favored cephalosporin treatment over penicillin treatment when trials were grouped as double-blind (OR: 2.31; 95% CI: 1.39–3.85), high-quality (OR: 2.50; 95% CI: 1.85–3.36) trials with well-defined clinical status (OR: 2.12; 95% CI: 1.54–2.90), with detailed compliance monitoring (OR: 2.85; 95% CI: 2.33–3.47), with GABHS serotyping (OR: 3.10; 95% CI: 2.42–3.98), with carriers eliminated (OR: 2.51; 95% CI: 1.55–4.08), and with test of cure 3 to 14 days posttreatment (OR: 3.53; 95% CI: 2.75–4.54). Analysis of comparative bacteriologic cure rates for the 3 generations of cephalosporins did not show a difference. Conclusions. This meta-analysis indicates that the likelihood of bacteriologic and clinical failure of GABHS tonsillopharyngitis is significantly less if an oral cephalosporin is prescribed, compared with oral penicillin.

MICs of Selected Antibiotics for Bacillus anthracis, Bacillus cereus, Bacillus thuringiensis, and Bacillus mycoides from a Range of Clinical and Environmental Sources as Determined by the Etest

Abstract: This paper presents Etest determinations of MICs of selected antimicrobial agents for 76 isolates of Bacillus anthracis chosen for their diverse histories and 67, 12, and 4 cultures, respectively, of its close relatives B. cereus, B. thuringiensis, and B. mycoides derived from a range of clinical and environmental sources. NCCLS breakpoints are now available for B. anthracis and ciprofloxacin, penicillin, and tetracycline; based on these breakpoints, the B. anthracis isolates were all fully susceptible to ciprofloxacin and tetracycline, and all except four cultures, three of which had a known history of penicillin resistance and were thought to originate from the same original parent, were susceptible to penicillin. Based on NCCLS interpretive standards for gram-positive and/or aerobic bacteria, all cultures were susceptible to amoxicillin-clavulanic acid and gentamicin and 99% (one with intermediate sensitivity) of cultures were susceptible to vancomycin. No group trends were apparent among the different categories of B. cereus (isolates from food poisoning incidents and nongastrointestinal infections and food and environmental specimens not associated with illness). Differences between B. anthracis and the other species were as expected for amoxicillin and penicillin, with all B. anthracis cultures, apart from the four referred to above, being susceptible versus high proportions of resistant isolates for the other three species. Four of the B. cereus and one of the B. thuringiensis cultures were resistant to tetracycline and a further six B. cereus and one B. thuringiensis cultures fell into the intermediate category. There was a slightly higher resistance to azithromycin among the B. anthracis strains than for the other species. The proportion of B. anthracis strains fully susceptible to erythromycin was also substantially lower than for the other species, although just a single B. cereus strain was fully resistant. The Etest compared favorably with agar dilution in a subsidiary test set up to test the readings, and it compared with other published studies utilizing a variety of test methods.

Drug-Resistant Pneumococcal Pneumonia: Clinical Relevance and Related Factors

Abstract: A multicenter study of 638 cases of community-acquired pneumonia due to Streptococcus pneumoniae (SP-CAP) was performed to assess current levels of resistance. Of the pneumococcal strains, 35.7% had an minimum inhibitory concentration (MIC) of penicillin of > or =0.12 microg/mL (3 isolates had an MIC of 4 microg/mL), 23.8% had an MIC of erythromycin of 128 microg/mL, and 22.2% were multidrug resistant. Logistic regression determined that chronic pulmonary disease (odds ratio [OR], 1.44], human immunodeficiency virus infection (OR, 1.98), clinically suspected aspiration (OR, 2.12), and previous hospital admission (OR, 1.69) were related to decreased susceptibility to penicillin, and previous admission (OR, 1.89) and an MIC of penicillin of MIC > or =0.12 microg/mL (OR, 15.85) were related to erythromycin resistance (MIC, > or =1 microg/mL). The overall mortality rate was 14.4%. Disseminated intravascular coagulation, empyema, and bacteremia were significantly more frequent among patients with penicillin-susceptible SP-CAP. Among isolates with MICs of penicillin of > or =0.12 microg/mL, serotype 19 was predominant and was associated with a higher mortality rate. In summary, the rate of resistance to beta -lactams and macrolides among S. pneumoniae that cause CAP remains high, but such resistance does not result in increased morbidity.

Daptomycin Is Highly Efficacious against Penicillin-Resistant and Penicillin- and Quinolone-Resistant Pneumococci in Experimental Meningitis

Abstract: The penetration of daptomycin, a new lipopeptide antibiotic, into inflamed meninges ranged between 4.37 and 7.53% (mean, 5.97%). Daptomycin was very efficacious in the treatment of experimental pneumococcal meningitis, producing a decrease of -1.20 +/- 0.32 Deltalog(10) CFU/ml. h in the bacterial titer of Streptococcus pneumoniae against a penicillin-resistant strain and of -0.97 +/- 0.32 Deltalog(10) CFU/ml. h against a penicillin- and quinolone-resistant strain found in cerebrospinal fluid (CSF). For both strains, daptomycin was significantly superior to the standard regimen of a combination of ceftriaxone with vancomycin, sterilizing 9 of 10 CSF samples after 4 h. In vitro, daptomycin produced highly bactericidal activity in concentrations above the MIC.

Levofloxacin-Resistant Invasive Streptococcus pneumoniae in the United States: Evidence for Clonal Spread and the Impact of Conjugate Pneumococcal Vaccine

Abstract: The emergence of fluoroquinolone resistance in sterile-site isolates of Streptococcus pneumoniae is documented in this study characterizing all invasive levofloxacin-resistant (MIC, > or = 8 mg/liter) S. pneumoniae isolates (n = 50) obtained from the Centers for Disease Control and Prevention Active Bacterial Core Surveillance from 1998 to 2002. Resistance among all isolates increased from 0.1% in 1998 to 0.6% in 2001 (P = 0.008) but decreased to 0.4% in 2002, while resistance among vaccine serotypes continued to increase from 0.3% in 1998 to 1.0% in 2002, suggesting that fluoroquinolones continue to exert selective pressure on these vaccine serotypes. Only 22% of resistant isolates were not covered by the conjugate vaccine serogroups. Multilocus sequence typing revealed that 58% of resistant strains were related to five international clones identified by the Pneumococcal Molecular Epidemiology Network, with the Spain(23F)-1 clone being most frequent (16% of all isolates). Thirty-six percent of the isolates were coresistant to penicillin, 44% were coresistant to macrolides, and 28% were multiresistant to penicillin, macrolides, and fluoroquinolones. Fifty percent of the isolates were resistant to any three drug classes. Ninety-four percent of the isolates had multiple mutations in the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes. In 16% of the isolates, there was evidence of an active efflux mechanism. An unusual isolate was found that showed only a single parE mutation and for which the ciprofloxacin MIC was lower (2 mg/liter) than that of levofloxacin (8 mg/liter). Our results suggest that invasive pneumococcal isolates resistant to levofloxacin in the United States show considerable evidence of multiple resistance and of clonal spread.

Regulation of penicillin biosynthesis in filamentous fungi

Abstract: The beta-lactam antibiotic penicillin is one of the mainly used antibiotics for the therapy of infectious diseases. It is produced as end product by some filamentous fungi only, most notably by Aspergillus (Emericella) nidulans and Penicillium chrysogenum. The penicillin biosynthesis is catalysed by three enzymes which are encoded by the following three genes: acvA (pcbAB), ipnA (pcbC) and aatA (penDE). The genes are organised into a gene cluster. Although the production of secondary metabolites as penicillin is not essential for the direct survival of the producing organisms, several studies indicated that the penicillin biosynthesis genes are controlled by a complex regulatory network, e.g. by the ambient pH, carbon source, amino acids, nitrogen etc. A comparison with the regulatory mechanisms (regulatory proteins and DNA elements) involved in the regulation of genes of primary metabolism in lower eukaryotes is thus of great interest. This has already led to the elucidation of new regulatory mechanisms. Positively acting regulators have been identified such as the pH dependent transcriptional regulator PACC, the CCAAT-binding complex AnCF and seem also to be represented by recessive trans-acting mutations of A. nidulans (prgA1, prgB1, npeE1) and R chrysogenum (carried by mutants Npe2 and Npe3). In addition, repressors like AnBH1 and VeA are involved in the regulation. Furthermore, such investigations have contributed to the elucidation of signals leading to the production of penicillin and can be expected to have a major impact on rational strain improvement programs.

Remarkable increase in central Japan in 2001-2002 of Neisseria gonorrhoeae isolates with decreased susceptibility to penicillin, tetracycline, oral cephalosporins, and fluoroquinolones.

Abstract: Four hundred sixty-two clinical isolates of Neisseria gonorrhoeae recovered from 1999 through 2002 in central Japan were examined for MICs of antimicrobial agents. The majority was sensitive to ceftriaxone and spectinomycin, but a remarkable increase in isolates with decreased susceptibility to penicillin, tetracycline, oral cephalosporins, and fluoroquinolones was observed from 2001 through 2002.

Emergence of Streptococcus pneumoniae with Very-High-Level Resistance to Penicillin

Abstract: Penicillin resistance threatens the treatment of pneumococcal infections. We used sentinel hospital surveillance (1978 to 2001) and population-based surveillance (1995 to 2001) in seven states in the Active Bacterial Core surveillance of the Emerging Infections Program Network to document the emergence in the United States of invasive pneumococcal isolates with very-high-level penicillin resistance (MIC ≥ 8 μg/ml). Very-high-level penicillin resistance was first detected in 1995 in multiple pneumococcal serotypes in three regions of the United States. The prevalence increased from 0.56% (14 of 2,507) of isolates in 1995 to 0.87% in 2001 (P = 0.03), with peaks in 1996 and 2000 associated with epidemics in Georgia and Maryland. For a majority of the strains the MICs of amoxicillin (91%), cefuroxime (100%), and cefotaxime (68%), were ≥8 μg/ml and all were resistant to at least one other drug class. Pneumonia (50%) and bacteremia (36%) were the most common clinical presentations. Factors associated with very highly resistant infections included residence in Tennessee, age of <5 or ≥65 years, and resistance to at least three drug classes. Hospitalization and case fatality rates were not higher than those of other pneumococcal infection patients; length of hospital stay was longer, controlling for age. Among the strains from 2000 and 2001, 39% were related to Tennessee23F-4 and 35% were related to England14-9. After the introduction of the pneumococcal conjugate vaccine, the incidence of highly penicillin resistant infections decreased by 50% among children <5 years of age. The emergence, clonality, and association of very-high-level penicillin resistance with multiple drug resistance requires further monitoring and highlights the need for novel agents active against the pneumococcus.

Capsular Expression in Streptococcus pneumoniae Negatively Affects Spontaneous and Antibiotic-Induced Lysis and Contributes to Antibiotic Tolerance

Abstract: Penicillin and vancomycin induce a lytic response in Streptococcus pneumoniae that requires the N-acetylmuramyl-l-alanine amidase LytA. We show that clinical isolates of pneumococci of capsular serotypes 1, 4, 6B, and 23F were generally less lytic to penicillin than pneumococci of serotypes 14 and 3. In addition, most 9V isolates were less lytic to vancomycin, compared with isolates of other serotypes. Parent-mutant pairs expressing and not expressing capsular serotypes 2, 4, and 9V were compared for antibiotic-induced lysis. The nonencapsulated variants were considerably more lytic after beta-lactam and/or vancomycin treatment, and antibiotic tolerance was seen only in the context of capsule expression. Conversion from a nonlytic to a lytic phenotype, after loss of capsule expression, required an intact lytA autolysin gene. Exogenous addition of purified LytA gave a lower lytic response in capsulated strains, compared with that in nonencapsulated mutants. Spontaneous autolysis in stationary phase also was negatively affected by capsule expression in an autolysin-dependent manner. Long-term starvation in the stationary phase of the vancomycin- and penicillin-tolerant isolate I95 yielded nonencapsulated mutants that had lost antibiotic tolerance and were lytic to penicillin and vancomycin. The 9V capsular locus of I95 and one of these stationary phase-selected mutants were completely sequenced. The only difference found was a 1-bp frameshift deletion in the cps9vE gene of the lytic mutant, encoding a uridine diphosphate-glucosyl-1-phosphate transferase. Two additional independently isolated lytic mutants of I95 from the stationary phase also contained mutations in the same region of cps9vE, which identified it as a mutational hot spot. This report demonstrates that capsular polysaccharides negatively influence the lytic process and contribute to antibiotic tolerance in clinical isolates of pneumococci.

β-Lactamase Gene Expression in a Penicillin-Resistant Bacillus anthracis Strain

Abstract: Expression of the bla1 and bla2 genes in an archetypal Bacillus anthracis strain is insufficient for penicillin resistance. In a penicillin-resistant clinical isolate, both genes are highly transcribed, but bla1 is the major contributor to high-level resistance to ampicillin. Differential expression of the bla genes is dependent upon strain background. Ciprofloxacin, doxycycline, and penicillin G are currently recommended by the Centers for Disease Control and Prevention and the Food and Drug Administration as therapeutics for inhalation and cutaneous anthrax (16). Prototypical Bacillus anthracis strains are susceptible to all three of these antibiotics. There have been no reports of naturally occurring ciprofloxacin- or doxycycline-resistant B. anthracis strains, but naturally occurring penicillin-resistant B. anthracis isolates have been reported (5, 19, 20, 32), and surveys of clinical and soil-derived strains have revealed penicillin G resistance in up to 16% of isolates tested (3, 6, 8, 10, 21, 25, 26).

The structural basis of cephalosporin formation in a mononuclear ferrous enzyme

Abstract: Deacetoxycephalosporin-C synthase (DAOCS) is a mononuclear ferrous enzyme that transforms penicillins into cephalosporins by inserting a carbon atom into the penicillin nucleus. In the first half-reaction, dioxygen and 2-oxoglutarate produce a reactive iron-oxygen species, succinate and CO2. The oxidizing iron species subsequently reacts with penicillin to give cephalosporin and water. Here we describe high-resolution structures for ferrous DAOCS in complex with penicillins, the cephalosporin product, the cosubstrate and the coproduct. Steady-state kinetic data, quantum-chemical calculations and the new structures indicate a reaction sequence in which a ‘booby-trapped’ oxidizing species is formed. This species is stabilized by the negative charge of succinate on the iron. The binding sites of succinate and penicillin overlap, and when penicillin replaces succinate, it removes the stabilizing charge, eliciting oxidative attack on itself. Requisite groups of penicillin are within 1 A of the expected position of a ferryl oxygen in the enzyme–penicillin complex.

Incidence of Carbapenem-Associated Allergic-Type Reactions among Patients with versus Patients without a Reported Penicillin Allergy

Abstract: This retrospective analysis sought to determine the comparative incidence of cross-reactivity associated with carbapenem antibiotic treatment among patients with versus those without penicillin allergy. We sought to determine whether the incidence of cross-reactivity is different between imipenem-cilastatin and meropenem. A total of 211 patients were treated with a carbapenem antibiotic. Included were 100 patients with and 111 patients without a documented or reported penicillin allergy. Within each group, subgroups of penicillin-allergic and penicillin-nonallergic patients were balanced equally between imipenem-cilastatin and meropenem. The incidence of patients with a reported or documented penicillin allergy experiencing an allergic-type reaction to a carbapenem was 11%, which is 5.2 times greater than the risk in patients who were reportedly not allergic to penicillin (P=.024). No difference in the occurrence of allergic-type reactions was observed between the 2 carbapenems.

Antimicrobial susceptibility of Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae collected from patients across the USA, in 2001-2002, as part of the PROTEKT US study.

Abstract: Background: The PROTEKT US (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin in the United States) surveillance programme was started in 2000, to chart the emergence and spread of antimicrobial resistance among isolates of Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae from across the USA. Methods: In 2001-2002 (Year 2 of PROTEKT US) 242 centres from 46 states and the territory of Puerto Rico submitted a total of 10012 S. pneumoniae, 4508 S. pyogenes and 3296 H. influenzae isolates from community-acquired respiratory tract infections (CARTIs). Susceptibility testing was performed and interpreted using NCCLS methodology and criteria. Results: Overall, 35.4% of S. pneumoniae were non-susceptible to penicillin (14.2% intermediate, MIC 0.12-1 mg/L; 21.2% resistant, MIC ≥2mg/L) and 27.9% were resistant to erythromycin (MIC ≥1 mg/L) (0.2% intermediate, MIC 0.5 mg/L). A total of 105 (1.0%) isolates were resistant to levofloxacin (MIC ≥8 mg/L). More than 99.2% of isolates were susceptible to telithromycin (MIC ≤1 mg/L) irrespective of penicillin and/or erythromycin resistance. All S. pyogenes isolates were susceptible to penicillin (MIC ≤0.12 mg/L) and 5.7% were resistant to erythromycin (MIC ≥1 mg/L) (0.3% intermediate, MIC 0.5 mg/L). The MICA of telithromycin for S. pyogenes was 0.03 mg/L. A total of 27.5% of H. influenzae isolates were β-lactamase producers. Overall, 27.8% were resistant (MIC ≥4 mg/L) and 1.1% were intermediate to ampicillin (MIC 2 mg/L). A total of 96.3% of H. influenzae isolates were susceptible to telithromycin (MIC ≤4 mg/L). Conclusions: Antimicrobial resistance continues to be a problem in the USA. The ketolide telithromycin continues to show high activity against common CARTI pathogens, including those resistant to β-lactams and macrolides.

Is it safe to use carbapenems in patients with a history of allergy to penicillin

Abstract: Objectives The purpose of this retrospective study was to ascertain the clinical safety of administering carbapenems, namely imipenem/cilastatin and meropenem, in patients with a history of penicillin allergy compared with administering carbapenems in patients with no reported penicillin allergy. Carbapenems are similar in chemical structure to the penicillins and therefore are associated with a risk for allergic cross-hypersensitivity. Carbapenems are commonly avoided in patients with a reported penicillin allergy on the basis of a potential cross-hypersensitivity with penicillin, however, very few studies have been conducted describing the incidence of cross-hypersensitivity between penicillin and carbapenems. Methods A retrospective review was conducted in a total of 266 patients who were administered either imipenem/cilastatin or meropenem. The patients were admitted to the Cleveland Clinic Health System--Eastern Region Hospitals during the years 2001 and 2002. Results Fifteen of the 163 patients (9.2%) with reported penicillin allergy developed a hypersensitivity reaction to meropenem or imipenem/cilastatin whereas 3.9% of the 103 patients without penicillin allergy developed a hypersensitivity reaction to meropenem or imipenem/cilastatin. These results are not statistically significant. Conclusions Based on this study and other similar studies, the true incidence of cross-hypersensitivity reactions between penicillin and carbapenems may be lower than previously reported. Carbapenem use may be reasonable for penicillin allergic patients if caution is exercised.

Pre-exposure of infected human endometrial epithelial cells to penicillin in vitro renders Chlamydia trachomatis refractory to azithromycin

Abstract: Objective: The clinical significance of the potential for persistent human chlamydial infections in vivo is being actively reassessed because of the increased frequency of recurrent infection with the same serovar despite compliance with an effective antibiotic regimen. The ability to extend the length of time of in vitro cultivation of polarized human endometrial epithelial cells (HEC-1 B) provided the opportunity to establish a model system to determine if a persistent form of Chlamydia trachomatis had the same susceptibility as the actively growing form to a cidal concentration of azithromycin. Methods: Polarized HEC-1B cells cultivated on extracellular matrix were Infected with C. trachomatis serovar E and exposed to penicillin at 24h post-infection (hpi) to Induce a persistent Infection characterized by slowly metabolizing but non-dividing, ultrastructurally aberrant reticulate bodies within the chlamydial inclusion; at 48 hpi, infected cultures were exposed to a bactericidal concentration of azithromycin for 72 h. Results: Persistent chlamydiae were phenotypically resistant to azithromycin; the number of chlamydial inclusions on subpassage of progeny from persistent chlamydiae following removal of penicillin and recovery was essentially the same as from progeny from persistent chlamydiae following removal of penicillin and azithromycin and recovery. Neutrophils were attracted in vitro to persistently infected HEC-1B cells that had been exposed to penicillin and azithromycin. Conclusions: Thus, this study provides evidence at the cellular microbiology level in vitro for mechanisms that could exist in vivo to create sustained, but perhaps clinically inapparent inflammation, which might eventually lead to conditions such as silent pelvic inflammatory disease.

Trends in Antimicrobial Resistance in 1,968 Invasive Streptococcus pneumoniae Strains Isolated in Spanish Hospitals (2001 to 2003): Decreasing Penicillin Resistance in Children's Isolates

Abstract: To address the public health problem of antibiotic resistance, the European Union (EU) founded the European Antimicrobial Resistance Surveillance System. A network of 40 hospitals that serve approximately 30% of the Spanish population (about 12 million) participated. Each laboratory reported data on antimicrobial susceptibility testing using standard laboratory procedures that were evaluated by an external quality control program. The antibiotic consumption data were obtained from the National Health System. We compared the antibiotic susceptibility of Spanish isolates of invasive Streptococcus pneumoniae (2001 to 2003) with antibiotic consumption. Invasive S. pneumoniae was isolated from 1,968 patients, 20% of whom were children at or below the age of 14 years. Of non-penicillin-susceptible strains (35.6%; 95% confidence interval, 34 to 37.2), 26.4% were considered intermediate and 9.2% were considered resistant. Between 2001 and 2003, penicillin resistance decreased from 39.5 to 33% overall and from 60.4 to 41.2% in children at or below the age of 14 years (P = 0.002). Resistance to erythromycin was at 26.6%, and coresistance with penicillin was at 19.1%. Of total isolates, the ciprofloxacin MIC was >2 μg/ml for 2.1%, with numbers increasing from 0.4% (2001) to 3.9% (2003). Total antibiotic use decreased from 21.66 to 19.71 defined daily doses/1,000 inhabitants/day between 1998 and 2002. While consumption of broad-spectrum penicillins, cephalosporins, and erythromycin declined, use of amoxicillin-clavulanate and quinolones increased by 17.5 and 27%, respectively. The frequency of antibiotic resistance in invasive S. pneumoniae in Spain was among the highest in the EU. However, a significant decrease in penicillin resistance was observed in children. This decrease coincided with the introduction of a heptavalent conjugate pneumoccocal vaccine (June 2001) and with a global reduction in antibiotic consumption levels.

Fluoroquinolone resistance in penicillin-resistant Streptococcus pneumoniae Clones, Spain

Abstract: Among 2,882 Streptococcus pneumoniae sent to the Spanish Reference Laboratory during 2002, 75 (2.6%) were ciprofloxacin-resistant. Resistance was associated with older patients (3.9% in adults and 7.2% in patients ≥65 years of age), with isolation from noninvasive sites (4.3% vs. 1.0%), and with penicillin and macrolide resistance. Among 14 low-level resistant (MIC 4–8 µg/mL) strains, 1 had a fluoroquinolone efflux phenotype, and 13 showed single ParC changes. The 61 high-level ciprofloxacinresistant (MIC ≥16 µg/mL) strains showed either two or three changes at ParC, ParE, and GyrA. Resistance was acquired either by point mutation (70 strains) or by recombination with viridans streptococci (4 strains) at the topoisomerase II genes. Although 36 pulsed-field gel electrophoresis patterns were observed, 5 international multiresistant clones (Spain 23F -1, Spain 6B -2, Spain 9V -3, Spain14-5 and Sweden15A-25) accounted for 35 (46.7%) of the ciprofloxacin-resistant strains. Continuous surveillance is needed to prevent the dissemination of these clones.

Determination of beta-lactams in milk using a surface plasmon resonance-based biosensor.

Abstract: Two surface plasmon resonance (SPR)-based biosensor assays for detection of beta-lactam antibiotics in milk are reported. The assays are based on the enzymatic activity of a carboxypeptidase converting a 3-peptide into a 2-peptide, a reaction that is inhibited in the presence of beta-lactams. Antibodies were used to measure either the amount of formed enzymatic product or the amount of remaining enzymatic substrate. Both assays detected different beta-lactams at or below European maximum residue limits (MRLs), and the detection limit for penicillin G was 1.2 microg/kg and 1.5 microg/kg for the 2- and 3-peptide assays, respectively. The precision (CV) was < 5%, both within and between assays at the penicillin G MRL (4 microg/kg). The biosensor results obtained upon analysis of incurred milk samples were compared with results obtained by liquid chromatography (HPLC), and the method agreements were, in general, good.

Daptomycin - a novel antibiotic against Gram-positive pathogens.

Abstract: Daptomycin is a novel member of a new class of antimicrobial agents used in treating resistant Gram-positive infections. These infections are becoming more commonplace and treatment options are limited. At present, daptomycin is approved for use in the US for complicated skin and skin-structure infections that are a common complication of surgery, diabetic foot ulcers, and burns. The most common causative organisms in these types of infections are Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Group C and G streptococci. Traditionally, these infections have been treated with penicillin and cephalosporins, but resistance to these agents is widespread and increasing. Of particular concern is the rapid increase in methicillin-resistant S. aureus (MRSA). The SENTRY Antimicrobial Surveillance Programme reported that approximately 30% of S. aureus isolates from skin and skin-structure infections were MRSA. The standard treatment for MRSA infections is vancomycin but resistance to this agent is also developing. There is a continuing need for the development of new antibiotics with Gram-positive activity, to combat multi-drug-resistant Gram-positive infections.

Antimicrobial Susceptibility Patterns among Viridans Group Streptococcal Isolates from Infective Endocarditis Patients from 1971 to 1986 and 1994 to 2002

Abstract: To determine whether changes in antimicrobial resistance have occurred among viridans group streptococci, we retrospectively examined 50 viridans group streptococcal isolates recovered from patients with infective endocarditis over 3 decades. Resistance rates (percent resistant isolates 1971 to 1986 and 1994 to 2002) were as follows: levofloxacin, 0 and 9; penicillin and clindamycin, 0 and 4; and erythromycin and azithromycin, 11 and 26, respectively.

Meta-analysis of Cephalosporins versus Penicillin for Treatment of Group A Streptococcal Tonsillopharyngitis in Adults

Abstract: We conducted a meta-analysis of 9 randomized controlled trials (involving 2113 patients) comparing cephalosporins with penicillin for treatment of group A beta -hemolytic streptococcal (GABHS) tonsillopharyngitis in adults. The summary odds ratio (OR) for bacteriologic cure rate significantly favored cephalosporins, compared with penicillin (OR,1.83; 95% confidence interval [CI], 1.37-2.44); the bacteriologic failure rate was nearly 2 times higher for penicillin therapy than it was for cephalosporin therapy (P=.00004). The summary OR for clinical cure rate was 2.29 (95% CI, 1.61-3.28), significantly favoring cephalosporins (P<.00001). Sensitivity analyses for bacterial cure significantly favored cephalosporins over penicillin in trials that were double-blinded and of high quality, trials that had a well-defined clinical status, trials that performed GABHS serotyping, trials that eliminated carriers from analysis, and trials that had a test-of-cure culture performed 3-14 days after treatment. This meta-analysis indicates that the likelihood of bacteriologic and clinical failure in the treatment of GABHS tonsillopharyngitis is 2 times higher for oral penicillin than for oral cephalosporins.