Showing papers on "Penicillin published in 1999"

Biodegradability of cefotiam, ciprofloxacin, meropenem, penicillin G, and sulfamethoxazole and inhibition of waste water bacteria

Abstract: Most antibiotics are metabolized only incompletely by patients after administration and enter the municipal sewage with the patients' excretions. Little is known about their biodegradability in aquatic environments and their role with respect to growing bacterial resistance. Therefore, the biodegradability of some clinically important antibiotic drugs as a very first step of an environmental risk assessment was investigated with the OECD closed bottle test (CBT). To assess toxicity of the test compounds against aquatic bacteria (1) a growth inhibition test (GIT) with Pseudomonas putida was conducted; (2) a toxicity control was used in the CBT; and (3) the colony-forming units (CFUs) were monitored in the test vessels. Theoretical concentrations of the test substances in hospital effluents were calculated and compared with minimum inhibitory concentrations for susceptible pathogenic bacteria. None of the test compounds met the criteria for ready biodegradability. Only penicillin G was biodegradable to some degree (27%), even when the test was prolonged from 28 to 40 days (35%). The inhibition concentrations measured in the GIT were in the same range or lower than the 50% minimum inhibitory concentrations (MIC50) known for susceptible pathogenic bacteria. CFU monitoring revealed high toxicity for sulfamethoxazole, whereas ciprofloxacin had a weak but significant effect; only for meropenem a weak but significant effect was measured in the toxicity control of the CBT. MIC50 published for susceptible pathogenic bacteria were for all compounds in the same range as the concentrations expected for hospital effluents. Therefore, antibiotic drugs emitted into municipal sewage may affect the biological process in sewage treatment plants (STPs), and they may persist in the aquatic environment and contribute to the increasing resistance of pathogenic bacteria.http://link.springer-ny. com/link/service/journals/00244/bibs/37n2p158.html

Susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae to 10 Oral Antimicrobial Agents Based on Pharmacodynamic Parameters: 1997 U.S. Surveillance Study

Abstract: The susceptibilities of Streptococcus pneumoniae (1,476 strains) and untypeable Haemophilus influenzae (1,676 strains) to various oral β-lactam, macrolide-azalide, and fluoroquinolone antimicrobial agents were determined by broth microdilution. Organisms were isolated from specimens obtained from outpatients in six geographic regions of the United States. MIC data were interpreted according to pharmacodynamically derived breakpoints applicable to the oral agents tested. Among H. influenzae strains, 41.6% were β-lactamase positive. Virtually all H. influenzae strains were susceptible to amoxicillin-clavulanate (98%), cefixime (100%), and ciprofloxacin (100%), while 78% were susceptible to cefuroxime, 57% were susceptible to amoxicillin, 14% were susceptible to cefprozil, 9% were susceptible to loracarbef, 2% were susceptible to cefaclor, and 0% were susceptible to azithromycin and clarithromycin. Among S. pneumoniae isolates, 49.6% were penicillin susceptible, 17.9% were intermediate, and 32.5% were penicillin resistant, with penicillin MICs for 50 and 90% of the isolates tested of 0.12 and 4 μg/ml, respectively. Overall, 94% of S. pneumoniae isolates were susceptible to amoxicillin and amoxicillin-clavulanate, 69% were susceptible to azithromycin and clarithromycin, 63% were susceptible to cefprozil and cefuroxime, 52% were susceptible to cefixime, 22% were susceptible to cefaclor, and 11% were susceptible to loracarbef. Although ciprofloxacin has marginal activity against S. pneumoniae, no high-level fluoroquinolone-resistant strains were found. Significant cross-resistance was found between penicillin and macrolides-azalides among S. pneumoniae isolates, with 5% of the penicillin-susceptible strains being macrolide-azalide resistant, compared with 37% of the intermediate isolates and 66% of the resistant isolates. Resistance was highest in S. pneumoniae isolates from patients younger than 10 years of age, middle ear and paranasal sinus specimens, and the southern half of the United States. With the continuing rise in resistance, judicious use of oral antimicrobial agents is necessary in all age groups.

Resistance surveillance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in the United States, 1997-1998.

Abstract: A national antimicrobial resistance surveillance study was conducted from December 1997 to May 1998 to determine the prevalence of antimicrobial resistance in 6620 clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In this centralized study, which involved 163 institutions located in 43 states, we determined MICs for representatives of five antimicrobial classes: beta-lactams (penicillin, co-amoxiclav, cefuroxime, ceftriaxone), macrolides (azithromycin, clarithromycin), co-trimoxazole, glycopeptides (vancomycin) and fluoroquinolones (levofloxacin). In most S. pneumoniae isolates, all antimicrobials were to be found active, but amongst penicillin-resistant isolates (MICs > or = 2 mg/L), resistance to other beta-lactams, macrolides and co-trimoxazole was common. For vancomycin and levofloxacin, however, activity was not associated with penicillin resistance. The prevalence of penicillin-nonsusceptible (intermediate and resistant) pneumococci was highest in the South Atlantic (44%) and East South Central (43%) regions and lowest in the Mid-Atlantic (28%) and New England (28%) regions. Resistance to beta-lactams, macrolides and co-trimoxazole was more commonly found amongst respiratory isolates than blood isolates and in strains from patients < or = 12 years old than from older patients. beta-lactamase, which was detected in 33% of H. influenzae and 92% of M. catarrhalis strains, did not affect the activity of the beta-lactams under study other than ampicillin. Certain agents, such as vancomycin and the fluoroquinolones, remain highly active, and well-designed surveillance systems that monitor MIC distributions would be needed to detect a potential for reduced susceptibility. In addition, surveillance programmes should be designed to collect information about associated resistance as well as differences in prevalence associated with region, specimen source and patient age.

Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection.

Abstract: Context. Animal model studies have demonstrated the failure of penicillin to cure Streptococcus pyogenes myositis and have suggested that clindamycin is a more effective treatment. Objective. To determine the most effective antibiotic treatment for invasive S. pyogenes infection in humans. Design and setting. We conducted a retrospective review of the outcomes of all inpatients from 1983 to 1997 treated for invasive S. pyogenes infection at Children's Hospital. Patients. Fifty-six children were included, 37 with initially superficial disease and 19 with deep or multiple tissue infections. Main outcome measure. Lack of progression of disease (or improvement) after at least 24 h of treatment. Results. The median number of antibiotic exposures was 3 per patient (range 1 to 6) with clindamycin predominating in 39 of 45 courses of protein synthesis-inhibiting antibiotics and beta-lactams predominating amongst the cell wall-inhibiting antibiotics in 123 of 126 of the remainder. Clindamycin was often used in combination with a beta-lactam antibiotic. Overall there was a 68% failure rate of cell wall-inhibiting antibiotics when used alone. Patients with deep infection were more likely to have a favorable outcome if initial treatment included a protein synthesis-inhibiting antibiotic as compared with exclusive treatment with cell wall-inhibiting antibiotics (83% vs. 14%, P = 0.006) with a similar trend in those with superficial disease (83% vs. 48%, P = 0.07). For those children initially treated with cell wall-inhibiting antibiotics alone, surgical drainage or debridement increased the probability of favorable outcome in patients with superficial disease (100% vs. 41%, P = 0.04) with a similar trend in a smaller number of deep infections (100% vs. 0%, P = 0.14). Conclusions. This retrospective study suggests that clindamycin in combination with a beta-lactam antibiotic (with surgery if indicated) might be the most effective treatment for invasive S. pyogenes infection.

Natural evolution of skin test sensitivity in patients allergic to β- lactam antibiotics

Abstract: Background: Subjects with immediate reactions to penicillins and positive skin test responses may lose sensitivity if penicillin is avoided. The longer the interval between the reaction and the skin test, the greater the likelihood of having a negative result. Objective: We sought to study prospectively the evolution of skin test sensitivity in a group of subjects allergic to penicillin with positive skin test responses to different penicillin determinants. Methods: Skin tests were performed with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin (AX), and ampicillin at the initial evaluation and repeated 1, 3, and 5 years later if the responses were still positive. Subjects were divided into 2 groups. Group A consisted of patients with a positive skin test response to benzylpenicilloyl or minor determinant mixture, and group B consisted of those with a selective response to amoxicillin and good tolerance to benzylpenicillin. Results: In group A (n = 31) after 1 year, 25 patients continued to have positive responses and 6 began to have negative responses; after 3 years, 18 continued to have positive responses, 5 began to have negative responses, and 2 were lost to follow-up; and after 5 years, 12 continued to have positive responses, 5 began to have negative responses, and 1 was lost to follow-up. In group B (n = 24) 12 had positive responses, and 12 had negative responses after 1 year; 6 had positive responses, 5 had negative responses, and 1 was lost to follow-up after 3 years; and no patients had positive responses, 5 had negative responses, and 1 was lost to follow-up after 5 years. Survival analysis showed significant differences between groups (log-rank test=12.8; P Conclusion: Patients with a selective response to amoxicillin tended to lose sensitivity faster than those who responded to several penicillin determinants, supporting the existence of at least 2 distinct types of IgE response in patients allergic to β-lactam. (J Allergy Clin Immunol 1999;103:918-24.)

BOCILLIN FL, a Sensitive and Commercially Available Reagent for Detection of Penicillin-Binding Proteins

Abstract: Penicillin-binding proteins (PBPs) are the enzymes that are required for the biosynthesis of the bacterial cell wall (10, 11, 23, 31). PBPs catalyze the final steps of the polymerization (transglycosylation) and cross-linking (transpeptidation) of peptidoglycan, an essential component of the bacterial cell wall (10, 11, 23, 31). PBPs are membrane-bound enzymes and targets of β-lactam antibiotics (6, 7, 10, 11, 14, 24, 28–31). The emerging resistance of pathogenic gram-positive bacteria to β-lactam antibiotics is a serious clinical problem (6, 25, 29, 30). Resistance to β-lactam antibiotics in some species such as Streptococcus pneumoniae has occurred by development of altered high-molecular-mass PBPs which have reduced affinity for the antibiotics (6, 7, 10, 11, 14, 24, 25, 29, 30). Extensive molecular and genetic studies have been devoted to the understanding of the mechanisms of bacterial resistance to β-lactam antibiotics (6, 7, 10, 11, 25, 29, 30). PBPs have often been detected by labeling bacterial membrane preparations with 3H-, 14C-, or 125I-labeled penicillin, separating the labeled proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and exposing the gels to X-ray films (22, 27, 28). The major limitations of this type of methodology are time intensiveness (days to weeks), accumulation of hazardous materials, and lack of commercial availability. In this study, we describe a new, rapid, sensitive, and nonradioactive method for the detection and study of bacterial PBPs. This method involves the use of BOCILLIN FL (Fig. ​(Fig.1),1), a newly synthesized and commercially available fluorescent penicillin, as a labeling reagent (Molecular Probes, Inc., Eugene, Oreg.). The BOCILLIN FL-labeled PBPs were separated by SDS-PAGE and detected with a FluorImager or with the naked eye under UV light. FIG. 1 Structure of BOCILLIN FL.

Antimicrobial resistance with Streptococcus pneumoniae in the United States, 1997 98.

Abstract: From November 1997 to April 1998, 1,601 clinical isolates of Streptococcus pneumoniae were obtained from 34 U.S. medical centers. The overall rate of strains showing resistance to penicillin was 29. 5%, with 17.4% having intermediate resistance. Multidrug resistance, defined as lack of susceptibility to penicillin and at least two other non-ss-lactam classes of antimicrobial drugs, was observed in 16.0% of isolates. Resistance to all 10 ss-lactam drugs examined in this study was directly related to the level of penicillin resistance. Penicillin resistance rates were highest in isolates from middle ear fluid and sinus aspirates of children ambulatory-care settings. Twenty-four of the 34 medical centers in this study had participated in a similar study 3 years before. In 19 of these 24 centers, penicillin resistance rates increased 2.9% to 39.2%. Similar increases were observed with rates of resistance to other antimicrobial drugs.

Pneumonia Acquired in the Community Through Drug-Resistant Streptococcus pneumoniae

Abstract: The aim of the study was to determine the incidence of and risk factors for drug resistance of Streptococcus pneumoniae, and its impact on the outcome among hospitalized patients of pneumococcal pneumonia acquired in the community. Consecutive patients with culture-proven pneumococcal pneumonia were prospectively studied with regard to the incidence of pneumococcal drug resistance, potential risk factors, and in-hospital outcome variables. A total of 101 patients were studied. Drug resistance to penicillin, cephalosporin, or a macrolide drug was found in pneumococci from 52 of the 101 (52%) patients; 49% of these isolates were resistant to penicillin (16% intermediate resistance, 33% high resistance), 31% to cephalosporin (22% intermediate and 9% high resistance), and 27% to a macrolide drug. In immunocompetent patients, age > 65 yr was significantly associated with resistance to cephalosporin (odds ratio [OR]: 5.0; 95% confidence interval [CI]: 1.3 to 18.8, p = 0.01), and with the presence of > 2 comorbi...

Survey of susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates to 26 antimicrobial agents: a prospective U.S. study.

Abstract: An antimicrobial susceptibility surveillance study of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates was performed during the winter of 1996-1997 in order to determine their susceptibilities to 5 fluoroquinolones and 21 other antimicrobial agents. Broth microdilution MICs were determined for 2, 752 isolates from 51 U.S. medical centers. Of the 1,276 S. pneumoniae isolates, 64% were susceptible, 17% were intermediate, and 19% were highly resistant to penicillin. On the basis of the MICs at which 90% of isolates are inhibited and modal MICs, the hierarchy of the five fluoroquinolones from most to least active was grepafloxacin > sparfloxacin > levofloxacin = ciprofloxacin > ofloxacin. For S. pneumoniae isolates for which penicillin MICs were elevated, the MICs of the cephalosporins, macrolides, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole were also elevated, but the MICs of the fluoroquinolones, vancomycin, and rifampin were not. The prevalence of penicillin-susceptible pneumococci varied by U.S. Bureau of the Census region (range, 44% in the East South Central region to 75% in the Pacific region). In addition, S. pneumoniae isolates from blood were significantly more susceptible to penicillin than those from respiratory, ear, or eye specimens, and pneumococci from patients

Antimicrobial resistance of 1,113 Streptococcus pneumoniae isolates from patients with respiratory tract infections in Spain: results of a 1-year (1996-1997) multicenter surveillance study. The Spanish Surveillance Group for Respiratory Pathogens.

Abstract: A nationwide susceptibility surveillance of 1,113 Streptococcus pneumoniae isolates was carried out and found the following percentages of resistance: cefuroxime, 46%; penicillin, 37%; macrolides, 33%; aminopenicillins, 24%; cefotaxime, 13%; and ceftriaxone, 8%. A significant (P < 0.05) seasonality pattern for β-lactam antibiotics was observed. Resistance to macrolides was higher (P < 0.05) in middle-ear samples. Higher percentages of resistance to cefuroxime and macrolides were observed among penicillin-intermediate and -resistant strains, whereas high frequencies of resistance to aminopenicillins and expanded-spectrum cephalosporins were observed only among penicillin-resistant strains.

Penicillin Resistance and Other Predictors of Mortality in Pneumococcal Bacteremia in a Population With High Human Immunodeficiency Virus Seroprevalence

Abstract: Rates of invasive disease caused by penicillin-resistant pneumococci are rising. Previous reports have found no association between resistant pneumococci and increased mortality. To evaluate the impact of penicillin resistance and other variables on mortality, we retrospectively studied all cases of pneumococcal bacteremia identified by our microbiology laboratory from 1 January 1992 through 31 December 1996. There were 462 cases of pneumococcal bacteremia in 432 patients. The mean age was 35 years; 55% of the cases occurred in male patients, 58% were in black patients, and 40% were in Hispanic patients. One-half of the cases occurred in patients with documented human immunodeficiency virus (HIV) infection. Penicillin resistance was first noted in 1994 and increased yearly, accounting for 17% of 1996 isolates. Of all resistant isolates, 65% were resistant to penicillin at a high level. The overall mortality was 17%. On multivariate analysis, high-level penicillin resistance, older age, severe disease, multilobar infiltrates and/or effusion(s) on chest roentgenogram, and Hispanic ethnicity were independent predictors of mortality in pneumococcal bacteremia. In HIV-infected patients, a CD4 cell count below the median just missed statistical significance. This is the first report demonstrating penicillin resistance as an independent predictor of mortality among patients with pneumococcal bacteremia.

Risk Factors and Course of Illness Among Children With Invasive Penicillin-resistant Streptococcus pneumoniae

Abstract: Objectives To assess differences in risk factors, clinical presentation, and course of illness between children infected with penicillin-sensitive and drug-resistant Streptococcus pneumoniae (DRSP). Design A retrospective cohort study conducted in Uruguay and Argentina using information from a hospital-based surveillance system. Hospitalized children 5 years of age and younger who had S pneumoniae isolated from a normally sterile site between June 1993 and October 1996 were eligible. Hospital records were linked with surveillance data. Both stratified univariate analysis and logistic regression was completed. Results Of the 380 children eligible for the study, 274 records (72%) were available for review. Ninety-nine children (36%) had DRSP; 46 showed intermediate susceptibility (minimum inhibitory concentration, 0.12-1.0 microg/mL) and 53 showed high-level resistance (minimum inhibitory concentration >/=2.0 microg/mL). Children with meningitis were less likely to have DRSP than those with other forms of invasive disease (relative risk = 0. 5; 95% confidence interval [CI], 0.2-0.9). Risk factors associated with DRSP were use of penicillin or ampicillin in the 3 months before illness (odds ratio = 2.9; 95% CI, 1.5-5.7) and possession of private medical coverage (odds ratio = 2.4; 95% CI, 1.2-5.0). Response to therapy, including response to penicillin or ampicillin among children with nonmeningeal invasive disease, course of illness, and clinical outcome did not differ significantly between children infected with penicillin-susceptible or penicillin-resistant isolates. Conclusion In this study, previous use of penicillin or ampicillin and private medical coverage were associated with having DRSP. Children with nonmeningeal invasive disease responded equally well to penicillin regardless of the penicillin susceptibility of their pneumococcal isolate.

The Interaction and Transport of β-Lactam Antibiotics with the Cloned Rat Renal Organic Anion Transporter 1

Abstract: In the present study, we investigated the interactions between antibiotics, especially beta-lactam antibiotics, and rat renal organic anion transporter 1 (OAT1). [(14)C]p-Aminohippurate (PAH) uptake via OAT1 expressed in Xenopus laevis oocytes was inhibited by all of the penicillins and cephalosporins tested. Penicillin G, carbenicillin, cephaloridine, cephalothin, cefazolin, and cephalexin inhibited [(14)C]PAH uptake via OAT1 in a competitive manner (K(i) = 0.29-2.33 mM). Cinoxacin, a quinolone gyrase inhibitor, also inhibited PAH uptake via OAT1. Other antibiotics, such as gentamicin, streptomycin, and vancomycin, which do not contain anionic moieties, did not interact with OAT1. [(3)H]Penicillin G and [(14)C]cephaloridine were demonstrated to be transported via OAT1. Using the cells that stably expressed OAT1, we analyzed the cytotoxicity of several beta-lactam antibiotics. Cells expressing OAT1 showed higher susceptibility to cephaloridine (a potentially nephrotoxic beta-lactam antibiotic) toxicity than did control cells. The present study suggests that OAT1 is the major organic anion transporter in the kidney that is responsible for the renal secretion of antibiotics, especially that of beta-lactam antibiotics. Furthermore, the culture cell system expressing OAT1 was revealed to be useful for the prediction of the nephrotoxicity of beta-lactam antibiotics.

Susceptibility of group A beta-hemolytic streptococci to thirteen antibiotics: examination of 301 strains isolated in the United States between 1994 and 1997.

Abstract: Background. Because of continuing reports from many countries of increasing resistance of group A streptococci to macrolide antibiotics, we determined the antibiotic susceptibility of recent group A streptococcal isolates from the United States. Methods. We evaluated 301 Streptococcus pyogenes isolates (245 from patients with uncomplicated pharyngitis and 56 isolates from patients with invasive systemic infections) for susceptibility using the Etest technique. The isolates came from 24 states and the District of Columbia during the years 1994 through 1997. Thirteen antibiotics (azithromycin, ceftriaxone, cephalothin, chloramphenicol, ciprofloxacin, clindamycin, erythromycin, imipenem, levofloxacin, oxacillin, penicillin G, tetracycline and trimethoprim-sulfamethoxazole) were studied. Results. The MIC 90 for penicillin was 0.016 μg/ml, which is not significantly different from previous reports. Of the 301 isolates only 2.6% were resistant to a macrolide antibiotic and only 4% were resistant to tetracycline. Conclusions. These data indicate that antibiotic resistance among recent isolates of group A streptococci (including those from patients with severe infections) currently is not a clinically significant problem in the United States.

Carriage of respiratory tract pathogens and molecular epidemiology of Streptococcus pneumoniae colonization in healthy children attending day care centers in Lisbon, Portugal.

Abstract: In an effort to establish the rate of carriage of antibiotic resistant respiratory pathogens in children attending urban day care centers (DCC) in Portugal, seven DCC in Lisbon were selected for determining the rate of nasopharyngeal colonization of children between the ages of 6 months to 6 years by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Of the 586 children studied between January and March 1996, 47% carried S. pneumoniae, 72% H. influenzae, and 54% M. catarrhalis. Twenty-four percent of the pneumococci had reduced susceptibility to penicillin, and most of these belonged to serogroups 19, 23, 14, and 6. An additional 19% were fully susceptible to penicillin but showed decreased susceptibility to other antimicrobials. These isolates expressed serogroups 6, 11, 14, 18, 19, and 34. The majority (96%) of M. catarrhalis and 20% of H. influenzae were penicillin resistant due to the production of β-lactamases. Recent antimicrobial use was associated with carriage o...

In Vitro Antibacterial Activities of Platelet Microbicidal Protein and Neutrophil Defensin against Staphylococcus aureus Are Influenced by Antibiotics Differing in Mechanism of Action

Abstract: Thrombin-induced platelet microbicidal protein-1 (tPMP-1) and human neutrophil defensin-1 (HNP-1) are small, cationic antimicrobial peptides. These peptides exert potent in vitro microbicidal activity against a broad spectrum of human pathogens, including Staphylococcus aureus. Evidence suggests that tPMP-1 and HNP-1 target and disrupt the bacterial membrane. However, it is not yet clear whether membrane disruption itself is sufficient to kill the bacterium or whether subsequent, presumably intracellular, events are also involved in killing. We investigated the staphylocidal activities of tPMP-1 and HNP-1 in the presence or absence of pretreatment with antibiotics that differ in their mechanisms of action. The staphylocidal effects of tPMP-1 and HNP-1 on control cells (no antibiotic pretreatment) were rapid and concentration dependent. Pretreatment of S. aureus with either penicillin or vancomycin (bacterial cell wall synthesis inhibitors) significantly enhanced the anti-S. aureus effects of tPMP-1 compared with the effects against the respective control cells over the entire tPMP-1 concentration range tested (P < 0.05). Similarly, S. aureus cells pretreated with these antibiotics were more susceptible to HNP-1 than control cells, although the difference in the effects against cells that received penicillin pretreatment did not reach statistical significance (P < 0.05 for cells that received vancomycin pretreatment versus effects against control cells). Studies with isogenic pairs of strains with normal or deficient autolytic enzyme activities demonstrated that enhancement of S. aureus killing by cationic peptides and cell wall-active agents could not be ascribed to a predominant role of autolytic enzyme activation. Pretreatment of S. aureus cells with tetracycline, a 30S ribosomal subunit inhibitor, significantly decreased the staphylocidal effect of tPMP-1 over a wide peptide concentration range (0.16 to 1.25 μg/ml) (P < 0.05). Furthermore, pretreatment with novobiocin (an inhibitor of bacterial DNA gyrase subunit B) and with azithromycin, quinupristin, or dalfopristin (50S ribosomal subunit protein synthesis inhibitors) essentially blocked the S. aureus killing resulting from exposure to tPMP-1 or HNP-1 at most concentrations compared with the effects against the respective control cells (P < 0.05 for a tPMP-1 concentration range of 0.31 to 1.25 μg/ml and for an HNP-1 concentration range of 6.25 to 50 μg/ml). These findings suggest that tPMP-1 and HNP-1 exert anti-S. aureus activities through mechanisms involving both the cell membrane and intracellular targets.

Prevalence of resistance to MLS antibiotics in 20 European university hospitals participating in the European SENTRY surveillance programme

Abstract: Macrolide, lincosamide and streptogramin (MLS) antibiotics are chemically distinct inhibitors of bacterial protein synthesis. Resistance to MLS antibiotics may be constitutive or inducible. The purpose of this study is to update our understanding of the prevalence of different forms of MLS resistance in Europe. The analysis of 3653 clinical pneumococcal, staphylococcal and enterococcal isolates exhibited an average percentage of 21.3% and 6.2% intermediate and high-level penicillin-resistant Streptococcus pneumoniae, 21.8% methicillin-resistant S t a p h y l o- coccus aureus and 11% vancomycin-resistant Enterococcus faecium. Geographical differ- ences in erythromycin and clindamycin resistance in isolates of S. pneumoniae and S. aureus strongly reflect geographical variations in susceptibility to penicillin and methicillin, respec- tively. A very narrow range of MICs was obtained with quinupristin/dalfopristin, with no S. pneumoniae, S. aureus and E. faecium isolate having an MIC of >4 mg/L, indicating a possible role of quinupristin/dalfopristin in the treatment of infections by multi-resistant Gram-positive bacteria.

Prevalence and mechanisms of macrolide resistance in clinical isolates of group A streptococci from Ontario, Canada.

Abstract: A total of 3,205 group A streptoccal isolates were collected in 1997 through a private laboratory which serves community physicians in southern Ontario and which represents a population base of 6 million people. Nonsusceptibility to erythromycin was detected for 67 (2.1%) isolates both by disk diffusion and by broth microdilution. Of these, 47 (70%) were susceptible to clindamycin and were found by PCR to possess the mef gene. Of the other 20 strains, 18 and 2 showed inducible and constitutive resistance, respectively, to clindamycin. Nineteen of these strains were shown by PCR to possess the ermTR gene, and a single constitutively resistant strain harbored an ermB gene. Sixteen (24%) erythromycin-resistant strains were also resistant to tetracycline. All were susceptible to penicillin and chloramphenicol.

Identification and antibiotic susceptibility of coagulase negative staphylococci isolated in corneal/external infections

Abstract: AIMS—To identify and determine antibiotic susceptibility of coagulase negative staphylococci (CoNS) isolated from patients with chronic blepharitis, purulent conjunctivitis, and suppurative keratitis. METHODS—A retrospective review of all culture positive cases of chronic blepharitis, purulent conjunctivitis, and suppurative keratitis between July 1995 and December 1996 was performed. Cases in which CoNS were the sole isolates were analysed. Species identification was performed by using a commercially available standardised biochemical test system. Antibiotic susceptibility to penicillin, gentamicin, tetracycline, erythromycin, ciprofloxacin, and teicoplanin was determined by agar disc diffusion (Kirby-Bauer method). Teicoplanin resistance was confirmed by agar dilution. RESULTS—42 Staphylococcus epidermidis, four S warneri, three S capitis, two S hominis, one each of S xylosus, S simulans, S equorum, and S lugdunensis were identified. 37 CoNS were penicillin resistant, 12 gentamicin resistant, 28 tetracycline resistant, 18 erythromycin resistant, four ciprofloxacin resistant, and one teicoplanin resistant (MIC, 32 µg/ml). In total, 16 strains were resistant to three or more antibiotics. CONCLUSION—Species of CoNS apart from S epidermidis may be isolated from patients with corneal and external infection. Antibiotic susceptibility of CoNS is unpredictable and multiresistant strains are common. As a result, antibiotic susceptibility testing should be performed in all cases of clinically significant ocular infections caused by CoNS.

Molecular Relationships and Antimicrobial Susceptibilities of Viridans Group Streptococci Isolated from Blood of Neutropenic Cancer Patients

Abstract: Viridans group streptococci, part of the normal human commensal flora, have emerged as important pathogens causing bacteremia and sepsis in neutropenic cancer patients (3–5, 7, 9, 12, 14). Clinical manifestations of viridans group streptococcal bacteremia may include fever, hypotension, shock, pneumonia, and adult respiratory distress syndrome, with a mortality rate ranging between 6 and 30% (6). The species most frequently isolated from blood cultures of neutropenic patients are Streptococcus mitis, Streptococcus oralis and Streptococcus sanguis (5, 8, 12, 28). The increased frequency of these infections has been attributed to several factors, including high-dose chemotherapy with cytosine arabinoside, oropharyngeal mucositis, and prophylactic therapy with cotrimoxazole or a fluoroquinolone (5, 11, 12, 17, 28, 30). Protective factors have included the early administration of parenteral antibiotics during febrile neutropenia and the prophylactic administration of penicillin (6). Oral and gastrointestinal mucosal lesions and intravascular catheters have been suggested as the most frequent portals of entry (5, 12, 14, 28). In the past, viridans group streptococci were considered to be uniformly susceptible to β-lactam antimicrobial agents, macrolides, and tetracyclines. However, the emergence of strains resistant to β-lactams and other antibiotics is a cause of concern and could compromise currently used prophylactic and therapeutic antibiotic regimens (8, 10, 22, 25). In one recent study, after the introduction of penicillin prophylaxis, resistance to penicillin increased from 0% in 1989 to more than 80% in 1994 (19). Viridans group streptococcal bacteremia in both immunocompetent and immunocompromised patients is usually considered to be of endogenous origin. There are, however, limited data based on modern molecular typing methods to support this hypothesis. The purpose of this study was to investigate the molecular epidemiology and antimicrobial susceptibilities of viridans group streptococci isolated from the blood of neutropenic patients with hematologic malignancies. The possible impact of patient-to-patient transmission of these organisms was studied by randomly amplified polymorphic DNA (RAPD) analysis and analysis of genomic DNA by pulsed-field gel electrophoresis (PFGE). (This work was presented in part at the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, Calif., 24 to 27 September 1998 [31].)

Azithromycin compared with penicillin G benzathine for treatment of incubating syphilis.

Abstract: A single 1.0-g dose of azithromycin seems to be efficacious for preventing syphilis in the sexual partners of infected persons.

Comparison of the supplemental effects of Saccharomyces cerevisiae and antibiotics in low‐protein and high‐fibre diets fed to broiler chickens

Abstract: Two experiments were completed to compare the supplemental effects of yeast Saccharomyces cerevisiae and sub‐therapeutic antibiotics in high‐fibre and low‐protein diets for broiler chicks. In experiment I, yeast was added at 1.5, 3.0 and 6.0gkg‐1 while penicillin, tylosin or neoterramycin were added at 150 mg kg‐1 into different batches of a high‐fibre diet containing 250 g kg‐1 palm kernel meal. Saccharomyces cerevisiae and antibiotics increased BW, BWG, FCR, feed intake, carcass and breast weights above the control. Small intestine weight was reduced by antibiotics, while yeast caused a lower deposition of abdominal fat. Liver weights of different treated broilers were similar. The performance indices were superior on penicillin and 3.0 g kg‐1 yeast compared to other supplements evaluated. In the second experiment, 1.5 and 3.0 g kg‐1 of yeast, and 0.75 mg kg‐1 of procaine penicillin, zinc bacitracin and tylosin were separately added to a 180 g kg‐1 crude protein diet. Performance of the chicks with addi...

Extremely high incidence of macrolide and trimethoprim-sulfamethoxazole resistance among clinical isolates of Streptococcus pneumoniae in Taiwan.

Abstract: From January 1996 to December 1997, 200 isolates of Streptococcus pneumoniae recovered from 200 patients treated at National Taiwan University Hospital were serotyped and their susceptibilities to 16 antimicrobial agents were determined by the agar dilution method. Sixty-one percent of the isolates were nonsusceptible to penicillin, exhibiting either intermediate resistance (28%) or high-level resistance (33%). About two-fifths of the isolates displayed intermediate or high-level resistance to cefotaxime, ceftriaxone, cefepime, imipenem, and meropenem. Extremely high proportions of the isolates were resistant to erythromycin (82%), clarithromycin (90%), and trimethoprim-sulfamethoxazole (TMP-SMZ) (87%). Among the isolates nonsusceptible to penicillin, 23.8% were resistant to imipenem; more than 60% displayed resistance to cefotaxime, ceftriaxone, cefepime, and carbapenems; 96.7% were resistant to erythromycin; and 100% were resistant to TMP-SMZ. All isolates were susceptible to rifampin and vancomycin. The MICs at which 50% and 90% of the isolates were inhibited were 0.12 and 1 microgram/ml, respectively, for cefpirome, and 0.12 and 0.25 microgram/ml, respectively, for moxifloxacin. Six serogroups or serotypes (23F, 19F, 6B, 14, 3, and 9) accounted for 77.5% of all isolates. Overall, 92.5% of the isolates were included in the serogroups or serotypes represented in the 23-valent pneumococcal vaccine. The incidence of macrolide and TMP-SMZ resistance for S. pneumoniae isolates in Taiwan in this study is among the highest in the world published to date.

Nationwide Survey in Italy of Treatment of Streptococcus pyogenes Pharyngitis in Children: Influence of Macrolide Resistance on Clinical and Microbiological Outcomes

Abstract: Throat swab specimens were obtained from 3,227 children with symptoms of acute pharyngotonsillitis. After 14 to 21 days, a second throat swab specimen was obtained at a follow-up visit. Over 42% of the 934 strains of Streptococcus pyogenes isolated in the primary study were resistant to erythromycin, azithromycin, and clarithromycin. Eradication rates among the 668 patients who entered the follow-up study were as follows: 84.1%, penicillin recipients; 82.7%, cephalosporin recipients; and 71.7%, macrolide recipients. Among patients treated with macrolides, the eradication rate was ∼80% when the infecting organisms were erythromycin-susceptible and ∼60% when they were erythromycin-resistant. These results indicate substantial in vitro macrolide resistance among Italian isolates of S. pyogenes. However, at least for a minor self-limiting condition such as acute S. pyogenes pharyngitis, our findings point to a limited overall correlation between in vitro susceptibility (to penicillins, cephalosporins, or macrolides) and eradication in patients treated with these drugs and an even weaker correlation between in vitro resistance (to macrolides) and noneradication in patients receiving macrolide therapy.

Pharmacodynamics of Vancomycin for the Treatment of Experimental Penicillin- and Cephalosporin-Resistant Pneumococcal Meningitis

Abstract: With the emergence of β-lactam antibiotic resistance among strains of Streptococcus pneumoniae, vancomycin has assumed an important role in the treatment of bacterial meningitis. Using the rabbit meningitis model, we evaluated the pharmacokinetics and pharmacodynamics of vancomycin in this setting. Animals were given 80 mg/kg of body weight daily in two or four divided doses to determine the penetration and activity of vancomycin in cerebrospinal fluid (CSF); each regimen was administered with and without dexamethasone. Mean peak (2 h) concentrations in CSF that were four- to eightfold higher than the minimum bactericidal concentration (MBC; 0.5 μg/ml) for the pathogen were adequate for bacterial clearance. In both groups concentrations in CSF remained higher than the MBC for greater than 80% of the respective dosing intervals, and the penetration of vancomycin into CSF was 20%. Mean concentrations in CSF at 24 to 36 h of therapy were lower than those achieved during the first 12 h, consistent with a decline in the level of antibiotic entry into CSF as inflammation wanes. Rates of bacterial clearance were similar for the two regimens, and for all animals cultures of CSF were sterile by 36 h. The coadministration of dexamethasone significantly reduced the penetration of vancomycin into CSF by 29% and significantly lowered the rate of bacterial clearance during the first 6 h in animals receiving 20-mg/kg doses of vancomycin. For animals receiving 40-mg/kg doses, therapeutic peak concentrations in CSF were obtained even with steroid use, suggesting that the effect of steroids may be circumvented by the use of larger daily doses of vancomycin.