Showing papers on "Penicillin published in 1998"

Three-Year Multicenter Surveillance of Pneumococcal Meningitis in Children: Clinical Characteristics, and Outcome Related to Penicillin Susceptibility and Dexamethasone Use

Abstract: Objectives. To evaluate the antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from the blood and cerebrospinal fluid of children with meningitis. To describe and compare the clinical and microbiological characteristics, treatment, and outcome of children with meningitis caused by S pneumoniae based on antimicrobial susceptibility of isolates and the administration of dexamethasone. Design and Patients. Children with pneumococcal meningitis were identified from among a group of patients with systemic infections caused by S pneumoniae who were enrolled prospectively in the United States Pediatric Multicenter Pneumococcal Surveillance Study at eight children9s hospitals in the United States. From September 1, 1993 to August 31, 1996, 180 children with 181 episodes of pneumococcal meningitis were identified and data were collected by retrospective chart review. Outcome. Clinical and laboratory characteristics were assessed. All pneumococcal isolates were serotyped and antibiotic susceptibilities for penicillin and ceftriaxone were determined. Clinical presentation, hospital course, and outcome parameters at discharge were compared between children infected with penicillin-susceptible isolates and those with nonsusceptible isolates and for children who did and did not receive dexamethasone. Results. Fourteen (7.7%) of 180 children died; none of the fatalities were because of a documented failure of treatment caused by a resistant strain. Only 1 child, who had mastoiditis and a lymphangioma, experienced a bacteriologic failure with a penicillin-resistant (minimum inhibitory concentration = 2 μg/mL) organism. Of the 166 surviving children, 41 (25%) developed neurologic sequelae (motor deficits) and 48 (32%) of 151 children had unilateral (n = 26) or bilateral (n = 22) moderate to severe hearing loss at discharge. Overall, 12.7% and 6.6% of the pneumococcal isolates were intermediate and resistant to penicillin and 4.4% and 2.8% were intermediate and resistant to ceftriaxone, respectively. Clinical presentation, cerebrospinal fluid indices on admission, and hospital course, morbidity, and mortality rates were similar for patients infected with penicillin- or ceftriaxone-susceptible versus nonsusceptible organisms. However, the relatively small numbers of nonsusceptible isolates and the inclusion of vancomycin in the treatment regimen for the majority of the patients limit the power of this study to detect significant differences in outcome between patients infected with susceptible and nonsusceptible isolates. Nonetheless, our results show that the nonsusceptible organisms do not seem to be intrinsically more virulent. Forty children (22%) received dexamethasone (≥8 doses) initiated before or within 1 hour after the first dose of antibiotics. The incidence of any moderate or severe hearing loss was significantly higher in the dexamethasone group (46%) compared with children not receiving any dexamethasone (23%). The incidence of any neurologic deficits, including hearing loss, also was significantly higher in the dexamethasone group (55% vs 33%). However, children in the dexamethasone group more frequently required intubation and mechanical ventilation and had lower initial concentration of glucose in the cerebrospinal fluid than children who did not receive any dexamethasone. When we controlled for the confounding factor, severity of illness (intubation), the incidence of any deafness and of any neurologic sequelae, including deafness, were no longer significantly different between children who did or did not receive dexamethasone. Conclusions. Children with pneumococcal meningitis caused by penicillin- or ceftriaxone-nonsusceptible organisms and those infected by susceptible strains had similar clinical presentation and outcome. The use of dexamethasone was not associated with a beneficial effect in this retrospective and nonrandomized study. Only a well-designed, prospective, randomized, placebo-controlled study, conducted in centers where optimal supportive care can be provided, will determine the potential benefit, if any, of dexamethasone in patients with pneumococcal meningitis.

Synthesis and Antibacterial Activity of Ketolides (6-O-Methyl-3-oxoerythromycin Derivatives): A New Class of Antibacterials Highly Potent Against Macrolide-Resistant and -Susceptible Respiratory Pathogens†

Abstract: In the search for new antibiotics active against macrolide-resistant pneumococci and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O-methylerythromycin derivatives, so-called "ketolides" A keto function was introduced in position 3 after removal of L-cladinose, a sugar which has long been thought essential Further modifications of the macrolactone backbone allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11, 12-hydrazonocarbamate ketolides These compounds were found to be very active against penicillin/erythromycin-resistant pneumococci and noninducers of MLSB resistance The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent activity against multiresistant pneumococci associated with a well-balanced activity against all bacteria involved in respiratory infections including H influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria In addition HMR 3004 displayed high therapeutic activity in animals infected by all major strains, irrespective of their resistance phenotype

Three-year multicenter surveillance of systemic pneumococcal infections in children

Abstract: Objective. To track antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from children with systemic infections and determine outcome of treatment. Design. A 3-year (September 1993 through August 1996) prospective surveillance study of all invasive pneumococcal infections in children. Patients. Infants and children cared for at eight children's hospitals in the United States with culture-proven systemic pneumococcal infection. Results. One thousand two hundred ninety-one episodes of systemic pneumococcal infection were identified in 1255 children. An underlying illness was present in the children for 27% of the episodes. The proportion of isolates that were nonsusceptible to penicillin or ceftriaxone increased annually and nearly doubled throughout the 3-year period; for the last year the percentages of isolates nonsusceptible to penicillin and ceftriaxone were 21% and 93%, respectively. There was no difference in mortality between patients with penicillin-susceptible or nonsusceptible isolates. Only 1 of 742 patients with bacteremia had a repeat blood culture that was positive >1 day after therapy was started. All 24 normal children with bacteremia attributable to isolates resistant to penicillin had resolution of their infection; the most common treatment regimen was a single dose of ceftriaxone followed by an oral antibiotic. Conclusions. The percentage of pneumococcal isolates nonsusceptible to penicillin and ceftriaxone increased yearly among strains recovered from children with systemic infection. Because empiric antibiotic therapy already has changed for suspected pneumococcal infections, antibiotic resistance has not been associated with increased mortality. Careful monitoring of antibiotic susceptibility and outcome of therapy is necessary to continually reassess current recommendations for treatment. Pediatrics 1998;102:538-545; Streptococcus pneumoniae, antibiotic resistance, outcome.

Acquisition, Carriage, and Transmission of Pneumococci with Decreased Antibiotic Susceptibility in Young Children Attending a Day Care Facility in Southern Israel

Abstract: The prevalence and transmission of antimicrobial drug-resistant pneumococci was studied in 48 children attending a day care facility in southern Israel. Nasopharyngeal cultures were obtained every 2 weeks for 10 months, and antibiotic susceptibility of isolates was determined by disk diffusion and E-test. Relatedness of isolates was investigated by capsular typing, ribotyping, and arbitrarily primed polymerase chain reaction. Pneumococci were recovered during 362 (63%) of 573 fortnights, and 219 (60%) of these isolates showed decreased susceptibility to at least one drug; 154 (43%) were intermediately susceptible to penicillin and 51 (14%) were multiresistant. Combining the different typing methods showed that a limited number of clones circulated in the facility. Clones exhibiting decreased antibiotic susceptibility (especially 23F, intermediately susceptible to penicillin and resistant to trimethoprim-sulfamethoxazole, and multiresistant 6B) were more frequently isolated and persisted longer than did fully susceptible clones. By multivariate analysis, carriage of organisms with decreased antibiotic susceptibility was associated with young age, female sex, winter season, and exposure to antimicrobial drugs during the previous month.

Molecular Characterization of Penicillin-Resistant Streptococcus pneumoniae Isolates Causing Respiratory Disease in the United States

Abstract: Three hundred twenty-eight (328) penicillin-resistant Streptococcus pneumoniae isolates collected in 39 states of the United States between October, 1996, and March, 1997, from (mostly adult) patients with respiratory disease were characterized by microbiological, serological, and molecular fingerprinting techniques, including determination of chromosomal macrorestriction pattern with pulsed-field gel electrophoresis (PFGE) and hybridization with DNA probes specific for various antibiotic resistance genes. The overwhelming majority of the isolates were in five serogroups (23, 6, 19, 9, 14). All isolates had penicillin MIC values of at least 2 μg/ml, but the collection also included isolates with MIC values as high as 16 μg/ml. Virtually all isolates (96.6%) were resistant to trimethoprim/sulfamethoxazole (SXT) and many isolates were also resistant to chloramphenicol (43%), tetracycline (55%), and erythromycin (65%). Resistance to levofloxacin was extremely rare. The molecular fingerprinting metho...

Clinical characteristics and outcome of children with pneumonia attributable to penicillin-susceptible and penicillin-nonsusceptible Streptococcus pneumoniae.

Abstract: Objective. To compare the clinical characteristics, treatment, and outcome of pediatric patients with pneumonia attributable to isolates of Streptococcus pneumoniae that were either susceptible or nonsusceptible to penicillin. Design. Multicenter, retrospective study. Setting. Eight children9s hospitals in the United States. Participants. Two hundred fifty-four children with pneumococcal pneumonia identified from patients enrolled in the United States Pediatric Multicenter Pneumococcal Surveillance Study during the 3-year period from September 1, 1993 to August 31, 1996. Outcome Measures. Demographic and clinical variables including necessity for and duration of hospitalization, frequency of chest tube placement, antimicrobial therapy, susceptibility of isolates, and clinical outcome. Results. There were 257 episodes of pneumococcal pneumonia that occurred in 254 patients. Of the 257 isolates, 22 (9%) were intermediate and 14 (6%) were resistant to penicillin; 7 (3%) were intermediate to ceftriaxone and 5 (2%) were resistant to ceftriaxone. There were no differences noted in the clinical presentation of the patients with susceptible versus nonsusceptible isolates. Twenty-nine percent of the patients had a pleural effusion. The 189 (74%) hospitalized patients were more likely to have an underlying illness, multiple lung lobe involvement, and the presence of a pleural effusion than nonhospitalized patients. Fifty-two of 72 hospitalized patients with pleural effusions had a chest tube placed, and 27 subsequently underwent a decortication drainage procedure. Eighty percent of the patients treated as outpatients and 48% of the inpatients received a parenteral second or third generation cephalosporin followed by a course of an oral antimicrobial agent. Two hundred forty-eight of the patients (97.6%) had a good response to therapy. Six patients died; however, only 1 of the deaths was related to the pneumococcal infection. Conclusion. The clinical presentation and outcome of therapy did not differ significantly between patients with penicillin-susceptible versus those with nonsusceptible isolates ofS pneumoniae. Hospitalized patients were more likely to have underlying illnesses, multiple lobe involvement, and the presence of pleural effusions than patients who did not require hospitalization. In otherwise normal patients with pneumonia attributable to penicillin-resistant pneumococcal isolates, therapy with standard β-lactam agents is effective.

Antimicrobial susceptibility testing: general principles and contemporary practices.

Abstract: One of the most important tasks in the clinical microbiology laboratory is the performance of antimicrobial susceptibility tests on significant bacterial isolates. The goal of susceptibility testing is to predict the likely outcome of treating a patient's infection with a particular antimicrobial agent. Empirical therapy continues to be effective for some bacterial pathogens because resistance mechanisms have not yet been acquired or are still rare; examples include penicillin therapy for group A streptococcal infections, erythromycin for legionellosis, and penicillin for N. meningitidis infections in the United States. Susceptibility testing is useful and important for the common bacterial species that are not predictably susceptible to drugs of choice because of acquired resistance mechanisms (e.g., members of the Enterobacteriaceae, Pseudomonas species, Staphylococcus species, Enterococcus species, Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae). The two important and related functions of susceptibility testing are the detection of frank resistance and the quantitative measurement of susceptibility to antimicrobial agents with some species that may have direct therapeutic relevance, e.g., the magnitude of the penicillin and cephalosporin MICs for Streptococcus pneumoniae [1-3].

Susceptibilities of penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, compared with susceptibilities to 17 other agents.

Abstract: Susceptibility of 230 penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, was tested by agar dilution, and results were compared with those of erythromycin, azithromycin, clarithromycin, roxithromycin, rokitamycin, clindamycin, pristinamycin, ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline, chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. HMR 3647 was very active against all strains tested, with MICs at which 90% of the strains were inhibited (MIC90s) of 0.03 microg/ml for erythromycin-susceptible strains (MICs, or =1.0 microg/ml). All other macrolides yielded MIC90s of 0.03 to 0.25 and >64.0 microg/ml for erythromycin-susceptible and -resistant strains, respectively. The MICs of clindamycin for 51 of 100 (51%) erythromycin-resistant strains were < or =0.125 microg/ml. The MICs of pristinamycin for all strains were < or =1.0 microg/ml. The MIC90s of ciprofloxacin and sparfloxacin were 4.0 and 0.5 microg/ml, respectively, and were unaffected by penicillin or erythromycin susceptibility. Vancomycin and imipenem inhibited all strains at < or =1.0 microg/ml. The MICs of cefuroxime and cefotaxime rose with those of penicillin G. The MICs of trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol were variable but were generally higher in penicillin- and erythromycin-resistant strains. HMR 3647 had the best kill kinetics of all macrolides tested against 11 erythromycin-susceptible and -resistant strains, with uniform bactericidal activity (99.9% killing) after 24 h at two times the MIC and 99% killing of all strains at two times the MIC after 12 h for all strains. Pristinamycin showed more rapid killing at 2 to 6 h, with 99.9% killing of 10 of 11 strains after 24 h at two times the MIC. Other macrolides showed significant activity, relative to the MIC, against erythromycin-susceptible strains only.

Why Have Group A Streptococci Remained Susceptible to Penicillin? Report on a Symposium

Abstract: In spite of 50 years of extensive use of penicillin, group A streptococci remain exquisitely susceptible to this antibiotic. This observation that continuing susceptibility has occurred despite the development of resistance to other antimicrobial agents prompted a day-long meeting at Rockefeller University (New York) in October 1996. Among the most likely explanations for this remarkable state of continued susceptibility to penicillin are that beta-lactamase may not be expressed or may be toxic to the organism and/or that low-affinity penicillin-binding proteins either are not expressed or render organisms nonviable. Other potential explanations are that circumstances favorable for the development of resistance have not yet occurred and/or that there are inefficient mechanisms for or barriers to genetic transfer. Recommended future actions include (1) additional laboratory investigations of gene transfer, penicillin-binding proteins, virulence factors, and homeologous recombination and mismatch repair; (2) increased surveillance for the development of penicillin resistance; (3) application of bioinformatics to analyze streptococcal genome sequences; and (4) development of vaccines and novel antimicrobial agents. Thus far the susceptibility of group A streptococci to penicillin has not been a major clinical or epidemiological problem. A similar observation, however, could have been made decades ago about Streptococcus pneumoniae. It is therefore vital for the scientific community to closely examine why penicillin has remained uniformly highly active against group A streptococci in order to maintain this desirable state.

Antimicrobial susceptibility of viridans group streptococci in Taiwan with an emphasis on the high rates of resistance to penicillin and macrolides in Streptococcus oralis.

Abstract: The in-vitro susceptibilities of 13 antimicrobial agents were determined for 207 isolates of viridans group streptococci recovered from patients with significant infections in Taiwan during 1995 and 1997. Variable degrees of susceptibility existed among nine species. High-level penicillin resistance (MIC > or = 4.0 mg/L) was found most frequently in Streptococcus oralis (35%), followed by Streptococcus mitis (20%) and Streptococcus salivarius (8%). However, S. salivarius showed the lowest rate of susceptibility to penicillin (50%). Macrolide resistance also occurred most frequently in S. oralis isolates (55%) but in none of Streptococcus mutans. Penicillin and macrolides tended to be less active against isolates recovered from non-invasive sites than against those isolated from invasive sites. Imipenem was the most active beta-lactam against penicillin-resistant isolates. Ofloxacin, vancomycin and teicoplanin showed good in-vitro activity against all isolates, with MIC90s of 2, 1 and 0.25 mg/L, respectively. None of these isolates displayed high-level resistance to gentamicin and most isolates were susceptible to chloramphenicol. These results indicate the species-related variability of susceptibility, especially to penicillin, macrolides and tetracycline. In addition to S. mitis, S. oralis also displayed high rates of resistance to penicillin and macrolides. The difference in susceptibilities between species of viridans streptococci indicates the importance of accurate identification and the need for continuing surveillance of antimicrobial resistance.

Alterations in PBP 1A Essential for High-Level Penicillin Resistance in Streptococcus pneumoniae

Abstract: High-level penicillin resistance in pneumococci is due to alterations in penicillin-binding proteins (PBPs) 2X, 2B, and 1A. We have sequenced the penicillin-binding domain of PBP 1A from penicillin-resistant South African pneumococcal isolates and have identified amino acid substitutions which are common to all the resistant isolates analyzed. Site-directed mutagenesis was then used to determine whether particular amino acid substitutions at specific positions in PBP 1A mediate penicillin resistance. PCR was used to isolate PBP 2X, 2B, and 1A genes from clinical isolate 8303 (penicillin MIC, 4 μg/ml). These wild-type PBP genes were cloned into pGEM-3Zf and were used as the transforming DNA. Susceptible strain R6 (MIC, 0.015 μg/ml) was first transformed with PBP 2X and 2B DNA, resulting in PBP 2X/2B-R6 transformants for which MICs were 0.25 μg/ml. When further transformed with PBP 1A DNA, 2X/2B/1A-R6 transformants for which MICs were 1.5 μg/ml were obtained. Site-directed mutagenesis of the PBP 1A gene from isolate 8303 was then used to reverse particular amino acid substitutions, followed by transformation of PBP 2X/2B-R6 transformants with the mutagenized PBP 1A DNA. For PBP 2X/2B/1A-R6 transformants, the introduction of the reversal of Thr-371 by Ser or Ala in PBP 1A decreased the MIC from 1.5 to 0.5 μg/ml, whereas the reversal of four consecutive amino acid substitutions (Thr-574 by Asn, Ser-575 by Thr, Gln-576 by Gly, and Phe-577 by Tyr) decreased the MIC from 1.5 to 0.375 μg/ml. These data reveal that amino acid residue 371 and residues 574 to 577 of PBP 1A are important positions in PBP 1A with respect to the interaction with penicillin and the development of resistance.

Antimicrobial Susceptibilities of Group B Streptococci Isolated between 1992 and 1996 from Patients with Bacteremia or Meningitis

Abstract: In vitro testing of 229 group B streptococcal isolates from a variety of patients with invasive infections indicated uniform penicillin G susceptibility. However, 17 (7.4%) isolates were resistant to erythromycin and 8 (3.4%) were resistant to clindamycin. These results support the continued use of penicillin G as the drug of choice for the treatment and prevention of group B streptococcal disease.

Forty years of beta-lactam research.

Abstract: From the Editor-in-Chief: For more than 40 years the author has been involved in research in the field of β-lactam antibiotics. Much of this work was concerned with the development of the semisynthetic penicillins, following the isolation of the penicillin nucleus, 6-aminopenicillanic acid. This work resulted in the introduction of a number of important antibiotics including methicillin, cloxacillin, flucloxacillin, ampicillin, amoxycillin, carbenicillin and ticarcillin. Many of these compounds also provided the incentive or the basis for studies of a more fundamental nature in cell biology and antibacterial chemotherapy. The following is the author's personal account of some of the studies in the β-lactam field in which he has been involved.

Prevalence and antimicrobial susceptibility of staphylococci isolated from the skin surface of clinically normal cats

Abstract: Samples were collected from 148 adult cats, processed for isolation of Staphylococcus species and tested for susceptibility to penicillin G, gentamicin, oxacillin, amoxycillin, ampicillin, cephalexin and rifampin. Methicillin resistance was also determined. Ninety-eight isolates were obtained (66% of samples). Coagulase-negative species were most common, and the most frequently isolated species (37 samples) was Staph. felis. Other coagulase-negative species, such as Staph. simulans, Staph. epidermidis and Staph. saprophyticus were also isolated. Coagulase-positive species were obtained from 40 cats; the most frequent was Staph. intermedius (26 samples), followed by Staph. aureus (14 samples). Resistance to antibiotics was frequently observed, with 58.2% of the isolates showing resistance to at least one drug. Resistance to Penicillin G was observed in 49 of the 98 isolates (50%), 22 samples were resistant to oxacillin (22.4%) and 12 to rifampin (12.2%). Resistance to amoxycillin and ampicillin was very similar to that observed to Penicillin G. Gentamicin was the most active antimicrobial agent. Three MRSA (methicillin-resistant Staphylococcus aureus) were isolated, which represents 21.4% of the isolates of that species. Nineteen MRS (methicillin resistant staphylococci) were also observed, distributed among Staph. intermedius (eight), Staph. simulans (six) and Staph. felis (five) isolates. The role of these micro-organisms on the skin of cats is discussed.

Extremely High Prevalence of Nasopharyngeal Carriage of Penicillin-Resistant Streptococcus pneumoniae among Children in Kaohsiung, Taiwan

Abstract: Resistance (intermediate and high) to penicillin among Streptococcus pneumoniae strains is an emerging problem worldwide. From 1995 to 1997, isolates of S. pneumoniae not susceptible to penicillin were seen with increasing frequency from blood, cerebrospinal fluid, pleural fluid, and middle ear fluid from pediatric patients at the Veterans General Hospital-Kaohsiung. To determine the prevalence of carriage of these penicillin-nonsusceptible S. pneumoniae isolates, we obtained nasopharyngeal swab specimens from 2,905 children (ages, 2 months to 7 years) attending day-care centers or kindergartens or seen in our outpatient clinic. S. pneumoniae was isolated from 611 children, and 584 strains were available for analysis. The oxacillin disc test was used as a screening test to evaluate penicillin susceptibility. The MICs of 11 antibiotics (penicillin, cefaclor, cefuroxime, ceftriaxone, cefotaxime, imipenem, chloramphenicol, clarithromycin, rifampin, vancomycin, and teicoplanin) were determined by the E-test. Only 169 (29%) of the strains were susceptible to penicillin; 175 (30%) strains were intermediately resistant and 240 (41%) were highly resistant. The isolates also demonstrated high rates of resistance to other β-lactams (46% were resistant to cefaclor, 45% were resistant to cefuroxime, 45% were resistant to ceftriaxone, 31% were resistant to cefotaxime, and 46% were resistant to imipenem). The rate of resistance to macrolide antimicrobial agents was strikingly high; 95% of the isolates were not susceptible to clarithromycin. However, 97% were susceptible to rifampin and 100% were susceptible to the two glycopeptides (vancomycin and teicoplanin). While reports of penicillin-resistant S. pneumoniae increased worldwide through the 1980s, the high prevalence (71%) of resistance reported here is astonishing. Surveillance of nasopharyngeal swab specimen cultures may provide useful information on the prevalence of nonsusceptible strains causing invasive disease. Such information could be used to guide therapy of pneumococcal infections.

Studies of the continuing susceptibility of group A streptococcal strains to penicillin during eight decades.

Abstract: Background.In view of the widespread use of penicillin for >50 years for the treatment of group A streptococcal infections, we examined the question of whether there has been a change in susceptibility to penicillin in group A streptococcal strains collected during a span of 80 years (1917 to 19

Antimicrobial resistance of bacteria isolated from slaughtered and retail chickens in South Africa

Abstract: Animal feed is increasingly being supplemented with antibiotics to decrease the risk of epidemics in animal husbandry. This practice could lead to the selection for antibiotic resistant micro-organisms. The aim of this study was to determine the level of antibiotic resistant bacteria present on retail and abattoir chicken. Staphylococci, Enterobacteriaceae, Salmonella and isolates from total aerobic plate count were tested for resistance to vancomycin, streptomycin, methicillin, tetracycline and gentamicin using the disc diffusion susceptibility test; resistance to penicillin was determined using oxacillin. Results from the antibiotic code profile indicated that many of the bacterial strains were displaying multiple antibiotic resistance (MAR). A larger proportion of resistance to most antibiotics, except for vancomycin, was displayed by the abattoir samples, therefore suggesting that the incidence of MAR pathogenic bacteria was also higher in the abattoir samples. This resistance spectrum of abattoir samples is a result of farmers adding low doses of antibiotics to livestock feed to improve feeding efficiency so that the animals need less food to reach marketable weight. The lower incidence of MAR pathogenic bacteria in the retail samples is a result of resistance genes being lost due to lack of selective pressure, or to the fact that the resistant flora are being replaced by more sensitive flora during processing. The use of subtherapeutic levels of antibiotics for prophylaxis and as growth promoters remains a concern as the laws of evolution dictate that microbes will eventually develop resistance to practically any antibiotic. Selective pressure exerted by widespread antimicrobial use is therefore the driving force in the development of antibiotic resistance. This study indicated that a large proportion of the bacterial flora on fresh chicken is resistant to a variety of antibiotics, and that resultant food-related infections will be more difficult to treat.

Efficacy of parenteral administration of three antimicrobial agents in treatment of clinical mastitis in lactating cows: 487 cases (1989-1995).

Abstract: OBJECTIVE To evaluate the efficacy of parenteral administration of procaine penicillin G, spiramycin, or enrofloxacin in the treatment of clinical mastitis in lactating cows DESIGN Noncontrolled, clinical retrospective study ANIMALS 487 cows with mastitis involving 543 quarters PROCEDURE Clinical signs, histories, and results of bacteriologic examination, somatic cell count, and N-acetyl-beta-D-glucosaminidase activity of milk samples taken before and 3 to 4 weeks after treatment were retrieved from hospital records Cows treated parenterally with procaine penicillin G, spiramycin, or enrofloxacin for 3 to 5 days were included Supportive treatment alone was given to 35 cows infected with Escherichia coli Factors possibly affecting outcome were analyzed, using ANOVA, correlation analyses, and the Mann-Whitney test chi 2 Test was used to compare bacteriologic cure rates RESULTS Bacteriologic cure rates for mastitis caused by Staphylococcus aureus, coagulase-negative staphylococci, and streptococci were 34, 76, and 65%, respectively Cure rates in cows in their first lactation and infected with S aureus and coagulase-negative staphylococci were significantly higher than those for older cows In cows with mastitis caused by E coli, the cure rate was 74% for those treated with penicillin G and 71% for those not treated with antimicrobials High N-acetyl-beta-D-glucosaminidase activity in milk samples obtained at initial examination indicated a poor outcome in S aureus and streptococcal mastitis Cows infected in the early lactation period had more severe inflammatory responses and clinical signs if infected with coagulase-negative staphylococci and coliforms CLINICAL IMPLICATIONS 3 to 5 days of treatment with parenterally administered penicillin G for clinical mastitis caused by penicillin-susceptible S aureus strains is efficacious in young cows Parenteral administration of spiramycin or enrofloxacin does not give satisfactory results in mastitis caused by penicillin-resistant S aureus Use of antimicrobials in the treatment of mastitis caused by coliform bacteria is questionable

Influence of recent antibiotic therapy on antimicrobial resistance of Streptococcus pneumoniae in children with acute otitis media in Spain.

Abstract: Background Despite the high prevalence of penicillin resistance among Streptococcus pneumoniae strains in Spain (40 to 60% with MIC > or = 0.1 microg/ml), the data on acute otitis media (AOM) isolates are scarce. We conducted a prospective, longitudinal study to determine the rates of antimicrobial resistance of S. pneumoniae isolates from children with AOM in our country and to analyze the effect of previous antibiotic therapy on these rates. Methods Tympanocentesis was performed on 169 children diagnosed with AOM (age range, 1 month to 14 years). Two groups were considered: Group A, 113 patients with non-antibiotic-treated AOM, subdivided into Group A1 (collected from 1989 to 1992) and Group A2 (1992 to 1996); Group B, 56 patients from the period 1992 to 1996, with AOM clinical failure, defined as worsening or persistent symptoms after at least 2 days of appropriate antibiotic therapy. Amoxicillin-clavulanate was the most frequent antibiotic used (68%), followed by azithromycin (21%), cefaclor and cefixime (11%). Results A total of 63 S. pneumoniae isolates were recovered, 42 in Group A and 21 in Group B. Resistance to penicillin (MIC > or = 0.1 microg/ml) was found in 38% of strains in Group A (32% in A1 and 50% in A2), but in Group B the rate of resistance reached 90% (P = 0.0002). Erythromycin resistance was also increased from 35% (Group A2) to 62% (Group B), and trimethoprim-sulfamethoxazole resistance rose from 64% to 81%. Conclusions Resistance to penicillin among S. pneumoniae AOM isolates is frequent and is increasing in Spain. After failure of standard antibiotic therapy, the rates of penicillin resistance reached 90% of the isolates.

Group A beta-hemolytic streptococcal infections.

Abstract: GABHS is the most common bacterial cause of tonsillopharyngitis, but this organism also produces acute otitis media; pneumonia; skin and soft-tissue infections; cardiovascular, musculoskeletal, and lymphatic infections; bacteremia; and meningitis. Most children and adolescents who develop a sore throat do not have GABHS as the cause; their infection is viral in etiology. Other bacterial pathogens produce sore throat infrequently (e.g., Chlamydia pneumoniae and Mycoplasma pneumoniae), and when they do, other concomitant clinical illness is present. Classic streptococcal tonsillopharyngitis has an acute onset; produces concurrent headache, stomach ache, and dysphagia; and upon examination is characterized by intense tonsillopharyngeal erythema, yellow exudate, and tender/enlarged anterior cervical glands. Unfortunately only about 20% to 30% of patients present with classic disease. Physicians overdiagnose streptococcal tonsillopharyngitis by a wide margin, which almost always leads to unnecessary treatment with antibiotics. Accordingly, use of throat cultures and/or rapid GABHS detection tests in the office is strongly advocated. Their use has been shown to be cost-effective and to reduce antibiotic overprescribing substantially. Penicillin currently is recommended by the American Academy of Pediatrics and American Heart Association as first-line therapy for GABHS infections; erythromycin is recommended for those allergic to penicillin. Virtually all patients improve clinically with penicillin and other antibiotics. However, penicillin treatment failures do occur, especially in tonsillopharyngitis in which 5% to 35% of patients do not experience bacteriologic eradication. Penicillin treatment failures are more common among patients who have been treated recently with the drug. Cephalosporins or azithromycin are preferred following penicillin treatment failures in selected patients as first-line therapy, based on a history of penicillin failures or lack of compliance and for impetigo. GABHS remain exquisitely sensitive to penicillin in vitro. There are several explanations for penicillin treatment failures, but the possibility of copathogen co-colonization in vivo has received the most attention. Treatment duration with penicillin should be 10 days to optimize cure in GABHS infections. A 5-day regimen is possible and approved by the United States Food and Drug Administration for cefpodoxime (a cephalosporin) and azithromycin (a macrolide). Prevention of rheumatic fever is the primary objective for antibiotic therapy of GABHS infections, but a reduction in contagion and faster clinical improvement also can be achieved. Development of streptococcal toxic shock syndrome and necrotizing fasciitis ("flesh-eating bacteria") are rising concerns. The portal of entry for these invasive GABHS strains is far more often skin and soft tissue than the tonsillopharynx.

Resistance to antibiotics used in dermatological practice.

Abstract: The increased prevalence of bacterial resistance is one of the major problems of medicine today. Antibiotic resistance can be defined as the situation where the minimal inhibitory concentration is greater than the concentration obtainable in vivo. Resistance genes are easily transferred among bacteria, especially bacteria on skin and mucous membranes. In dermatological patients the most important resistance problems are found among staphylococci, Propionibacterium acnes and, to some extent, streptococci. Staphylococcus aureus strains have developed worldwide resistance to penicillin due to betalactamase production in > 90% of cases, and methicillin resistance is now a major problem with resistance levels of > 50% in certain areas of the world. These resistant strains are often multiresistant, and include resistance to erythromycin and tetracycline, with resistance to quinolone developing rapidly. Group A streptococci are still susceptible to penicillin, but increasing problems with erythromycin and tetracycline have been reported. After treatment with both systemic and oral antibiotics, P. acnes develops resistance in more than 50% of cases, and it is estimated that one in four acne patients harbours strains resistant to tetracycline, erythromycin, and clindamycin. To limit the development of antibiotic resistance, it is necessary to establish an antibiotic policy (prescription rules, reimbursement strategy, development of both national and local guidelines, and limitations on non-medical use). Clinicians also need access to rapid diagnostic methods, including resistance testing. This may provide further data for surveillance systems, reporting both antibiotic consumption and resistance levels. The involvement of clinical doctors in teaching and research in this area is probably the most important aspect, along with their involvement in the formulation of national and local guidelines. In the future we may consider it more important to ensure that future patients can be offered antibiotic treatment, rather than focusing on the patient presenting today.

Community acquired infections and bacterial resistance

Abstract: In this paper we review the problems of antibiotic resistance in community acquired infections. We discuss pathogens that have a large impact on morbidity and mortality in the community such as Streptococcus pneumoniae , Streptococcus pyogenes , Neisseria meningitidis , the enteric pathogens Salmonella spp and Campylobacter spp, and the urinary tract pathogen Escherichia coli . #### Summary points The frequency of resistance to antibiotics among community acquired pathogens and the number of drugs to which they are resistant is increasing Resistance to antimicrobial drugs has been clearly linked to consumption of antibiotics The boundaries between community and hospital environments are becoming more blurred and this may have consequences for the development of resistance to antimicrobial drugs Strategies to limit the spread of resistant strains should include encouraging the judicious use of antimicrobial agents Guidelines should be based on results derived from well designed surveillance studies Infection with S pneumoniae is the biggest cause of potentially life threatening, community acquired diseases such as meningitis and pneumonia. It is also the leading bacterial cause of otitis media and sinusitis. However, this pathogen has evolved to reach unexpected levels of resistance to antibiotics. Before the early 1990s most pneumococci isolated in the European Union and the United States were susceptible to penicillin, with minimum inhibitory concentrations of <0.1 mg/l1; this concentration of penicillin killed these organisms rapidly. Since then, resistance to penicillin has increased substantially in certain European countries and in the United States. 2 3 Unfortunately, different authors have used different inhibitory concentrations to define penicillin resistance. However, susceptibility to penicillin is defined by many authors as a minimum inhibitory concentration of <0.1 mg/l; penicillin resistance is classed as intermediate when the minimum inhibitory concentration for S pneumoniae is 0.1-1.0 mg/l, and high when the minimum inhibitory concentration is 2.0 mg/l. Treatment regimens have been proposed …