Penicillin Minimum Inhibitory Concentration Research Articles

Low incidence of antibiotic resistance among invasive and nasopharyngeal isolates of Streptococcus pneumoniae from children in rural Philippines between 1994 and 2000

The purpose of this study was to determine the prevalence of acquired antimicrobial resistance in Streptococcus pneumoniae isolated from nasopharyngeal swabs and blood and cerebrospinal fluid (CSF) specimens of 3,028 children hospitalized with signs or symptoms of pneumonia, sepsis, or meningitis in rural Philippines between 1994 and 2000. Pneumococci were identified using standard methods, serotyped, and their susceptibility to oxacillin, erythromycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole was determined using the disk diffusion method. Penicillin minimum inhibitory concentrations (MICs) of the oxacillin-resistant isolates were further tested. The clonality of the penicillin-nonsusceptible (PNSP) isolates was analyzed using pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Altogether 1,048 isolates were analyzed, of which 35 were invasive and 1,013 nasopharyngeal isolates. None was resistant, but 22 (2.1%) were intermediately resistant to penicillin, 4 (0.2%) were resistant to chloramphenicol, 3 (0.2%) to erythromycin, 39 (3.7%) to tetracycline, and 4 (0.2%) to trimethoprim/sulfamethoxazole. Twelve of the 22 PNSP isolates were of serotype 14 and of sequence type 63. These included the two invasive PNSP isolates. PFGE profiling further identified three separate clusters among the sequence of type 63, serotype 14 (ST63(14)) isolates. Antimicrobial resistance in both invasive and nasopharyngeal pneumococcal pediatric isolates in rural Philippines is rare. In spite of this remote setting, the PNSP isolates of the serotype 14 clusters were of ST63 type, which has been described previously on other continents.

European surveillance study on antimicrobial susceptibility of Gram-positive anaerobic cocci

Gram-positive anaerobic cocci (GPAC) are a heterogeneous group of microorganisms frequently isolated from local and systemic infections. In this study, the antimicrobial susceptibilities of clinical strains isolated in 10 European countries were investigated. After identification of 299 GPAC to species level, the minimum inhibitory concentrations of penicillin, imipenem, clindamycin, metronidazole, vancomycin and linezolid were determined by the agar dilution method according to the Clinical and Laboratory Standards Institute. The majority of isolates were identified as Finegoldia magna and Parvimonas micra (formerly Peptostreptococcus micros), isolated from skin and soft tissue infections. All isolates were susceptible to imipenem, metronidazole, vancomycin and linezolid. Twenty-one isolates (7%) were resistant to penicillin ( n = 13) and/or to clindamycin ( n = 12). Four isolates were resistant to both agents. The majority of resistant isolates were identified as F. magna and originated from blood, abscesses and soft tissue infections.

Effect of Anti-Microbial Fiber and its Interaction with Penicillin G on Opportunistic Skin Micro-Flora

Objective The standard of hygiene in daily life and hospitals can be increased by the use of new antimicrobial fibers, which diminish the danger of pathogenic bacteria. In this study, the antimicrobial effect of special fibers on some staphylococcus isolates was investigated. Materials and Methods The antimicrobial effect of special type of fibers produced in Isfahan Poly Acryl Plant on three species of Staphylococcus aureus, epidermidis and lugdunensis isolated from 96 samples of hand and foot skin micro-flora was studied. The sensitivity of strains regarding resistant strains, to various antibiotics and beta-lactamase enzyme production was studied. The most resistance to antibiotics and beta-lactamase producer were chosen. Using the cup plate method, the inhibiting effect of pure antimicrobial agent on these strains was proven. Next, using shake flask method the effect of antimicrobial fiber on these strains was studied. In order to compare the effect of the antimicrobial agent of the fiber with that of penicillin G, the minimal inhibitory concentration (MIC) of the fiber antimicrobial agent and of penicillin G was tested on the strains. The effect of the interaction of these two antimicrobial agents and their fractional inhibitory concentration (FIC) on the chosen strains was studied using checkerboard method. Results The results show a significant effect by antimicrobial fiber with 30%, 60% and 100% antimicrobial agent on Staphylococcus species after 24 hrs. Moreover despite the high level MIC of penicillin G on these bacteria (8-256 µg/ml), the MIC of the pure antimicrobial agent of fiber at a level of 10-4 µl/ml caused growth inhibition. The interaction of these two antibacterial agents on the chosen strains was evaluated as synergism. Conclusion According to this study the antimicrobial effect of the fiber on growth inhibition of common, resistant skin bacterial flora is positive and therefore may be used after other successful clinical trials.

Increasing penicillin and trimethoprim–sulfamethoxazole resistance in nasopharyngeal Streptococcus pneumoniae isolates from Guatemalan children, 2001–2006

We aimed to determine nasopharyngeal colonization rates and antibiotic resistance patterns of Streptococcus pneumoniae isolated from Guatemalan children, and to determine risk factors for colonization and antibiotic nonsusceptibility. Isolates were obtained from children aged 5 to 60 months attending public and private outpatient clinics and daycare centers during August 2001--June 2002 and outpatient clinics during November 2005--February 2006 in Guatemala City. Minimal inhibitory concentrations of penicillin, trimethoprim-sulfamethoxazole (TMS), cefotaxime, and erythromycin were determined using the E-test. The overall nasopharyngeal colonization rate for S. pneumoniae was 59.1%. From 2001/2 to 2005/6 TMS nonsusceptibility increased from 42.4% to 60.8% (p<0.05) in public clinics and from 51.4% to 84.0% (p=0.009) in private clinics, and penicillin nonsusceptibility increased from 1.5% to 33.3% in public clinics (p<0.001). Reported antibiotic use was not strictly associated with nonsusceptibility to that same antibiotic. Resistance to three or four antibiotics increased in public clinics from 2001/2 (0%) to 2005/6 (10.7%; p<0.001). Risk factors for nasopharyngeal colonization with penicillin- or TMS-nonsusceptible S. pneumoniae were low family income, daycare center attendance, and recent penicillin use. Increasing antibiotic nonsusceptibility rates in nasopharyngeal S. pneumoniae isolates from Guatemalan children reflect worldwide trends. Policies encouraging more judicious use of TMS should be considered.

Heteroresistance to penicillin in Streptococcus pneumoniae

Heteroresistance to beta-lactam antibiotics has been mainly described for staphylococci, for which it complicates diagnostic procedures and therapeutic success. This study investigated whether heteroresistance to penicillin exists in Streptococcus pneumoniae. Population analysis profile (PAP) showed the presence of subpopulations with higher penicillin resistance in four of nine clinical pneumococcal strains obtained from a local surveillance program (representing the multiresistant clones ST179, ST276, and ST344) and in seven of 16 reference strains (representing the international clones Spain(23F)-1, Spain(9V)-3, Spain(14)-5, Hungary(19A)-6, South Africa(19A)-13, Taiwan(23F)-15, and Finland(6B)-12). Heteroresistant strains had penicillin minimal inhibitory concentrations (MICs) (for the majority of cells) in the intermediate- to high-level range (0.19-2.0 mug/ml). PAP curves suggested the presence of subpopulations also for the highly penicillin-resistant strains Taiwan(19F)-14, Poland(23F)-16, CSR(19A)-11, and CSR(14)-10. PAP of bacterial subpopulations with higher penicillin resistance showed a shift toward higher penicillin-resistance levels, which reverted upon multiple passages on antibiotic-free media. Convergence to a homotypic resistance phenotype did not occur. Comparison of two strains of clone ST179 showed a correlation between the heteroresistant phenotype and a higher-penicillin MIC and a greater number of altered penicillin-binding proteins (PBP1a, -2b, and -2x), respectively. Therefore, heteroresistance to penicillin occurs in international multiresistant clones of S. pneumoniae. Pneumococci may use heteroresistance to penicillin as a tool during their evolution to high penicillin resistance, because it gives the bacteria an opportunity to explore growth in the presence of antibiotics before acquisition of resistance genes.

Native triple-valve endocarditis caused by penicillin-resistant Streptococcus sanguis

A 26-year-old man with known but untreated ventricular septal defect was admitted to the emergency ward with abdominal pain, fever and weight loss. Transthoracic echocardiography showed multiple vegetations on the anterior mitral leaflet, a mobile vegetation on the surface of the aortic noncoronary cusp and another on the tricuspid valve. His blood cultures grew Streptococcus sanguis with a penicillin minimum inhibitory concentration of 3 microg/ml. Physical examination, echocardiography, blood cultures, minimal inhibitory concentration detection. Multivalvular infective endocarditis caused by S. sanguis with a high penicillin resistance. A combination of intravenous vancomycin and gentamicin, followed by early surgery.

Direct and indirect antimicrobial effects and antioxidant activity of Cordia gilletii De Wild ( Boraginaceae)

Cordia gilletii De Wild (Boraginaceae) root bark is traditionally used in Democratic Republic of Congo (DRC) for the treatment of various disorders, including malaria, diarrhea, wounds and skin diseases; part of these activities may rely on antimicrobial and antioxidant properties. Successive extracts of root barks powder with n-hexane, dichloromethane, ethyl acetate, methanol and water were tested for antimicrobial activity, both direct and indirect (antibiotic resistance reversal), against 10 strains of bacteria and 1 strain of fungi by broth microdilution and agar diffusion methods. The eventual synergy between plant extracts and antibiotics was investigated by the determination of the fractional inhibitory concentration index (FIC index). The methanol extract showed direct antimicrobial activity against all tested microorganisms with minimum inhibitory concentrations (MIC) ranging between 125 and 1000 μg/ml, whereas the ethyl acetate and the dichloromethane extracts showed activity on four and three strains, respectively. 200 μg/ml of n-hexane and dichloromethane extracts decreased the MICs of penicillin and streptomycin 4–64-fold for methicillin-resistant Staphylococcus aureus. A synergistic effect was found between the methanol extract and tetracycline, whereas additive effects were observed for the other combinations tested. The methanol and dichloromethane extracts showed the greater antioxidant activity by scavenging the free radical DPPH with IC 50 values of 3.2 and 8.1 μg/ml, respectively. These results support the use of the plant in the treatment of infectious diseases and wounds; they warrant further studies as to the nature of active compounds.

Attenuation of penicillin resistance in a peptidoglycan O‐acetyl transferase mutant of Streptococcus pneumoniae

The level of penicillin resistance in clinical isolates of Streptococcus pneumoniae depends not only on the reduced affinity of penicillin binding proteins (PBPs) but also on the functioning of enzymes that modify the stem peptide structure of cell wall precursors. We used mariner mutagenesis in search of additional genetic determinants that may further attenuate the level of penicillin resistance in the bacteria. A mariner mutant of the highly penicillin-resistant S. pneumoniae strain Pen6 showed reduction of the penicillin minimum inhibitory concentration (MIC) from 6 to 0.75 microg ml(-1). Decrease in penicillin MIC was also observed upon introduction of the mutation (named provisionally adr, for attenuator of drug resistance) into representatives of major epidemic clones of penicillin-resistant pneumococci. Attenuation of resistance levels was specific for beta-lactams. The adr mutant has retained unchanged (low affinity) PBPs, unaltered murM gene and unchanged cell wall stem peptide composition, but the mutant became hypersensitive to exogenous lysozyme and complementation experiments showed that both phenotypes--reduced resistance and lysozyme sensitivity--were linked to the defective adr gene. DNA sequence comparison and chemical analysis of the cell wall identified adr as the structural gene of the pneumococcal peptidoglycan O-acetylase.

Pharmacokinetically Enhanced Amoxicillin/Clavulanate (2,000/125 mg) in Acute Bacterial Rhinosinusitis caused by Streptococcus Pneumoniae, Including Penicillin-Resistant Strains

We evaluated the efficacy of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2,000/125 mg) twice daily for the treatment of acute bacterial rhinosinusitis (ABRS) caused by Streptococcus pneumoniae, particularly penicillin-resistant S pneumoniae (PRSP; penicillin minimum inhibitory concentrations [MICs]: > or = 2 microg/ml. A total of 2,482 patients received study medication (safety population). Of these, 2,324 were clinically evaluable (efficacy population), and 1,156 of them had at least one pathogen isolated at screening (bacteriology population). S pneumoniae was isolated from 371 patients in the bacteriology population, including 37 with PRSP. Follow-up in the bacteriology population on days 17 through 28 revealed that amoxicillin/clavulanate therapy was successful in 345 of 371 patients with S pneumoniae infection (93.0%) and in 36 of 37patients with PRSP infection (97.3%), including 7 of 8 patients (87.5%) whose amoxicillin/clavulanic acid MICs were 4/2 microg/ml or higher. Pharmacokinetically enhanced amoxicillin/clavulanate was generally well tolerated, as only 2.2% of patients withdrew because of adverse events. This agent represents a valuable new therapeutic option for the empiric treatment of ABRS, particularly in areas where antimicrobial-resistant pathogens (including beta-lactamase-positive organisms) are prevalent, and for the treatment of patients who are at increased risk of infection with PRSP.

Characteristics of Baicalin Synergy with Penicillin or Notopterygium Ethanol Extracts Against Staphylococcus aureus

Baicalin facilitates the effectiveness of both penicillin and Notopterygium ethanol extracts (NEE) on Staphylococcus aureus. Two Staphylococcus aureus strains, ATCC29213 and 03-21 (a clinical isolate), were tested. When combined with 128 μg · mL −1 of baicalin, the minimum inhibitory concentration (MIC) of penicillin was reduced from 0.25 μg · mL −1 to 0.06 μg · mL −1, while that of NEE was reduced from 32 μg · mL −1 to 8 μg · mL −1 against ATCC29213. Against the 03-21 strain, the MIC of penicillin was reduced from 4 μg · mL −1 to 1 μg · mL −1, while that of NEE was reduced from 32 μg · mL −1 to 4 μg · mL −1. Viable number counting results show that combination of baicalin and penicillin acts on the killing mechanism, while the baicalin and NEE acts on the inhibition. These results show that baicalin acts as a synergistic ally with both penicillin and NEE but has different modes of action.

Efficacy/safety of amoxicillin/clavulanate in adults with bacterial rhinosinusitis

Purpose Acute bacterial rhinosinusitis (ABRS) is a common and uncomfortable condition, frequently caused by Streptococcus pneumoniae or Haemophilus influenzae. Antibacterial resistance among these and other common respiratory pathogens is now widespread and of concern. Pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg was developed to be effective against the common respiratory pathogens, including many resistant strains. Materials and methods This open-label, noncomparative study assessed the bacteriologic and clinical efficacy of amoxicillin/clavulanate 2000/125 mg in adult patients with ABRS. Requirements for study entry included a clinical diagnosis of ABRS supported by radiologic findings. In addition, sinus puncture for bacteriologic assessment was required at study entry. Results Overall, bacteriologic success (eradication or clinical evidence of eradication) at the follow-up visit (days 17–28) was achieved in 87.8% (722/822) of patients with 1 or more pathogen isolated at screening, in 93.2% (246/264) of patients with S pneumoniae, in 96.7% (29/30) of those with penicillin-resistant S pneumoniae (penicillin minimum inhibitory concentrations ≥2 μg/mL), and in 88.7% (110/124) of patients with β-lactamase–positive pathogens. Bacteriologic success was achieved against 6 of 7 S pneumoniae isolates with amoxicillin/clavulanic acid minimum inhibitory concentrations of 4/2 μg/mL or higher. Conclusions Amoxicillin/clavulanate 2000/125 mg was generally well tolerated. This new amoxicillin/clavulanate formulation provides a suitable option for empiric therapy for ABRS in adults.

Empiric First-line Antibiotic Treatment of Acute Otitis in the Era of the Heptavalent Pneumococcal Conjugate Vaccine

Our goal was to estimate the local prevalence of Streptococcus pneumoniae nonsusceptible to penicillin and amoxicillin after widespread use of the heptavalent pneumococcal vaccine and to revise community-specific recommendations for first-line antibiotic treatment of acute otitis media. We conducted serial prevalence surveys between 2000 and 2004 in the offices of community pediatricians in St Louis, Missouri. Study participants were children <7 years of age with acute upper respiratory infections. Children treated with an antibiotic in the past 4 weeks were excluded. S pneumoniae was isolated from nasopharyngeal swabs using standard techniques. Isolates with a penicillin minimum inhibitory concentration >2 microg/mL were considered to be S pneumoniae nonsusceptible to amoxicillin. There were 327 patients enrolled in the study. Between 2000 and 2004, vaccine coverage with > or =3 doses of heptavalent pneumococcal vaccine increased from 0% to 54%, but nasopharyngeal carriage of S pneumoniae was stable at 39%. The prevalence of S pneumoniae nonsusceptible to penicillin fell from 25% to 12% among patients, did not vary if <2 years of age, was reduced in children with > or =3 doses of heptavalent pneumococcal vaccine, and increased in child care attendees but reduced in attendees who had > or =3 doses of heptavalent pneumococcal vaccine. The prevalence of S pneumoniae nonsusceptible to amoxicillin in patients remained <5%. In our community, widespread use of heptavalent pneumococcal vaccine has reduced the prevalence of S pneumoniae nonsusceptible to penicillin, and the prevalence of S pneumoniae nonsusceptible to amoxicillin remains low (<5%). If antibiotic treatment is elected for children with uncomplicated acute otitis media, we recommend treatment with standard-dose amoxicillin (40-45 mg/kg per day) for children with > or =3 doses of heptavalent pneumococcal vaccine, regardless of age and child care status. High-dose amoxicillin should be used for children with <3 doses of heptavalent pneumococcal vaccine and those treated recently with an antibiotic.

Analysis of genetic markers of N. Gonorrhoeae resistance to β-lactam antibiotics

A complex method for detection of genetic markers of N. gonorrhoeae resistance to penicillin was developed. Mutations in penA and ponA genes were detected by minisequencing reaction with subsequent detection of reaction products by MALDI-TOF mass spectrometry. This approach was tested on 31 clinical strains of N. gonorrhoeae with minimum inhibitory concentration of penicillin from 0.03 to 8 microg/ml and higher. Mutations in penA and ponA genes in moderately resistant strains were shown (minimum inhibitory concentration up to 0.5 microg/ml) and mutations in penA, ponA, and penB genes in resistant strains (minimum inhibitory concentration more than 1.0 microg/ml). beta-Lactamase genes were detected in 4 strains with high resistance (minimum inhibitory concentration 4-8 and more microg/ml). Correlation between microbiological resistance and presence of respective mutations in the studied locuses was detected.

Antimicrobial resistance of Neisseria gonorrhoeae isolates from the Stuttgart and Heidelberg areas of southern Germany

The aim of the present study was to determine prospectively the antimicrobial susceptibility of Neisseria gonorrhoeae strains collected in southern Germany (Heidelberg and Stuttgart areas). Sixty-five N. gonorrhoeae strains, isolated between July 2004 and June 2005 from patients with uncomplicated gonorrhoea, were tested. Minimum inhibitory concentrations of penicillin, tetracycline, ciprofloxacin, azithromycin, spectinomycin, ceftriaxone, and cefixime were determined by the E test. All isolates were fully susceptible to ceftriaxone, cefixime, and spectinomycin. However, 21.5% (14/65), 29.2% (19/65), and 47.7% (31/65) of isolates were resistant to penicillin (>2.0 mg/l), tetracycline (>2.0 mg/l), and ciprofloxacin (>1.0 mg/l), respectively. Critical MICs of azithromycin (>1.0 mg/l, as defined by the Neisseria Reference Laboratory at the Centers for Disease Control) were found for five (7.7%) N. gonorrhoeae isolates. These data indicate a high prevalence of N. gonorrhoeae strains resistant to the antimicrobial agents currently used to treat gonococcal infections in the Heidelberg and Stuttgart areas. Even though the findings may not be representative of the general population in Germany, they nevertheless illustrate the need to establish an antimicrobial resistance surveillance system in order to control gonorrhoea effectively.

Use of Local Community Hospital Data for Surveillance of Antimicrobial Resistance

We sought to determine whether antimicrobial susceptibility data from a nonteaching community hospital could be used to detect statistically significant local increases in resistance among Streptococcus pneumoniae over a 5-year period. Minimum inhibitory concentrations (MICs) of penicillin and ceftriaxone from 1997-1998 were compared with those from 2000-2001. MICs of penicillin and ceftriaxone for organisms collected in a nonteaching community hospital in central Illinois were used for analysis. The hospital has 224 beds and a catchment area of approximately 40 miles. There were significant increases in MICs of penicillin and ceftriaxone between 1997-1998 and 2000-2001. The MIC of penicillin increased from 0.042 to 0.121 microg/mL (P = .001; 95% confidence interval, -1.713 to -0.388), and the MIC of ceftriaxone increased from 0.028 to 0.071 microg/mL (P = .005; 95% confidence interval, -1.353 to -0.188). There were no significant changes in the percentage of S. pneumoniae isolates that were resistant, intermediate, or susceptible to penicillin and ceftriaxone. MIC data from a community hospital can be used to detect local increases in the rate of resistance before antibiogram data show significant changes. This information is important for demonstrating to physicians the need to review local antibiotic use in the attempt to slow the development of resistant organisms in the community.

Efficacy of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2000/125 mg) in adults with community-acquired pneumonia caused by Streptococcus pneumoniae, including penicillin-resistant strains

Community-acquired pneumonia (CAP) is a common respiratory illness, frequently caused by Streptococcus pneumoniae. The prevalence of S. pneumoniae resistance to common antimicrobials has increased over recent years. A new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2000/125 mg) has been developed, designed to combat infections caused by S. pneumoniae, including penicillin-resistant (PRSP, penicillin minimum inhibitory concentrations (MICs) ≥2 mg/l) isolates, and those with elevated amoxicillin/clavulanic acid MICs, while maintaining coverage of β-lactamase-producing pathogens. A pooled efficacy analysis of four randomized (1:1) and one non-comparative clinical trials of amoxicillin/clavulanate, 2000/125 mg, given twice daily, was conducted in adult patients with CAP. Comparator agents were conventional amoxicillin/clavulanate formulations. At follow-up (days 16–39), efficacy (eradication of the initial pathogen or clinical cure in patients for whom no repeat culture was performed) in patients with S. pneumoniae infection was 92.3% (274/297) for amoxicillin/clavulanate, 2000/125 mg and 85.2% (46/54) for comparators ( P = 0.11). Twenty-four of 25 PRSP-infected patients receiving amoxicillin/clavulanate, 2000/125 mg were treated successfully. Both amoxicillin/clavulanate, 2000/125 mg and comparators were well tolerated, with few patients withdrawing from the studies.

Antibiotic Susceptibility Profile of Group B Streptococcus (Streptococcus agalactiae) at the Maternity Hospital, Kuwait

Objectives: This study was designed to determine the antibiotic susceptibility profile of clinical isolates of group B streptococcus(GBS, Streptococcus agalactiae) and to use the information for formulating appropriate intrapartum antibiotic policy for GBS carriage in pregnancy. Materials and Methods: A total of 1,166 clinical isolates (single isolates) of GBS obtained from vaginal/rectal samples of pregnant mothers seen at the Maternity Hospital, Kuwait were studied over a period of 43 months between May 1998 and December 2001. The isolates were identified by standard methods and their susceptibility to penicillin, ampicillin, cephalothin, clindamycin and erythromycin was determined by disk diffusion technique, minimal inhibitory concentration (MIC) using the Vitek automated sensitivity card system and E-test methods. Results: All the GBS isolates were fully susceptible to penicillin, ampicillin and cephalothin. Only 0.7 and 1.7% were resistant to erythromycin and clindamycin, respectively. Disk diffusion results interpreted by the standard interpretative criteria recommended by the National Committee on Clinical Laboratory Standards correlated well with Vitek results as well as the E-test for penicillin. The MIC of penicillin against all isolates ranged between 0.016 and 0.064 µg/ml. For the 6 months of 1998 and throughout 1999, the percentages of isolates susceptible at MICs of 0.016, 0.023, 0.032, 0.047 and 0.064 µg/ml were 6.5, 9.9, 31, 38.8 and 12%, respectively. The trend was similar in the subsequent years except that the percentage of isolates susceptible at MIC of 0.064 µg/ml increased to 26.6% in 2000, but went down to 4.4% in 2001. Conclusion: The trend in susceptibility of GBS to a variety of often used antibiotics for therapy and prophylaxis remained unchanged over nearly a 4-year period. The apparent increase in the number of isolates susceptible at higher MIC values of penicillin (0.047 and 0.064 µg/ml) in 2000 appears to be a bleb that cannot be explained by any event in the hospital for that year. Our data, based on susceptibility profiles, supports the use of penicillin or ampicillin for intrapartum chemoprophylaxis to prevent early-onset neonatal GBS infections.

Presence of a mutation in ponA1 of Neisseria gonorrhoeae in numerous clinical samples resistant to various β-lactams and other, structurally unrelated, antimicrobials

The number of resistant strains in patients with Neisseria gonorrhoeae urethritis has been increasing, making effective treatment difficult. Chromosomally mediated penicillin-resistant N. gonorrhoeae arise through alterations in penicillin-binding proteins (PBPs) and a decrease in outer membrane permeability. To understand the occurrence of penicillin resistance in patients with N. gonorrhoeae infection, we performed this study. In addition, we studied minimum inhibitory concentrations (MICs) of antimicrobials against N. gonorrhoeae strains. We measured the MICs of penicillin G, other beta-lactams, and other kinds of antimicrobials against 53 clinical N. gonorrhoeae isolates from male patients with urethritis in Hyogo and Osaka, Japan. The ponA genes, encoding PBP 1 of these isolates, were sequenced. Of the 53 isolates tested, 41 strains showed some resistance to penicillin G. A mutation in the ponA (ponA1) gene was identified in 46 isolates. There was a tendency that ponA mutant (ponA1) in N. gonorrhoeae led to higher antimicrobial MICs of beta-lactam antimicrobial agents (including penicillin) than those of non-ponA mutants. However, we found lower than expected MICs of penicillin and beta-lactams even in ponA mutants. Therefore, we consider that detailed investigations for the further understanding of the effect of other genes, such as penC (which is reported to be related to ponA1 in achieving high-level penicillin resistance) should be our next step.

Antimicrobial Resistance of Streptococcus pneumoniae Isolates of Outpatients in Germany, 1999–2000

Background: The aim of the study was to determine the prevalence of antimicrobial resistance among clinical isolates of Streptococcus pneumoniae during the winter of 1999–2000 in Germany. Methods: Pneumococcal isolates were prospectively collected by 14 different clinical microbiology laboratories. Minimal inhibitory concentrations of penicillin G, erythromycin A, clarithromycin, roxithromycin, azithromycin, clindamycin, levofloxacin and telithromycin were determined by the broth microdilution method. Results: Among 328 strains 4.6% were nonsusceptible to penicillin G (intermediate and resistant strains) and 9.5% were resistant to erythromycin A. Analysis of erythromycin-resistant strains for the underlying resistance determinants revealed that 12 (38.7%) belonged to the erm(B) and 19 (61.3%) to the mef(E) type of resistance. Among the macrolide-resistant strains, serotypes 19F (n = 9) and 14 (n = 8) were the predominant types. Conclusions: Macrolide resistance in Germany is of growing concern and mainly due to the high prevalence of pneumococci expressing the mef(E) type of resistance.

Developing community-specific recommendations for first-line treatment of acute otitis media: is high-dose amoxicillin necessary?

National recommendations are to use high-dose amoxicillin (80-90 mg/kg per day) to treat uncomplicated acute otitis media (AOM) in children who are at high risk for infection with nonsusceptible Streptococcus pneumoniae (NSSP). However, high-dose treatment may not be necessary if the local prevalence of NSSP is low. The objective of this study was to estimate the local prevalence of NSSP in children with acute upper respiratory illnesses and to develop community-specific recommendations for first-line empiric treatment of AOM. We conducted a cross-sectional prevalence study in the offices of 7 community pediatricians in St Louis, Missouri. S pneumoniae was isolated from nasopharyngeal swabs collected from children who were younger than 7 years and had AOM, nonspecific upper respiratory infection, cough, acute sinusitis, or pharyngitis. Children were excluded from the study when they had received an antibiotic in the previous 4-week period. Parents and providers completed a brief questionnaire to assess risk factors for carriage of NSSP. On the basis of National Clinical Chemistry Laboratory Standards, isolates with a penicillin minimum inhibitory concentration > or =0.12 microg/mL were considered to be nonsusceptible to penicillin (NSSP), and isolates with a penicillin minimum inhibitory concentration >2 microg/mL were categorized as nonsusceptible to standard-dose amoxicillin (35-45 mg/kg per day; NSSP-A). S pneumoniae was isolated from the nasopharynx of 85 (40%) of 212 study patients (95% confidence interval [CI]: 33%-47%); 41 (48%) of 85 isolates were NSSP (95% CI: 37%-59%), and 6 (7%) were NSSP-A (95% CI: 1.5%-13%). Among the 212 study patients, the prevalence of NSSP was 19% (95% CI: 14%-25%), and the prevalence of NSSP-A was 3% (95% CI: 0.6%-5%). Carriage of NSSP was increased in child care attendees compared with nonattendees (29% vs 14%; odds ratio: 2.6; 95% CI: 1.3-5.2). In our community, although the prevalence of NSSP among isolates of S pneumoniae identified from the nasopharynx of symptomatic children is high (48%), the probability of NSSP-A infection among symptomatic children is <5%. Our data support a recommendation to treat most children who have uncomplicated AOM with standard-dose amoxicillin. Children who attend child care or have recently received an antibiotic may require treatment with high-dose amoxicillin. Other communities may benefit from a similar assessment of the prevalence of NSSP and NSSP-A.