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Magnus Unemo - One of the best experts on this subject based on the ideXlab platform.

  • alanine 501 mutations in penicillin binding protein 2 from neisseria gonorrhoeae structure mechanism and effects on cephalosporin resistance and biological fitness
    Biochemistry, 2017
    Co-Authors: Joshua Tomberg, Magnus Unemo, Alena Fedarovich, Leah R Vincent, Ann E Jerse, Christopher Davies, R A Nicholas
    Abstract:

    Resistance of Neisseria gonorrhoeae to expanded-spectrum cephalosporins such as ceftriaxone and Cefixime has increased markedly in the past decade. The primary cephalosporin resistance determinant is a mutated penA gene, which encodes the essential peptidoglycan transpeptidase, penicillin-binding protein 2 (PBP2). Decreased susceptibility and resistance can be conferred by mosaic penA alleles containing upward of 60 amino acid changes relative to wild-type PBP2, or by nonmosaic alleles with relatively few mutations, the most important of which occurs at Ala501 located near the active site of PBP2. Recently, fully Cefixime- and ceftriaxone-resistant clinical isolates that harbored a mosaic penA allele with an A501P mutation were identified. To examine the potential of mutations at Ala501 to increase resistance to expanded-spectrum cephalosporins, we randomized codon 501 in a mosaic penA allele and transformed N. gonorrhoeae to increased Cefixime resistance. Interestingly, only five substitutions of Ala501 ...

  • is the tide turning again for cephalosporin resistance in neisseria gonorrhoeae in europe results from the 2013 european surveillance
    BMC Infectious Diseases, 2015
    Co-Authors: Michelle J Cole, Gianfranco Spiteri, Susanne Jacobsson, Rachel Pitt, Vlad Grigorjev, Magnus Unemo
    Abstract:

    Background: The emerging resistance to the extended-spectrum cephalosporins (ESCs) in Neisseria gonorrhoeae together with increasing incidence of gonorrhoea cases in many countries have been global public health concerns. However, in recent years the levels of ESC resistance have decreased in several regions worldwide. We describe the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) data from 2013, and compare them to corresponding data from 2009–2012. Methods: During 2013, N. gonorrhoeae isolates from 21 participating countries were examined. Antimicrobial susceptibility testing (Etest or agar dilution) was performed for Cefixime, ceftriaxone, ciprofloxacin, azithromycin, spectinomycin and gentamicin. Statistical analyses were performed to identify significant changes in resistance between years and to investigate associations between patients with resistant gonococcal isolates and collected epidemiological variables. Results: In total, 93 (4.7 %) of 1994 isolates displayed resistance to Cefixime, representing an increase compared to the 3.9 % detected in 2012 (p = 0.23). Cefixime resistance was detected in 13 (61.9 %) of the 21 countries. Cefixime resistance among men who have sex with men was only 1.2 %, compared to 5.6 % and 6.1 % in females and male heterosexuals, respectively. The univariate analysis confirmed that isolates resistant to Cefixime were more likely to be from females (OR 4.87, p < 0.01) or male heterosexuals (OR 5.32, p < 0.01). Seven (0.4 %) isolates displayed ceftriaxone resistance (in addition to Cefixime resistance) compared to three and 10 isolates in 2012 and 2011, respectively. All 93 isolates with Cefixime resistance were additionally resistant to ciprofloxacin and 16 (17.2 %) were also resistant to azithromycin. Among all tested isolates (n = 1994), the ciprofloxacin resistance level (52.9 %) was higher than in 2012 (50.1 %; p = 0.08), and azithromycin resistance (5.4 %) increased since 2012 (4.5 %; p = 0.16). Conclusions: In 2013, the ESC resistance was again slightly increasing in Europe. This emphasises the importance of implementing the actions outlined in the European and additional response plans, particularly activities strengthening the surveillance of antimicrobial resistance. Ceftriaxone combined with azithromycin remains a satisfactory option for the first-line treatment of gonorrhoea. However novel antimicrobials (new derivatives of previously developed antimicrobials or newly developed antimicrobials) for effective monotherapy or at least inclusion in new dual antimicrobial therapy regimens (combined with previously developed antimicrobials or novel antimicrobials) will likely be required.

  • molecular and structural analysis of mosaic variants of penicillin binding protein 2 conferring decreased susceptibility to expanded spectrum cephalosporins in neisseria gonorrhoeae role of epistatic mutations
    Biochemistry, 2010
    Co-Authors: Joshua Tomberg, Magnus Unemo, Christopher Davies, Robert A Nicholas
    Abstract:

    Mutations in penicillin-binding protein 2 (PBP 2) encoded by mosaic penA alleles are critical for intermediate resistance to the expanded-spectrum cephalosporins ceftriaxone and Cefixime in Neisseria gonorrhoeae. Three of the ~60 mutations present in mosaic alleles of penA, G545S, I312M, and V316T, have been reported to be responsible for increased resistance, especially to Cefixime (Takahata et al. 2006. Antimicrob Agents Chemother 50:3638-45). However, we observed that the minimum inhibitory concentrations (MICs) of penicillin, ceftriaxone, and Cefixime for a wild type strain (FA19) containing a penA gene with these three mutations increased only 1.5-, 1.5-, and 3.5-fold, respectively. In contrast, when these three mutations in a mosaic penA allele (penA35) were reverted back to wild type and the gene transformed into FA19, the MICs of the three antibiotics were reduced to near wild type levels. Thus, these three mutations display epistasis, in that their capacity to increase resistance to β-lactam antibiotics is dependent on the presence of other mutations in the mosaic alleles. We also identified an additional mutation, N512Y, that contributes to decreased susceptibility to expanded-spectrum cephalosporins. Finally, we investigated the effects of a mutation (A501V) currently found only in non-mosaic penA alleles on decreased susceptibility to ceftriaxone and Cefixime, under the expectation that this mutation may arise in mosaic alleles. Transfer of the mosaic penA35 allele containing an A501V mutation into FA6140, a chromosomally mediated penicillin-resistant isolate, increased the MICs of ceftriaxone (0.4 μg/ml) and Cefixime (1.2μg/ml) to levels above their respective breakpoints. The proposed structural mechanisms of these mutations are discussed in light of the recently published structure of PBP 2.

  • neisseria gonorrhoeae isolates with reduced susceptibility to Cefixime and ceftriaxone association with genetic polymorphisms in pena mtrr porb1b and pona
    Antimicrobial Agents and Chemotherapy, 2007
    Co-Authors: Robert Lindberg, Hans Fredlund, Robert A Nicholas, Magnus Unemo
    Abstract:

    The recent emergence and transmission of Neisseria gonorrhoeae isolates with reduced susceptibility to expanded-spectrum cephalosporins such as Cefixime and ceftriaxone have been reported. The aim of this study was to determine the correlation of different polymorphisms in the penA, mtrR, porB1b (penB), and ponA genes of N. gonorrhoeae with reduced susceptibility to Cefixime and ceftriaxone. Eighteen gonococcal isolates with reduced Cefixime and ceftriaxone susceptibility (Cefi) and two susceptible isolates were characterized using serovar determination, antibiograms, N. gonorrhoeae multiantigen sequence typing (NG-MAST), and sequencing of penA, mtrR, porB1b, and ponA alleles. For the Cefi isolates (n = 18), the MICs of Cefixime and ceftriaxone ranged between 0.032 to 0.38 μg/ml and 0.064 to 0.125 μg/ml, respectively. These isolates were assigned five different serovars and six divergent NG-MAST sequence types. Eleven isolates (61%) with higher MICs of Cefixime and ceftriaxone contained a nearly identical penA mosaic allele and previously described polymorphisms in mtrR (a single nucleotide [A] deletion in the promoter), penB (mutations in porB1b encoding loop 3 of PorB1b), and ponA (ponA1 polymorphism). The remaining seven Cefi isolates (39%), which had somewhat lower MICs of Cefixime and ceftriaxone, contained an aspartic acid insertion (Asp-345a) in PBP 2 in conjunction with alterations of 4 to 10 amino acid residues in the C-terminal region of the transpeptidase domain of penA. In conclusion, an unambiguous association between penA mosaic alleles, in conjunction with genetic polymorphisms in mtrR, porB1b, and ponA, and greater reduced susceptibility to Cefixime and ceftriaxone was identified.

  • neisseria gonorrhoeae isolates with reduced susceptibility to Cefixime and ceftriaxone association with genetic polymorphisms in pena mtrr porb1b and pona
    Antimicrobial Agents and Chemotherapy, 2007
    Co-Authors: Robert Lindberg, Hans Fredlund, Robert A Nicholas, Magnus Unemo
    Abstract:

    The recent emergence and transmission of Neisseria gonorrhoeae isolates with reduced susceptibility to expanded-spectrum cephalosporins such as Cefixime and ceftriaxone have been reported. The aim of this study was to determine the correlation of different polymorphisms in the penA, mtrR, porB1b (penB), and ponA genes of N. gonorrhoeae with reduced susceptibility to Cefixime and ceftriaxone. Eighteen gonococcal isolates with reduced Cefixime and ceftriaxone susceptibility (Cefi) and two susceptible isolates were characterized using serovar determination, antibiograms, N. gonorrhoeae multiantigen sequence typing (NG-MAST), and sequencing of penA, mtrR, porB1b, and ponA alleles. For the Cefi isolates (n = 18), the MICs of Cefixime and ceftriaxone ranged between 0.032 to 0.38 μg/ml and 0.064 to 0.125 μg/ml, respectively. These isolates were assigned five different serovars and six divergent NG-MAST sequence types. Eleven isolates (61%) with higher MICs of Cefixime and ceftriaxone contained a nearly identical penA mosaic allele and previously described polymorphisms in mtrR (a single nucleotide [A] deletion in the promoter), penB (mutations in porB1b encoding loop 3 of PorB1b), and ponA (ponA1 polymorphism). The remaining seven Cefi isolates (39%), which had somewhat lower MICs of Cefixime and ceftriaxone, contained an aspartic acid insertion (Asp-345a) in PBP 2 in conjunction with alterations of 4 to 10 amino acid residues in the C-terminal region of the transpeptidase domain of penA. In conclusion, an unambiguous association between penA mosaic alleles, in conjunction with genetic polymorphisms in mtrR, porB1b, and ponA, and greater reduced susceptibility to Cefixime and ceftriaxone was identified.

Robert A Nicholas - One of the best experts on this subject based on the ideXlab platform.

  • molecular and structural analysis of mosaic variants of penicillin binding protein 2 conferring decreased susceptibility to expanded spectrum cephalosporins in neisseria gonorrhoeae role of epistatic mutations
    Biochemistry, 2010
    Co-Authors: Joshua Tomberg, Magnus Unemo, Christopher Davies, Robert A Nicholas
    Abstract:

    Mutations in penicillin-binding protein 2 (PBP 2) encoded by mosaic penA alleles are critical for intermediate resistance to the expanded-spectrum cephalosporins ceftriaxone and Cefixime in Neisseria gonorrhoeae. Three of the ~60 mutations present in mosaic alleles of penA, G545S, I312M, and V316T, have been reported to be responsible for increased resistance, especially to Cefixime (Takahata et al. 2006. Antimicrob Agents Chemother 50:3638-45). However, we observed that the minimum inhibitory concentrations (MICs) of penicillin, ceftriaxone, and Cefixime for a wild type strain (FA19) containing a penA gene with these three mutations increased only 1.5-, 1.5-, and 3.5-fold, respectively. In contrast, when these three mutations in a mosaic penA allele (penA35) were reverted back to wild type and the gene transformed into FA19, the MICs of the three antibiotics were reduced to near wild type levels. Thus, these three mutations display epistasis, in that their capacity to increase resistance to β-lactam antibiotics is dependent on the presence of other mutations in the mosaic alleles. We also identified an additional mutation, N512Y, that contributes to decreased susceptibility to expanded-spectrum cephalosporins. Finally, we investigated the effects of a mutation (A501V) currently found only in non-mosaic penA alleles on decreased susceptibility to ceftriaxone and Cefixime, under the expectation that this mutation may arise in mosaic alleles. Transfer of the mosaic penA35 allele containing an A501V mutation into FA6140, a chromosomally mediated penicillin-resistant isolate, increased the MICs of ceftriaxone (0.4 μg/ml) and Cefixime (1.2μg/ml) to levels above their respective breakpoints. The proposed structural mechanisms of these mutations are discussed in light of the recently published structure of PBP 2.

  • neisseria gonorrhoeae isolates with reduced susceptibility to Cefixime and ceftriaxone association with genetic polymorphisms in pena mtrr porb1b and pona
    Antimicrobial Agents and Chemotherapy, 2007
    Co-Authors: Robert Lindberg, Hans Fredlund, Robert A Nicholas, Magnus Unemo
    Abstract:

    The recent emergence and transmission of Neisseria gonorrhoeae isolates with reduced susceptibility to expanded-spectrum cephalosporins such as Cefixime and ceftriaxone have been reported. The aim of this study was to determine the correlation of different polymorphisms in the penA, mtrR, porB1b (penB), and ponA genes of N. gonorrhoeae with reduced susceptibility to Cefixime and ceftriaxone. Eighteen gonococcal isolates with reduced Cefixime and ceftriaxone susceptibility (Cefi) and two susceptible isolates were characterized using serovar determination, antibiograms, N. gonorrhoeae multiantigen sequence typing (NG-MAST), and sequencing of penA, mtrR, porB1b, and ponA alleles. For the Cefi isolates (n = 18), the MICs of Cefixime and ceftriaxone ranged between 0.032 to 0.38 μg/ml and 0.064 to 0.125 μg/ml, respectively. These isolates were assigned five different serovars and six divergent NG-MAST sequence types. Eleven isolates (61%) with higher MICs of Cefixime and ceftriaxone contained a nearly identical penA mosaic allele and previously described polymorphisms in mtrR (a single nucleotide [A] deletion in the promoter), penB (mutations in porB1b encoding loop 3 of PorB1b), and ponA (ponA1 polymorphism). The remaining seven Cefi isolates (39%), which had somewhat lower MICs of Cefixime and ceftriaxone, contained an aspartic acid insertion (Asp-345a) in PBP 2 in conjunction with alterations of 4 to 10 amino acid residues in the C-terminal region of the transpeptidase domain of penA. In conclusion, an unambiguous association between penA mosaic alleles, in conjunction with genetic polymorphisms in mtrR, porB1b, and ponA, and greater reduced susceptibility to Cefixime and ceftriaxone was identified.

  • neisseria gonorrhoeae isolates with reduced susceptibility to Cefixime and ceftriaxone association with genetic polymorphisms in pena mtrr porb1b and pona
    Antimicrobial Agents and Chemotherapy, 2007
    Co-Authors: Robert Lindberg, Hans Fredlund, Robert A Nicholas, Magnus Unemo
    Abstract:

    The recent emergence and transmission of Neisseria gonorrhoeae isolates with reduced susceptibility to expanded-spectrum cephalosporins such as Cefixime and ceftriaxone have been reported. The aim of this study was to determine the correlation of different polymorphisms in the penA, mtrR, porB1b (penB), and ponA genes of N. gonorrhoeae with reduced susceptibility to Cefixime and ceftriaxone. Eighteen gonococcal isolates with reduced Cefixime and ceftriaxone susceptibility (Cefi) and two susceptible isolates were characterized using serovar determination, antibiograms, N. gonorrhoeae multiantigen sequence typing (NG-MAST), and sequencing of penA, mtrR, porB1b, and ponA alleles. For the Cefi isolates (n = 18), the MICs of Cefixime and ceftriaxone ranged between 0.032 to 0.38 μg/ml and 0.064 to 0.125 μg/ml, respectively. These isolates were assigned five different serovars and six divergent NG-MAST sequence types. Eleven isolates (61%) with higher MICs of Cefixime and ceftriaxone contained a nearly identical penA mosaic allele and previously described polymorphisms in mtrR (a single nucleotide [A] deletion in the promoter), penB (mutations in porB1b encoding loop 3 of PorB1b), and ponA (ponA1 polymorphism). The remaining seven Cefi isolates (39%), which had somewhat lower MICs of Cefixime and ceftriaxone, contained an aspartic acid insertion (Asp-345a) in PBP 2 in conjunction with alterations of 4 to 10 amino acid residues in the C-terminal region of the transpeptidase domain of penA. In conclusion, an unambiguous association between penA mosaic alleles, in conjunction with genetic polymorphisms in mtrR, porB1b, and ponA, and greater reduced susceptibility to Cefixime and ceftriaxone was identified.

Kristina Tröster - One of the best experts on this subject based on the ideXlab platform.

  • 5 day Cefixime therapy for bacterial pharyngitis and or tonsillitis comparison with 10 day penicillin v therapy
    Infection, 1995
    Co-Authors: Dieter Adam, Ulrike Hostalek, Kristina Tröster
    Abstract:

    In an open, controlled, randomized multicenter study, 160 children suffering from pharyngitis and/or tonsillitis were treated with either 8 mg Cefixime/kg body weight once daily for 5 days or 20,000 I.U. penicillin V/kg body weight t.i.d. for 10 days. One hundred fifty-one children were evaluable for clinical efficacy. In the Cefixime group, 65 (86.7%) children were cured, seven (9.3%) were significantly improved, one (1.3%) relapsed and in two (2.7%) therapy failed. Of the patients treated with penicillin V, 69 (90.8%) were cured, five (6.6%) improved, one (1.3%) relapsed and in one (1.3%) therapy failed. Elimination of initial pathogens occurred in 57 (82.6%) patients treated with Cefixime and in 60 (88.2%) treated with penicillin V. At 3 to 4 weeks after the end of treatment, six relapses were seen in the Cefixime group and eight in the penicillin V group. Mild-to-moderate adverse events that were possibly related to the medication were seen in four children treated with Cefixime and in five treated with penicillin V.

  • 5 day Cefixime therapy for bacterial pharyngitis and or tonsillitis comparison with 10 day penicillin v therapy Cefixime study group
    Infection, 1995
    Co-Authors: Dieter Adam, Ulrike Hostalek, Kristina Tröster
    Abstract:

    In an open, controlled, randomized multicenter study, 160 children suffering from pharyngitis and/or tonsillitis were treated with either 8 mg Cefixime/kg body weight once daily for 5 days or 20,000 I.U. penicillin V/kg body weight t.i.d. for 10 days. One hundred fifty-one children were evaluable for clinical efficacy. In the Cefixime group, 65 (86.7%) children were cured, seven (9.3%) were significantly improved, one (1.3%) relapsed and in two (2.7%) therapy failed. Of the patients treated with penicillin V, 69 (90.8%) were cured, five (6.6%) improved, one (1.3%) relapsed and in one (1.3%) therapy failed. Elimination of initial pathogens occurred in 57 (82.6%) patients treated with Cefixime and in 60 (88.2%) treated with penicillin V. At 3 to 4 weeks after the end of treatment, six relapses were seen in the Cefixime group and eight in the penicillin V group. Mild-to-moderate adverse events that were possible related to the medication were seen in four children treated with Cefixime and in five treated with penicillin V.

Robert Lindberg - One of the best experts on this subject based on the ideXlab platform.

  • neisseria gonorrhoeae isolates with reduced susceptibility to Cefixime and ceftriaxone association with genetic polymorphisms in pena mtrr porb1b and pona
    Antimicrobial Agents and Chemotherapy, 2007
    Co-Authors: Robert Lindberg, Hans Fredlund, Robert A Nicholas, Magnus Unemo
    Abstract:

    The recent emergence and transmission of Neisseria gonorrhoeae isolates with reduced susceptibility to expanded-spectrum cephalosporins such as Cefixime and ceftriaxone have been reported. The aim of this study was to determine the correlation of different polymorphisms in the penA, mtrR, porB1b (penB), and ponA genes of N. gonorrhoeae with reduced susceptibility to Cefixime and ceftriaxone. Eighteen gonococcal isolates with reduced Cefixime and ceftriaxone susceptibility (Cefi) and two susceptible isolates were characterized using serovar determination, antibiograms, N. gonorrhoeae multiantigen sequence typing (NG-MAST), and sequencing of penA, mtrR, porB1b, and ponA alleles. For the Cefi isolates (n = 18), the MICs of Cefixime and ceftriaxone ranged between 0.032 to 0.38 μg/ml and 0.064 to 0.125 μg/ml, respectively. These isolates were assigned five different serovars and six divergent NG-MAST sequence types. Eleven isolates (61%) with higher MICs of Cefixime and ceftriaxone contained a nearly identical penA mosaic allele and previously described polymorphisms in mtrR (a single nucleotide [A] deletion in the promoter), penB (mutations in porB1b encoding loop 3 of PorB1b), and ponA (ponA1 polymorphism). The remaining seven Cefi isolates (39%), which had somewhat lower MICs of Cefixime and ceftriaxone, contained an aspartic acid insertion (Asp-345a) in PBP 2 in conjunction with alterations of 4 to 10 amino acid residues in the C-terminal region of the transpeptidase domain of penA. In conclusion, an unambiguous association between penA mosaic alleles, in conjunction with genetic polymorphisms in mtrR, porB1b, and ponA, and greater reduced susceptibility to Cefixime and ceftriaxone was identified.

  • neisseria gonorrhoeae isolates with reduced susceptibility to Cefixime and ceftriaxone association with genetic polymorphisms in pena mtrr porb1b and pona
    Antimicrobial Agents and Chemotherapy, 2007
    Co-Authors: Robert Lindberg, Hans Fredlund, Robert A Nicholas, Magnus Unemo
    Abstract:

    The recent emergence and transmission of Neisseria gonorrhoeae isolates with reduced susceptibility to expanded-spectrum cephalosporins such as Cefixime and ceftriaxone have been reported. The aim of this study was to determine the correlation of different polymorphisms in the penA, mtrR, porB1b (penB), and ponA genes of N. gonorrhoeae with reduced susceptibility to Cefixime and ceftriaxone. Eighteen gonococcal isolates with reduced Cefixime and ceftriaxone susceptibility (Cefi) and two susceptible isolates were characterized using serovar determination, antibiograms, N. gonorrhoeae multiantigen sequence typing (NG-MAST), and sequencing of penA, mtrR, porB1b, and ponA alleles. For the Cefi isolates (n = 18), the MICs of Cefixime and ceftriaxone ranged between 0.032 to 0.38 μg/ml and 0.064 to 0.125 μg/ml, respectively. These isolates were assigned five different serovars and six divergent NG-MAST sequence types. Eleven isolates (61%) with higher MICs of Cefixime and ceftriaxone contained a nearly identical penA mosaic allele and previously described polymorphisms in mtrR (a single nucleotide [A] deletion in the promoter), penB (mutations in porB1b encoding loop 3 of PorB1b), and ponA (ponA1 polymorphism). The remaining seven Cefi isolates (39%), which had somewhat lower MICs of Cefixime and ceftriaxone, contained an aspartic acid insertion (Asp-345a) in PBP 2 in conjunction with alterations of 4 to 10 amino acid residues in the C-terminal region of the transpeptidase domain of penA. In conclusion, an unambiguous association between penA mosaic alleles, in conjunction with genetic polymorphisms in mtrR, porB1b, and ponA, and greater reduced susceptibility to Cefixime and ceftriaxone was identified.

Dieter Adam - One of the best experts on this subject based on the ideXlab platform.

  • 5 day Cefixime therapy for bacterial pharyngitis and or tonsillitis comparison with 10 day penicillin v therapy
    Infection, 1995
    Co-Authors: Dieter Adam, Ulrike Hostalek, Kristina Tröster
    Abstract:

    In an open, controlled, randomized multicenter study, 160 children suffering from pharyngitis and/or tonsillitis were treated with either 8 mg Cefixime/kg body weight once daily for 5 days or 20,000 I.U. penicillin V/kg body weight t.i.d. for 10 days. One hundred fifty-one children were evaluable for clinical efficacy. In the Cefixime group, 65 (86.7%) children were cured, seven (9.3%) were significantly improved, one (1.3%) relapsed and in two (2.7%) therapy failed. Of the patients treated with penicillin V, 69 (90.8%) were cured, five (6.6%) improved, one (1.3%) relapsed and in one (1.3%) therapy failed. Elimination of initial pathogens occurred in 57 (82.6%) patients treated with Cefixime and in 60 (88.2%) treated with penicillin V. At 3 to 4 weeks after the end of treatment, six relapses were seen in the Cefixime group and eight in the penicillin V group. Mild-to-moderate adverse events that were possibly related to the medication were seen in four children treated with Cefixime and in five treated with penicillin V.

  • 5 day Cefixime therapy for bacterial pharyngitis and or tonsillitis comparison with 10 day penicillin v therapy Cefixime study group
    Infection, 1995
    Co-Authors: Dieter Adam, Ulrike Hostalek, Kristina Tröster
    Abstract:

    In an open, controlled, randomized multicenter study, 160 children suffering from pharyngitis and/or tonsillitis were treated with either 8 mg Cefixime/kg body weight once daily for 5 days or 20,000 I.U. penicillin V/kg body weight t.i.d. for 10 days. One hundred fifty-one children were evaluable for clinical efficacy. In the Cefixime group, 65 (86.7%) children were cured, seven (9.3%) were significantly improved, one (1.3%) relapsed and in two (2.7%) therapy failed. Of the patients treated with penicillin V, 69 (90.8%) were cured, five (6.6%) improved, one (1.3%) relapsed and in one (1.3%) therapy failed. Elimination of initial pathogens occurred in 57 (82.6%) patients treated with Cefixime and in 60 (88.2%) treated with penicillin V. At 3 to 4 weeks after the end of treatment, six relapses were seen in the Cefixime group and eight in the penicillin V group. Mild-to-moderate adverse events that were possible related to the medication were seen in four children treated with Cefixime and in five treated with penicillin V.