Streptococcal Pharyngitis Therapy: Comparison of Clindamycin Palmitate and Potassium Phenoxymethyl Penicillin

Stillerman, Maxwell; Isenberg, Henry D.; Facklam, Richard R.

doi:10.1128/aac.4.5.514

Cited by 49 publications

(23 citation statements)

References 17 publications

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“…Clindamycin's intrinsic resistance to the enzyme ␤-lactamase enabled it to eliminate BLPO such as S. aureus, pigmented Prevotella species, and Fusobacterium species. This feature explained its efficacy in the treatment of acute (15) and recurrent (2) GABHS pharyngotonsillitis and eradication of the carrier state (17). However, since there were no differences in the recovery rates of BLPO in this study of acutely inflamed tonsils, the increased activity of clindamycin over penicillin in this report cannot be explained by its enhanced activity against BLPO.…”

Section: Discussioncontrasting

confidence: 48%

In vitro and in vivo effects of penicillin and clindamycin on expression of group A beta-hemolytic streptococcal capsule

Brook

Gober

Leyva

1995

Antimicrob Agents Chemother

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Encapsulation of group A beta-hemolytic streptococci (GABHS) is an important virulence factor. The changes that occur in the frequency of encapsulation of GABHS during pharyngotonsillitis, in 20 patients treated with penicillin and 20 treated with clindamycin, were investigated. The effects of subinhibitory concentrations of these agents were also evaluated in vitro. At day 4, 8 of 10 (80%) GABHS isolates recovered from children treated with penicillin were encapsulated, compared with 1 of 5 (20%) of those from children treated with clindamycin (P < 0.05). Two days following 10 days of therapy, GABHS was eliminated from 13 of the 20 (65%) children treated with penicillin and from all treated with clindamycin (P < 0.05). At that time, six of the seven GABHS isolates recovered in patients treated with penicillin were encapsulated. GABHS were not detected after 4 days of therapy in those treated with clindamycin. Incubation of GABHS isolates with one-half of the MIC of clindamycin reduced the frequency of encapsulation, compared with that after incubation with one-half of the MIC of penicillin (12.5 versus 67.5%). These data illustrate the superiority of clindamycin over penicillin in reducing the expression of a capsule by GABHS.The virulence of group A beta-hemolytic streptococci (GABHS) has been associated with two cell wall structures: the M protein and the hyaluronic acid capsule (6, 14). The virulence was assessed by resistance to phagocytosis (6,7,14) and induction of mortality in mice after intraperitoneal inoculation (18). Variation in the elaboration of M protein during the natural course of respiratory infections was observed (14). Compared with characteristics during the acute stages of the infection, about half of GABHS isolates gradually lost their ability to elaborate type-specific M-protein antigen and became susceptible to the antibacterial activity of the human blood during the convalescent and carrier stages. However, variations in the presence of capsule of GABHS and the effects of antimicrobial therapy on expression of a capsule were not evaluated during the different phases of pharyngotonsillitis in children.This study was performed to investigate the dynamics of expression of capsule by GABHS during pharyngotonsillitis in patients treated with penicillin or clindamycin. The in vitro effects of subinhibitory concentrations of these agents were also evaluated. MATERIALS AND METHODSPatients. Children who were seen for acute GABHS pharyngotonsillitis were considered for inclusion in the study. These children had symptoms of acute uncomplicated pharyngotonsillitis of 1 to 4 days' duration. They had sore throats, swollen and enlarged tonsils with or without exudate, tender cervical lymph glands, and temperatures above 38ЊC. More than 10 colonies of GABHS were isolated from their pharyngotonsillar cultures. None had received antimicrobial therapy for the past 6 weeks, and none had had an acute pharyngotonsillar inflammation in the past 3 months. Included in the analysis were the first 20 consecutive...

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Section: Discussioncontrasting

confidence: 48%

In vitro and in vivo effects of penicillin and clindamycin on expression of group A beta-hemolytic streptococcal capsule

Brook

Gober

Leyva

1995

Antimicrob Agents Chemother

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“…There is obviously no problem in treating infections by penicillin-sensitive organisms with cyclacillin [4,10,18,24]. High urinary levels of cyclacillin may favourably influence urinary tract infections with gram-negative rods [3,11], but this is also possible with oral penicillin G [14], as Henri and Klastersky [11] pointed out in this context.…”

Section: Discussionmentioning

confidence: 99%

“…Since then it has been investigated and compared with ampicillin by in vitro studies [7-10, 16, 19, 21, 23, 26, 27, 30], animal experiments [8, 9, 13, 17, 19-21, 23, 26, 30, 31], and con trolled clinical trials [3,4,10,11,18,24], and is meanwhile commercially available for therapy of human infections. Cyclacillin was found to resemble ampicillin in its antibacterial spectrum [26,27,30] and to have pharmaco kinetic advantages over ampicillin, resulting in higher blood levels after oral administration [10,12,19,25,26].…”

mentioning

confidence: 99%

Comparative Assessment of Cyclacillin and Ampicillin by Experimental Therapy and by Serum Level Determinations in Rats and Mice

Freiesleben¹,

Sack²

1976

Chemotherapy

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Therapy of chronic E. coli pyelonephritis in rats was equally effective with cyclacillin and oral ampicillin, whereas intramuscular ampicillin had a significantly higher therapeutic activity than oral cyclacillin. Serum concentrations in rats and mice were consistently higher with cyclacillin than with ampicillin and showed great variations depending on the animal species. It was concluded that there is a good correlation between in vivo and in vitro activity of both antibiotics, provided that the serum levels are taken into consideration. On this basis it may be predicted that in man cyclacillin will exhibit lower therapeutic activity in gram-negative infections than ampicillin.

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“…Plot of eradication rate versus T ϾMIC (assuming a MIC 95 of 0.015 g/ml) achieved over the duration of therapy, i.e., total T ϾMIC, for various penicillin (Pen VK) dose regimens (OE) (4,11,12,13,14,16,18,20,21,22,23,24,25,26,30,31,32,34,37,38,39,40,41,42,43,44,45,49,50) compared to those achieved by amoxicillin sprinkle (f, with 95% confidence interval shown as a bar) (based on average of both doses) and various amoxicillin dose regimens (᭜) (1,8,11,16,33,38) for the treatment of tonsillopharyngitis due to S. pyogenes. Model fit is based on penicillin VK data.…”

Section: Figmentioning

confidence: 99%

Pharmacodynamic Analysis and Clinical Trial of Amoxicillin Sprinkle Administered Once Daily for 7 Days Compared to Penicillin V Potassium Administered Four Times Daily for 10 Days in the Treatment of Tonsillopharyngitis Due to Streptococcus pyogenes in Children

Pichichero

Casey

Block

et al. 2008

Antimicrob Agents Chemother

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An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time above the MIC (T >MIC; based on the MIC 90 of 0.06 g/ml for Streptococcus pyogenes reported in the literature) was shown to be achievable in a phase 1 study of 23 children with a once-daily (QD) modified-release, multiparticulate formulation of amoxicillin (amoxicillin sprinkle). The daily T >MIC achieved with the QD amoxicillin sprinkle formulation was comparable to that achieved with a four-times-daily (QID) penicillin VK suspension. An investigator-blinded, randomized, parallel-group, multicenter study involving 579 children 6 months to 12 years old with acute streptococcal tonsillopharyngitis was then undertaken. Children were randomly assigned 1:1 to receive either the amoxicillin sprinkle (475 mg for ages 6 months to 4 years, 775 mg for ages 5 to 12 years) QD for 7 days or 10 mg/kg of body weight of penicillin VK QID for 10 days (up to the maximum dose of 250 mg QID). Unexpectedly, the rates of bacteriological eradication at the test of cure were 65.3% (132/202) for the amoxicillin sprinkle and 68.0% (132/194) for penicillin VK (95% confidence interval, ؊12.0% to 6.6%). Thus, neither antibiotic regimen met the minimum criterion of >85% eradication ordinarily required by the U.S. FDA for first-line treatment of tonsillopharyngitis due to S. pyogenes. The results of subgroup analyses across demographic characteristics and current infection characteristics and by age/weight categories were consistent with the primary-efficacy result. The clinical cure rates for amoxicillin sprinkle and penicillin VK were 86.1% (216/251) and 91.9% (204/222), respectively (95% confidence interval, ؊11.6% to ؊0.4%). The results of a post hoc PD analysis suggested that a requirement for 60% daily T >MIC 90 more accurately predicted the observed high failure rates for bacteriologic eradication with the amoxicillin sprinkle and penicillin VK suspension studied. Based on the association between longer treatment courses and maximal bacterial eradication rates reported in the literature, an alternative composite PK/PD target taking into consideration the duration of therapy, or total T >MIC, was considered and provides an alternative explanation for the observed failure rate of amoxicillin sprinkle.

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Streptococcal Pharyngitis Therapy: Comparison of Clindamycin Palmitate and Potassium Phenoxymethyl Penicillin

Cited by 49 publications

References 17 publications

In vitro and in vivo effects of penicillin and clindamycin on expression of group A beta-hemolytic streptococcal capsule

In vitro and in vivo effects of penicillin and clindamycin on expression of group A beta-hemolytic streptococcal capsule

Comparative Assessment of Cyclacillin and Ampicillin by Experimental Therapy and by Serum Level Determinations in Rats and Mice

Pharmacodynamic Analysis and Clinical Trial of Amoxicillin Sprinkle Administered Once Daily for 7 Days Compared to Penicillin V Potassium Administered Four Times Daily for 10 Days in the Treatment of Tonsillopharyngitis Due to Streptococcus pyogenes in Children

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