Clinical Trial: Comparative Effectiveness of Cephalexin Plus Trimethoprim-Sulfamethoxazole Versus Cephalexin Alone for Treatment of Uncomplicated Cellulitis: A Randomized Controlled Trial

Pallin, Daniel J.; Binder, William; Allen, Matthew B.; Lederman, Molly; Parmar, Siddharth; Filbin, Michael R.; Hooper, David C.; Camargo, Carlos A.

doi:10.1093/cid/cit122

Cited by 113 publications

(87 citation statements)

References 27 publications

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“…It is possible that S. aureus is not the causative agent in most cases of cellulitis where it was isolated but rather adopts an opportunistic bystander role. This is supported by studies that demonstrate no extra benefit when adding an antibiotic active against MRSA in the presence of detectable MRSA (Pallin et al, 2013). The extensive tissue damage caused by streptococcal toxins may produce an environment that promotes S. aureus multiplicationthis is supported by the detection of both organisms in five of the patients in our study.…”

Section: Discussionsupporting

confidence: 80%

Specific PCR, bacterial culture, serology and pharyngeal sampling to enhance the aetiological diagnosis of cellulitis

Toleman

Vipond

Brindle

2016

Journal of Medical Microbiology

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It is often difficult to obtain a bacteriological diagnosis in patients with cellulitis. We examined the utility of molecular techniques and skin and throat cultures, as well as serology, in providing evidence of either Staphylococcus aureus or group A Streptococcus (GAS) presence in patients with cellulitis. Samples were collected from patients with a clinical diagnosis of cellulitis who were recruited into a prospective placebo-controlled clinical trial (C4C study, EudraCT 2013-001218-14). Specific PCR, paired serology and culture for both organisms were carried out on a variety of samples where appropriate. Despite utilizing a range of diagnostic methods, a bacteriological diagnosis was only achieved in 43 % of patients with a clinical diagnosis of cellulitis. Seventeen per cent of patients tested positive for GAS by any method but only 4 % were positive by PCR, whilst S. aureus was detected in 34% of samples. Bacterial diagnosis in cases of cellulitis remains challenging. This is probably due to a very low bacterial burden with toxin production resulting in inflammation mediating skin damage. Further consideration for the need for long courses of antimicrobial therapy for cellulitis therefore appears merited.

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Section: Discussionsupporting

confidence: 80%

Specific PCR, bacterial culture, serology and pharyngeal sampling to enhance the aetiological diagnosis of cellulitis

Toleman

Vipond

Brindle

2016

Journal of Medical Microbiology

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“…Since more than 90% of community-acquired (CA-MRSA) and hospital acquired (HA-MRSA) strains are still susceptible to trimethoprim-sulfamethoxazole (TMP-SMX, or SXT) (2)(3)(4)(5), new attention has been drawn to this old drug. For example, two recent randomized placebo-controlled studies evaluated the effect of SXT in skin abscesses after incision and drainage in children and adults mostly caused by CA-MRSA (6)(7)(8). Furthermore, De Angelis et al suggested the use of SXT and clindamycin as first-line drugs as a therapeutic option in patients suffering from CA-MRSA infections (9).…”

mentioning

confidence: 99%

Thymidine-Dependent Staphylococcus aureus Small-Colony Variants Are Induced by Trimethoprim-Sulfamethoxazole (SXT) and Have Increased Fitness during SXT Challenge

Kriegeskorte

Lorè

Bragonzi

et al. 2015

Antimicrob Agents Chemother

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dTrimethoprim-sulfamethoxazole (SXT) is a possible alternative for the treatment of community-and hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) due to the susceptibility of most MRSA strains to the drug. However, after longterm treatment with SXT, thymidine-dependent (TD) SXT-resistant small-colony variants (SCVs) emerge. In TD-SCVs, mutations of thymidylate synthase ([TS] thyA) occur. Until now, it has never been systematically investigated that SXT is triggering the induction and/or selection of TD-SCVs. In our study, we performed induction, reversion, and competition experiments in vitro and in vivo using a chronic mouse pneumonia model to determine the impact of SXT on the emergence of TD-SCVs. SCVs were characterized by light and transmission electron microscopy (TEM) and auxotrophism testing. Short-term exposure of S. aureus to SXT induced the TD-SCV phenotype in S. aureus SH1000, while selection of TD-SCVs with thyA mutations occurred after long-term exposure. In reversion experiments with clinical and laboratory TD-SCVs, all revertants carried compensating mutations at the initially identified mutation site. Competition experiments in vitro and in vivo revealed a survival and growth advantage of the ⌬thyA mutant under low-thymidine availability and SXT exposure although this advantage was less profound in vivo. Our results show that SXT induces the TD-SCV phenotype after short-term exposure, while long-term exposure selects for thyA mutations, which provide an advantage for TD-SCVs under specified conditions. Thus, our results further an understanding of the dynamic processes occurring during SXT exposure with induction and selection of S. aureus TD-SCVs.

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“…A recent trial involving 146 patients with uncomplicated cellulitis who were treated with TMP-SMX plus cephalexin or cephalexin alone showed no significant difference in clinical cure rates after 12 days (85% and 82%, respectively; difference, 3 percentage points; 95% confidence interval, −9.3 to 15; P = 0.66). 41 However, the trial was relatively small -powered to detect only a 13% difference in cure rates -and the 95% confidence interval for the difference in these rates could not rule out the superiority of the former regimen. This same comparison of antibiotics for cellulitis is being investigated in one of the large NIH-sponsored studies mentioned above (NCT00729937), which involves approximately 500 participants.…”

Section: Antibiotic Treatmentmentioning

confidence: 97%

Management of Skin Abscesses in the Era of Methicillin-Resistant Staphylococcus aureus

2014

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Clinical Trial: Comparative Effectiveness of Cephalexin Plus Trimethoprim-Sulfamethoxazole Versus Cephalexin Alone for Treatment of Uncomplicated Cellulitis: A Randomized Controlled Trial

Abstract: NCT00676130.

Cited by 113 publications

References 27 publications

Specific PCR, bacterial culture, serology and pharyngeal sampling to enhance the aetiological diagnosis of cellulitis

Specific PCR, bacterial culture, serology and pharyngeal sampling to enhance the aetiological diagnosis of cellulitis

Thymidine-Dependent Staphylococcus aureus Small-Colony Variants Are Induced by Trimethoprim-Sulfamethoxazole (SXT) and Have Increased Fitness during SXT Challenge

Management of Skin Abscesses in the Era of Methicillin-Resistant Staphylococcus aureus

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