Article

Monotherapy versus Multi-Drug Therapy for the Treatment of Perforated Appendicitis in Children

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Children with perforated appendicitis often have a prolonged hospital course complicated by surgical site or intra-abdominal infections. Treatment with multiple intravenous (IV) antibiotics after appendectomy has been the standard of care for these patients. We have recently adopted a protocol using piperacillin-tazobactam (PT) as a single agent in lieu of the standard multi-drug regimen (MD). We hypothesized that PT would be as effective as MD in reducing postoperative complications and would result in decreased resource utilization. We reviewed the medical records of all children admitted to our hospital between January 1, 1998 and December 31, 2001 with the diagnosis of perforated appendicitis. Patients who underwent operation within the first 24 h of admission were divided into two groups based on their antibiotic regimen: PT versus MD. Demographic data, duration of presenting symptoms, initial WBC, length of stay, and infectious complications were abstracted. Categorical data were compared using Chi square analysis; continuous variables were compared using Student's t-test when the data were normally distributed and the Mann-Whitney U test when the data were skewed. There was no difference between the PT (n = 51) and MD (n = 43) groups with respect to age, duration of presenting symptoms, initial WBC, or length of hospital stay. However, patients in the MD group had a significantly higher overall complication rate than those in the PT group (14/43 vs. 4/51, p = 0.002). Antibiotic-related complications including surgical site infections, venous catheter-related infections, intra-abdominal abscesses, and drug reactions were also higher in the MD group (10/43 vs. 4/51, p = 0.04). The outpatient charges for each patient based on an average of seven days of home antibiotics were $2,460 for the PT group and $4,349 for the MD group. Children with perforated appendicitis can be managed effectively with a single broad-spectrum antibiotic after appendectomy. Monotherapy is not only more efficacious than multi-drug therapy, but may be more cost effective. The use of monotherapy for children with perforated appendicitis after adequate source control should be considered the treatment of choice.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... However, newer antibiotics may decrease the number of days needed for antimicrobial therapy, the total number of doses required, and the side effects of therapy. There are several studies amounting to evidence (Grade B) that broad-spectrum, single, or double agent therapy is as effective as and more costeffective than triple agent therapy6789. A prospective, randomized trial conducted by St Peter et al [6] showed single daily dosing of ceftriaxone and metronidazole was more efficient, cost-effective, and had similar results compared to triple antibiotics. ...
... A prospective, randomized trial conducted by St Peter et al [6] showed single daily dosing of ceftriaxone and metronidazole was more efficient, cost-effective, and had similar results compared to triple antibiotics. A retrospective study showed piperacillin-tazobactam was more cost-effective and had similar results compared to triple antibiotics in patients with perforated appendicitis [7] . A prospective trial compared triple antibiotics to piperacillintazobactam administered for 10 days showed outcomes that are similar to the triple antibiotic therapy described by Lund and Murphy [5]. ...
... Comparing the cost of different antibiotic regimens is difficult to assess as most of the cost will be because of the length of hospitalization and morbidity rate. However, because studies have shown similar efficacy with respect to morbidity and length of hospitalization6789, then we would expect the overall costs for the different regimens to be similar. When directly comparing the cost of the antibiotics, inpatient antibiotic charges for ceftriaxone and metronidazole was significantly less than for triple antibiotics ($1413 ± $782 vs $1940 ± $633; P b .001) ...
Article
The aim of the study was to review evidence-based data regarding the use of antibiotics for the treatment of appendicitis in children. Data were obtained from PubMed, MEDLINE, and citation review. We conducted a literature search using "appendicitis" combined with "antibiotics" with children as the target patient population. Studies were selected based on relevance for the following questions: (1) What perioperative antibiotics should be used for pediatric patients with nonperforated appendicitis? (2) For patients with perforated appendicitis treated with appendectomy: a. What perioperative intravenous antibiotics should be used? b. How long should perioperative intravenous antibiotics be used? c. Should oral antibiotics be used? (3) For patients with perforated appendicitis treated with initial nonoperative management, what antibiotics should be used in the initial management? Children with nonperforated appendicitis should receive preoperative, broad-spectrum antibiotics. In children with perforated appendicitis who had undergone appendectomy, intravenous antibiotic duration should be based on clinical criteria. Furthermore, broad-spectrum, single, or double agent therapy is as equally efficacious as but is more cost-effective than triple agent therapy. If intravenous antibiotics are administered for less than 5 days, oral antibiotics should be administered for a total antibiotic course of 7 days. For children with perforated appendicitis who did not initially undergo an appendectomy, the duration of broad-spectrum, intravenous antibiotics should be based on clinical symptoms. Current evidence supports the use of guidelines as described above for antibiotic therapy in children with acute and perforated appendicitis.
... 6 Increasing evidence suggests that single-agent antibiotic therapy provides equivalent results, compared with multiagent regimens. [7][8][9] The aim of the study is to compare the surgical outcome of laparoscopic appendectomy in children for perforated appendicitis using perioperative triple versus a single antibiotic based regimen. ...
... In accordance to Nadler et al, 9 there was statistically significant difference between both groups (13% versus 36% in MG and TG respectively) for the need to replace the IV cannula before 72 hours, which is attributed to the occurrence of thrombophlebitis due to frequent injections. As IV cannula insertion is very annoying procedure in children, even with the use of local anesthetic during insertion, we think venous access morbidities should be always looked for in planning antibiocs management in children. ...
... Recent studies have compared the efficacy of antimicrobial therapy with multiple drugs (ampicillin, clindamycin and gentamicin) or single drugs (piperacillin/tazobactam) in preventing post-operative complications and reducing costs [2] [3]. ...
... In patients with acute appendicitis, timing of surgery does not seem to increase the risk of complications like perforation and wound infection [1] [2]. Employing medical imaging techniques such as ultrasound and computed tomography may be valuable to perform an early diagnosis and to guide treatment in order to prevent complications, regardless of the timing of surgery [2] [3]. Acute appendicitis, even when uncomplicated, is still considered an emergency, though some authors have reported that postponing surgery up to 18 hours after admission does not increase the rate of complications [4] [5]. ...
... This agent is used frequently for the treatment of patients with serious infections because of E. faecalis, such as endocarditis or bacteremia [325,326]. Ampicillin has been used frequently also as a component of combination (''triple'') antibiotic therapy for IAI, particularly in pediatric patients, although its necessity for that has not been demonstrated [204,327,328]. The task force has concluded that ampicillin is an acceptable agent for managing a proven or suspected IAI because of E. faecalis in higher-risk patients, if the selected regimen lacks activity against that micro-organism. ...
... surgical-infections/53/. These RCTs support use of ticarcillinclavulanic acid [220,662,663], piperacillin-tazobactam [225,327], ertapenem [205,214,220], imipenem-cilastatin [664,665], meropenem [290,666], cefoperazone-sulbactam [203], and combinations of cefotaxime [225,667], ceftriaxone [204,212,319,668], or ceftazidime [210] with metronidazole or clindamycin. In addition, cefuroxime has been approved for use in pediatric patients [523], and cefepime [669] and aztreonam [670] have efficacy for managing serious pediatric infections, although studies have not specifically addressed their use in pediatric IAI. ...
Article
Full-text available
Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline.
... The incidence of SSI after appendectomy has been reported to range from 0 to 11 % [155][156][157][158][159][160][161][162][163][164]. The severity of appendicitis strongly influences the risk of developing post-operative complications resulting in a substantially higher complication rate (up to 2-4 times) in patients with complicated appendicitis. ...
... Available evidence on duration of treatment is limited and mainly focused on children. However, there is no firm evidence on the duration (3, 5, 7, 10 days) and route of administration (usually intravenous administration for 48 h, then oral administration) [156,157,159,161,162]. ...
Article
Full-text available
Unequivocal international guidelines regarding the diagnosis and management of patients with acute appendicitis are lacking. The aim of the consensus meeting 2015 of the EAES was to generate a European guideline based on best available evidence and expert opinions of a panel of EAES members. After a systematic review of the literature by an international group of surgical research fellows, an expert panel with extensive clinical experience in the management of appendicitis discussed statements and recommendations. Statements and recommendations with more than 70 % agreement by the experts were selected for a web survey and the consensus meeting of the EAES in Bucharest in June 2015. EAES members and attendees at the EAES meeting in Bucharest could vote on these statements and recommendations. In the case of more than 70 % agreement, the statement or recommendation was defined as supported by the scientific community. Results from both the web survey and the consensus meeting in Bucharest are presented as percentages. In total, 46 statements and recommendations were selected for the web survey and consensus meeting. More than 232 members and attendees voted on them. In 41 of 46 statements and recommendations, more than 70 % agreement was reached. All 46 statements and recommendations are presented in this paper. They comprise topics regarding the diagnostic work-up, treatment indications, procedural aspects and post-operative care. The consensus meeting produced 46 statements and recommendations on the diagnostic work-up and management of appendicitis. The majority of the EAES members supported these statements. These consensus proceedings provide additional guidance to surgeons and surgical residents providing care to patients with appendicitis. Electronic supplementary material The online version of this article (doi:10.1007/s00464-016-5245-7) contains supplementary material, which is available to authorized users.
... The same study showed that most surgeons choose a triple "standard therapy" comprising an aminoglycoside, a β-lactam and a regimen covering anaerobes. However, there is growing evidence that broad-spectrum single (piperacillin/tazobactam) or double-agent (ceftriaxone + metronidazole) therapy is equally effective and less expensive than triple-agent therapy and may lead to a shorter LOS [67][68][69][70] . This is in line with the recommendations of the American Pediatric Surgical Association (APSA) that state that broad-spectrum single or double-agent therapy is equally efficient and more cost-effective than three drugs [65] . ...
Article
Full-text available
Complicated acute appendicitis (CAA) is a serious condition and carries significant morbidity in children. A strict diagnosis is challenging, as there are many lesions that mimic CAA. The management of CAA is still controversial. There are two options for treatment: Immediate operative management and non-operative management with antibiotics and/or drainage of any abscess or phlegmon. Each method of treatment has advantages and disadvantages. Operative management may be difficult due to the presence of inflamed tissues and may lead to detrimental events. In many cases, non-operative management with or without drainage and interval appendectomy is advised. The reasons for this approach include new medications and policies for the use of antibiotic therapy. Furthermore, advances in radiological interventions may overcome difficulties such as diagnosing and managing the complications of CAA without any surgeries. However, questions have been raised about the risk of recurrence, prolonged use of antibiotics, lengthened hospital stay and delay in returning to daily activities. Moreover, the need for interval appendectomy is currently under debate because of the low risk of recurrence. Due to the paucity of high-quality studies, more randomized controlled trials to determine the precise management strategy are needed. This review aims to study the current data on operative vs non-operative management for CAA in children and to extract any useful information from the literature.
... Currently, there are many antibiotic protocols used for the treatment of diffuse peritonitis attributable to perforated appendicitis following appendectomy by pediatric surgeons, as there are many opinions regarding choice of antibiotic, route of administration (oral or parenteral), and duration of treatment [6,8]. Recent studies have shown that monotherapy with newer broad-spectrum antibiotics has been as effective as combination therapy [6,9]. Many studies have shown that ertapenem is a valuable antibiotic against the bacteria most commonly isolated in children with intra-abdominal infections, but on the other hand, in patients with hospitalacquired infections infected with organisms such as Pseudomonas aeruginosa or enterococci, ertapenem is not the drug of choice [10]. ...
Article
Full-text available
Background: This study evaluated the efficacy and safety of ertapenem versus a combination of gentamicin plus metronidazole in pediatric patients with diffuse peritonitis attributable to perforated appendicitis. Methods: From January 2017 to January 2019, 80 pediatric patients with a median age of 13 years who underwent laparoscopic appendectomy because of perforated appendicitis with diffuse peritonitis were enrolled. The patients were randomly assigned to two groups of 40 patients each to receive ertapenem or combination therapy. The groups were compared regarding demographic/clinical data and outcomes of treatment. The main outcome measures were duration of hospitalization, time to achieving an afebrile state, post-operative complications, antibiotic treatment failure, and time to the start of enteral feeding. Results: The median length of the hospital stay was 5 and 8 days in the ertapenem and combination therapy groups, respectively (p < 0.0001). Patients in the ertapenem group took two days less to become afebrile (p < 0.0001). No post-operative complications were recorded in the ertapenem group, whereas in the combination therapy group, three complications were noted, but this difference was not significant (p = 0.2392). Furthermore, all patients in the ertapenem group responded to therapy, whereas in the combination therapy group, two antibiotic treatment failures were recorded, a diffrence that again was not significant (p = 0.4739). There was no difference in the time to the start of enteral feeding in the two groups. Conclusion: Both ertapenem and gentamicin plus metronidazole are safe and effective therapeutic options for the treatment of diffuse peritonitis in pediatric patients. Treatment with ertapenem results in lower complication rates, a shorter time to an afebrile state, and a shorter hospital stay.
... Combined triple therapy (e.g., amoxicillin + aminoglycoside + metronidazole) has been widely used [1,8,9]. However, recent evidence suggests that a broad-spectrum, single antibiotic therapy (e.g., piperacillin-tazobactam) [10][11][12] or a combination of ceftriaxone and metronidazole [13][14][15] are at least as effective and economical [16]. ...
Article
Full-text available
Background: Choice of antibiotics for complicated appendicitis should address local antibiotic resistance patterns. As our local data showed a less than 15% resistance of Escherichia coli to co-amoxicillin (amoxicillin + clavulanic acid), we opted for this antibiotic in 2013. Subsequently, the increasing prevalence of Pseudomonas aeruginosa challenged this choice. Aim of the study: The aim of this study was to describe the bacteriology of peritoneal swabs from cases of complicated appendicitis in our paediatric patients, and to determine the risk of infectious complications (wound and/or intra-abdominal abscesses). Methods: We designed a retrospective cohort study including all children (<18 years old) who had surgery for complicated appendicitis between 1 January 2010 and 31 December 2016 and had a peritoneal swab culture. Microbiological results are presented descriptively. Univariate analyses were performed for potential determinants of infectious complications. All variables with a p-value <0.05 were then included in a multivariable logistic regression model, for which adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results: One hundred and thirty-three patients were treated for complicated appendicitis and had cultures of peritoneal fluid. Median age was 9.5 years old (IQR 5.7–12.4), and there were 53 girls (40%). E. coli was isolated in 94 patients (71%) and was resistant to co-amoxicillin in 14% of cases. P. aeruginosa was isolated in 31 patients (23%). The rate of infectious complications was 38% (8/21 patients) when the empiric antibiotic did not cover P. aeruginosa and 0% (0/10 patients) when P. aeruginosa was covered adequately (p = 0.03). In a multivariable analysis, only co-amoxicillin-resistant E. coli significantly predicted infectious complications (OR 4.7; 95% CI 1.4–16.6; p = 0.015). Conclusion: Results of the multivariable analysis of this small, retrospective study revealed a statistically significant increase in the risk of postoperative complications in the presence of co-amoxicillin-resistant E. coli. The choice of antibiotic should be adapted accordingly. More data are needed to justify the systematic coverage of P. aeruginosa in children with complicated appendicitis. &nbsp.
... This is driven largely by the fewer infusions required by other regimens. Retrospective, historical, and case-control single-center reviews have examined multiple clinical and costrelated outcomes of traditional aminoglycoside-based triple antibiotic therapy regimens, compared with non-aminoglycoside-based regimens, and have demonstrated at least equivalent efficacy [131][132][133]. A large review of data on discharge diagnoses ( ) from the Pediatric Health Inforn p 8545 mation database for 32 children's hospitals in the United States was recently completed and found that there was significant and substantial improvement in terms of length of stay, pharmacy charges, and hospital charges, with no increase in hospital readmissions, among children receiving monotherapy, compared with those receiving traditional triple-antibiotic therapy [130]. ...
Article
BACKGROUND Antimicrobial resistance and inappropriate antibiotic regimen hamper a favorable outcome in intra-abdominal infections. Clinicians rely on the minimum inhibitory concentration (MIC) value to choose from the susceptible antimicrobials. However, the MIC values cannot be directly compared between the different antibiotics because their breakpoints are different. For that reason, efficacy ratio (ER), a ratio of susceptible MIC breakpoint and MIC of isolate, can be used to choose the most appropriate antimicrobial. MATERIALS AND METHODS A prospective, observational study conducted during 2015 and 2016 included 356 Escherichia coli and 158 Klebsiella spp. isolates obtained from the intra-abdominal specimens. MIC was determined by microbroth dilution method, and ER of each antibiotic was calculated for all the isolates. RESULTS For both E. coli and Klebsiella spp., ertapenem, amikacin, and piperacillin/tazobactam had the best activities among their respective antibiotic classes. DISCUSSION This is the first study calculating ER for deciding empiric treatment choices. ER also has a potential additional value in choosing the use of susceptible drugs as monotherapy or combination therapy. A shift in ERs over a period of time tracks rising MIC values and predicts antimicrobial resistance development. CONCLUSION Estimation of ER could be a meaningful addition for the interpretation of an antimicrobial susceptibility report, thus helping the physician to choose the best among susceptible antimicrobials for patient management.
... 6 Monotherapy regimens such as piperacillin/tazobactam have been found to be equally advantageous; however, they are more expensive than the dual antibiotic regimens. 7,8 Our current regimen of ceftriaxone and metronidazole dosed once daily was adopted from St Peter et al. 6 Some studies support a defined length of antibiotic treatment whereas others follow institutional clinical practice guidelines. 6, 9e11 No defined consensus on treatment length exists for the administration of oral antibiotics at home. ...
Article
Background: Variation exists for postoperative antibiotics in children with complicated appendicitis. We investigated the impact of white blood count (WBC) at discharge on oral antibiotic therapy, abscess rate, and readmission rate. Material/methods: We conducted a two year review of children with complicated appendicitis. In the pre-protocol group, total antibiotic therapy was ten days (IV and oral) and home oral antibiotics at discharge. In the post-protocol group, children with leukocytosis were prescribed oral antibiotics to complete seven days of total antibiotic therapy and children without leukocytosis were not prescribed oral home antibiotics. Results: There was no difference between mean hospital days after operation (3.52 vs. 3.24, p = 0.5111), means days of inpatient intravenous antibiotics (3.13 vs. 2.58, p = 0.5438), post-operative abscess rates (20.7% vs. 19.6%, p = 0.9975), or readmission rate (13.4% vs. 12.4%, p = 1.000). The post-protocol group had a shorter average total antibiotic duration (4.24 vs. 9.52 days, p < 0.001) and were more likely to be discharged without oral antibiotics (71.1% vs 8.5%, p < 0.001). Discussion: Limiting home antibiotics at discharge to children with leukocytosis significantly decreases home antibiotic use.
... A study done by Nadler Et al suggested a single drug higher antibiotic therapy for complicated appendicitis , but such a step lead to increased wound infection in our set of patients. [16] The duration of antibiotic should be 3-5 days in non perforated group where as it is 7 -9 days in perforated group. ...
... The baseline characteristics of our patient population and the outcomes observed were similar to those reported in the literature. [3][4][5][6][7][8] While the Lee, et al difference in infectious complications between the 2 groups was not statistically significant, the twofold greater risk in those receiving ceftriaxone and metronidazole was concerning. One possible source for this difference may be inadequate antimicrobial coverage. ...
Article
Objectives: The aim of this study was to compare hospital length of stay and rate of infectious complications in children with perforated appendicitis based on the postoperative antibiotic administered. Methods: This study was a retrospective analysis of children with perforated appendicitis who underwent an appendectomy at a large academic medical center from 2008 to 2013. The primary outcome was hospital length of stay. The secondary outcomes were rates of abscess formation, wound infection, and 30-day readmissions. Results: One hundred and twenty-three patients were included. Sixty-six patients (53%) were administered ceftriaxone and metronidazole once daily; 57 (47%) were administered other antibiotic regimens, which consisted of single, double, or triple antibiotic therapy with a beta-lactam backbone. There was no difference between the groups in terms of postoperative length of stay (5.7 versus 5.8 days, p = 0.83), postoperative abscess rate (8% versus 4%, p = 0.57), postoperative wound infection rate (5% versus 2%, p = 0.73), and 30-day readmissions (3% versus 11%, p = 0.19). Conclusions: While there was no statistically significant difierence in the outcomes evaluated, the rate of infectious complications was twofold higher in those given ceftriaxone and metronidazole than in others. A larger prospective randomized controlled trial is warranted to better understand the risks of using these agents.
... Consequently, ceftriaxone is contraindicated for use in hyperbilirubinemic neonates and for use concurrently or within 48 h of calcium-containing intravenous (IV) solutions in neonates. However, in the pediatric population, a simplified regimen of ceftriaxone and metronidazole has been shown to be as safe and effective as ampicillin, gentamicin, and metronidazole or clindamycin for the treatment of complicated appendicitis [26,27]. Unlike the other b-lactam antimicrobials, ceftriaxone only requires dose adjustment when a patient has both renal and hepatic impairment [23]. ...
Article
Complicated intra-abdominal infections (cIAIs) are an important cause of morbidity and mortality worldwide. They are diagnosed when the initial abdominal organ infection has spread into the peritoneal space. Successful treatment relies on adequate source control and appropriate empiric antimicrobial therapy. Inappropriate antimicrobial therapy may result in poor patient outcomes and increases in healthcare costs. Current guidelines recommend several single and combination antimicrobial regimens; however, empiric antimicrobial treatment has been complicated by the increasing rates of resistant organisms, especially the extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Additionally, the overuse of carbapenems to combat these resistant pathogens has contributed to the rise of carbapenemase-producing microorganisms, especially Klebsiella pneumoniae. This increasing resistance has prompted the development of novel antimicrobials like ceftazidime-avibactam and ceftolozane-tazobactam, whose activity extends to ESBL-producing microorganisms. Furthermore, the optimal duration of antimicrobial therapy is still unknown, and further research is necessary to find a definitive answer. This review will focus on antimicrobial therapies recommended by the current guidelines, the individual properties of these agents, appropriate duration of therapy, recent clinical trials, and place in therapy of the antimicrobial agents recently approved for the treatment of cIAIs.
... The practice of 'polypharmacy' or Multiple Drug Therapy, especially in patients with multiple complications, has resulted in some serious clinical drug-drug interactions (HemaIswarya and Doble, 2006 andNadler, et al., 2003). This is one of the major causes of withdrawal of drugs (such as terfenadine and cerivastatin) from the market during the past few years (Wienkers and Heath, 2005). ...
Article
Formononetin (FMN) and Biochanin A (BCA) are the principal isoflavones present in commercially available extracts of red clover that are widely been consumed for various health benefits. We investigated the in vitro effects of FMN and BCA on catalytic activity of human/rat cytochrome P450 enzymes to assess the drug interaction potential of red clover. IC50 and Ki values of FMN and BCA for CYPs were determined in human/rat liver microsomes. FMN and BCA showed concentration-dependent inhibition of CYP1A2 activity with IC50 values of 13.42 and 24.98 μM in human liver microsomes and 38.57 and 11.86 μM in rat liver microsomes, respectively. The mode of inhibition of human CYP1A2 by FMN was found to be competitive with apparent Ki value of 10.13±1.96 μM. FMN also inhibited human CYP2D6. BCA exerted moderately inhibitory effects on human CYP2C9. The predicted in vivo inhibition for CYP1A2 was insignificant (R value < 1.1) at hepatic level while at intestinal level, it was significant (R value > 11). The inhibitory effects on other CYPs were found to be minimal. Red clover may be considered safe to be consumed along with co-prescribed medications; however, precaution must be taken while co-administering it with CYP1A2 substrates.
... [106] Adequate empirical treatment should be started preoperatively in order to minimize the risk of infective complications. [85] [104] 2 Regular dose Ampicillin, gentamicin and clindamycin [165, 166] 3 Once daily ceftriaxone and metronidazole [165] 4 Ticarcillin/clavulanate and Gentamycin [167] 5 Piperacillin/Tazobactam monotherapy [147, 168, 169] 6 Cefotaxime and metronidazole combination therapy [170] 7 Co-amoxiclav, metronidazole and gentamicin therapy [85] 8 Clindamycin and Ceftazidime [121] Scant data exists about optimal duration of post-operative antibiotic treatment. [56] Some authors advocate a predefined duration of antimicrobial treatment based on protocol rather than clinical criteria, whereas others discontinue antibiotics depending on the patient's clinical signs, regardless of the length of the patient's therapy. ...
Chapter
Full-text available
Introduction: Advanced appendicitis (perforation, mass, or abscess) is a significant cause of morbidity in children. This chapter reviews the risk factors for and the management of children with advanced appendicitis and associated complications. Methods: A search of the literature was conducted and manual cross-referencing was performed. Results: The incidence of perforation and outcomes vary according to age, gender, and geographical region. Advanced appendicitis is unlikely in the presence of a normal white blood cell (WBC) or C-reactive protein (CRP) measurement. The presence of fever, symptom duration > 24h, generalized abdominal tenderness, rebound tenderness and or rigidity, hypoactive and/or absent bowel sounds, right lower quadrant mass, leukocytosis, and fecalith on CT scans may suggest advanced appendicitis. Age, increased BMI, diarrhea, inadequate antibiotic therapy, and certain microbial isolates may predispose an individual to an increased risk of post-appendectomy complications. Discussion: Non-operative, operative, and postoperative management strategies in the treatment of pediatric advanced appendicitis are discussed. The key to reducing complications is early diagnosis of advanced appendicitis, which is aided by robust decision-making, biomarker analysis, and the judicious use of imaging. Conclusion: An up-to-date review of the risk factors for and management of children with advanced appendicitis and complications is presented.
... The impetus for defining a simplified postoperative antibiotic regimen is a strong one. Monotherapy with newer broad-spectrum agents such as piperacillin/tazobactum for intraabdominal infections has recently been demonstrated to be equally efficacious as traditional triple therapy [14,15]. Similarly, cefotaxime, a cephalosporin with a similar profile to ceftriaxone, has been shown to be equal to the aforementioned monotherapy schedule of piperacillin/tazobactum in children with complicated perforated appendicitis when combined with metronidazole [16]. ...
Article
Full-text available
OBJECTIVE: Appendicitis is the most common abdominal emergency in children. When perforation is encountered, postoperative management is grounded upon the use of intravenous antibiotics. The 3-drug regimen of ampicillin, gentamicin, and clindamycin has long been the accepted standard by pediatric surgeons. Although effective and seemingly inexpensive, this regimen produces a cumbersome dosing schedule, which has inspired the search for a simpler regimen that does not compromise efficacy or expense. To this end, we have introduced a 2-drug regimen of ceftriaxone and Flagyl (Pharmacia Corporation, Chicago, Ill) with once-a-day dosing. METHODS: A retrospective review was conducted of the most recent 250 patients treated at our institution with perforated appendicitis. Patients treated since the implementation of this 2-drug regimen were compared with the recent historical cohort treated with triple antibiotic coverage. Parameters analyzed between the 2 groups included temperature curves for the first 5 postoperative days, abscess rate, length of hospitalization, length of intravenous antibiotic treatment, and medication charges. RESULTS: The 2-drug regimen was used in 57 patients (group 1) compared with 193 patients treated with triple antibiotic coverage (group 2). Maximum recorded temperature between the 2 groups was similar upon admission, but the mean maximum temperature in group 1 became significantly lower than group 2 from postoperative day 1 onward (P < .001). Postoperatively, an abscess developed in 8.8% of group 1 compared with 14.2% of group 2, which was not significantly different (P = .37). Mean length of stay was 6.8 days in group 1 and 7.8 days in group 2 (P = .03). Medication charges to the patient were 81.32 dollars per day in group 1 compared with 318.53 dollars per day in group 2, translating to 1186.05 dollars savings for 5 days. CONCLUSIONS: Once-a-day dosing with ceftriaxone and Flagyl provides adequate antibiotic coverage for the postoperative management of perforated appendicitis in children. This regimen allows patients to more rapidly defervesce compared with traditional triple antibiotic coverage; moreover, this simple regimen provides substantial advantages for administration and expense.
... (4) Since then studies have demonstrated the safety and efficacy of using shorter time courses of antibiotics, single-agent regimens, and completing intravenous (IV) antibiotics at home using a peripherally inserted central catheter (PICC) compared to continued hospitalization. (5)(6)(7)(8) Furthermore, there is now evidence that an oral (PO) antibiotic regimen is equivalent to IV administration with respect to disease-related complications, such as intra-abdominal abscesses and wound infections, while reducing overall costs. (9)(10)(11)(12) PICCs do have some potential advantages in hospitalized children including providing stable intravenous access which decreases the number peripheral IV insertions throughout the hospital course and allows for blood sample collection without phlebotomy. ...
Article
The purpose of this study was to compare postoperative outcomes of pediatric patients with complicated appendicitis managed with or without a peripherally inserted central catheter (PICC). Patients aged ≤18 y in the Pediatric Health Information System database with complicated appendicitis that underwent appendectomy during their index admission in 2000-2012 were grouped by whether they had a PICC placed using relevant procedure and billing codes. Rates of subsequent encounters within 30 d of discharge along with associated diagnoses and procedures were determined. A propensity score-matched (PSM) analysis was performed to account for differences in baseline exposures and severity of illness. We included 33,482 patients with complicated appendicitis; of whom, 6620 (19.8%) received a PICC and 26,862 (80.2%) did not. The PICC group had a longer postoperative length of stay (median 7 versus 5 d, P < 0.001) and were more likely to undergo intra-abdominal abscess drainage during the index admission (14.4% versus 2.1%, P < 0.001), and have a reencounter (17.5% versus 11.4%, P < 0.001) within 30 d of discharge. However, in the PSM cohort (n = 4428 in each group), outcomes did not differ between treatment groups, although the PICC group did have increased odds for the development of other postoperative complications (odds ratio = 3.95, 95% confidence interval: 1.45, 10.71). After accounting for differences in severity of illness by PSM, patients managed with PICCs had a similar risk for nearly all postoperative complications, including reencounters. Postoperative management of pediatric complicated appendicitis with a PICC is not clearly associated with improved outcomes.
... Complete antimicrobial coverage may be achieved using multiple agents [7,10,[12][13][14][15][16]. However, targeted antibiotic treatment is preferable in the interest of decreasing resistance [1,[17][18][19]. ...
Article
Full-text available
The aim of this study was to investigate the microbiology of secondary bacterial peritonitis due to appendicitis and the appropriateness of current antimicrobial practice in one institution. A 14-year retrospective single-centre study of 69 consecutive paediatric patients (age 1-14 years) with appendicitis-related peritonitis and positive peritoneal specimen cultures was conducted. Post-operative outcomes, microbiology and antibiotic susceptibility of peritoneal isolates were analysed in all patients. Escherichia coli was identified in 56/69 (81 %) peritoneal specimens; four isolates were resistant to amoxicillin-clavulanate, and one other isolate was resistant to gentamicin. Anaerobes were identified in 37/69 (54 %) peritoneal specimens; two anaerobic isolates were resistant to amoxicillin-clavulanate and one isolate was resistant to metronidazole. Pseudomonas aeruginosa was identified in 4/69 (6 %) peritoneal specimens, and all were susceptible to gentamicin. Streptococcal species (two Group F streptococci and three β-haemolytic streptococci) were identified in 5/69 (7 %) specimens, and all were susceptible to amoxicillin-clavulanate. Combination therapy involving amoxicillin-clavulanate and aminoglycoside is appropriate empirical treatment in 68/69 (99 %) patients. Addition of metronidazole to this regime would provide 100 % initial empirical coverage. Inadequate initial empiric antibiotic treatment and the presence of amoxicillin-clavulanate resistant E. coli were independent predictors of the post-operative infectious complications observed in 14/69 (20 %) patients. E. coli and mixed anaerobes are the predominant organisms identified in secondary peritonitis from appendicitis in children. Inadequate initial empirical antibiotic and amoxicillin-clavulanate resistant E. coli may contribute to increased post-operative infectious complications. This study provides evidence-based information on choice of combination therapy for paediatric appendicitis-related bacterial peritonitis.
... Tiene por lo tanto una importancia trascendente. Su diagnóstico y tratamiento oportuno es objeto de constante análisis [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . ...
Article
Full-text available
Introducción: La infección de la herida operatoria es una de las complicaciones más importantes en los pacientes apendicectomizados, y en especial los de apendicitis aguda perforada. Se diseñó un método simple para la detección precoz de esta complicación: Cultivo de punto centinela. El objetivo de este estudio es la validación de este procedimiento como método de diagnóstico precoz de los pacientes que evolucionarán con infección de herida operatoria. Materiales y Métodos: El punto centinela consiste en el cultivo de un material de sutura trenzado instalado en el tejido subcutáneo de la herida operatoria, que se retira a las 24-48 h postoperatorias. Se obtuvo una muestra de pacientes operados por apendicitis aguda perforada en el Hospital Herminda Martin de Chillán desde Octubre del 2004 hasta Marzo del 2005, según criterios de selección establecidos. Los cultivos ( ± ) se compararon con una evaluación clínica que evidenciara una infección de herida operatoria (Gold Standard) y se analizó su coeficiente de probabilidad (CP). Resultados: Durante el estudio se operaron 129 pacientes de apendicitis aguda perforada (30,4% de todas las apendicitis). Se incluyó en el análisis a 46 y se les aplicó el método. Se obtuvo una sensibilidad de 91,1%, una especificidad de 97,1 porcentaje, un CP de cultivos (+) de 31,2, y un CP de cultivos (-) de 0,09. Discusión: El método descrito es simple y efectivo en la detección precoz de infección de herida operatoria. Se requiere mayor estudio para determinar cuán anticipado es sobre otras metodologías, así como su costo-beneficio y su utilización en otras patologías que evolucionan con infección de herida operatoria.
... Monotherapy with piperacillin/tazobactam for intra-abdominal infections has recently been shown to be equally efficacious as traditional triple therapy. 5,6 Similarly, cefotaxime, a third-generation cephalosporin, has been shown to be equal to the monotherapy schedule of piperacillin/tazobactam in children with complicated perforated appendicitis when combined with metronidazole. 7 Piperacillin/tazobactam has the disadvantage of costly individual doses and patients still usually require 3 to 4 doses per day. ...
Article
Full-text available
The optimal management for children with complicated appendicitis remains unclear. However, our group has been interested in this disease, and has initiated several prospective randomized trials looking at various aspects of the care of these patients. In this article, we will discuss our definition of perforated appendicitis and how it was derived. We will also discuss a prospective randomized trial looking at the optimal antibiotic regimen and its relative place in the literature as well the data we have generated on the length of antibiotic therapy. We will also review the available data on the timing and necessity of appendectomy for perforated appendicitis. Finally, we will discuss the management of the difficult subset of patients who present with a well-defined abscess.
... This is driven largely by the fewer infusions required by other regimens. Retrospective, historical, and case-control single-center reviews have examined multiple clinical and costrelated outcomes of traditional aminoglycoside-based triple antibiotic therapy regimens, compared with non–aminoglycoside-based regimens, and have demonstrated at least equivalent efficacy131132133 . A large review of data on discharge diagnoses ( ) from the Pediatric Health Inforn p 8545 mation database for 32 children's hospitals in the United States was recently completed and found that there was significant and substantial improvement in terms of length of stay, pharmacy charges, and hospital charges, with no increase in hospital readmissions, among children receiving monotherapy, compared with those receiving traditional triple-antibiotic therapy [130]. ...
Article
Full-text available
Evidence-based guidelines for managing patients with intra-abdominal infection were prepared by an Expert Panel of the Surgical Infection Society and the Infectious Diseases Society of America. These updated guidelines replace those previously published in 2002 and 2003. The guidelines are intended for treating patients who either have these infections or may be at risk for them. New information, based on publications from the period 2003–2008, is incorporated into this guideline document. The panel has also added recommendations for managing intra-abdominal infection in children, particularly where such management differs from that of adults; for appendicitis in patients of all ages; and for necrotizing enterocolitis in neonates.
... This is driven largely by the fewer infusions required by other regimens. Retrospective, historical, and case-control single-center reviews have examined multiple clinical and costrelated outcomes of traditional aminoglycoside-based triple antibiotic therapy regimens, compared with non-aminoglycoside-based regimens, and have demonstrated at least equivalent efficacy [131][132][133]. A large review of data on discharge diagnoses ( ) from the Pediatric Health Inforn p 8545 mation database for 32 children's hospitals in the United States was recently completed and found that there was significant and substantial improvement in terms of length of stay, pharmacy charges, and hospital charges, with no increase in hospital readmissions, among children receiving monotherapy, compared with those receiving traditional triple-antibiotic therapy [130]. ...
Article
Full-text available
Evidence-based guidelines for managing patients with intra-abdominal infection were prepared by an Expert Panel of the Surgical Infection Society and the Infectious Diseases Society of America. These updated guidelines replace those previously published in 2002 and 2003. The guidelines are intended for treating patients who either have these infections or may be at risk for them. New information, based on publications from the period 2003-2008, is incorporated into this guideline document. The panel has also added recommendations for managing intra-abdominal infection in children, particularly where such management differs from that of adults; for appendicitis in patients of all ages; and for necrotizing enterocolitis in neonates.
... There was no consensus on the choice and the duration of antibiotic therapy for appendicitis [5][6][7]. There were increasing numbers of prospective randomized control trial study on the use of single antibiotic in appendicitis in children [12][13][14][15]. These trials concluded that their choice of antibiotics was simpler and more cost-effective than the traditional one. ...
Article
Antibiotic resistance is a global issue especially in developed areas. With the emergence of antibiotic resistant-bacteria, the traditional choice of broad spectrum antibiotics may not be effective in complicated appendicitis. We herein report the bacteriology and antibiotic susceptibility of intra-operative peritoneal culture in children with acute appendicitis in Hong Kong. This may guide us to adjust the choice of antibiotics with evidence. A retrospective review of all cases of children who underwent laparoscopic appendicectomy from 2003 to 2007 was performed. Data including histology of appendixes, the choice of antibiotics, bacteriology, and antibiotic susceptibility of the intra-operative peritoneal cultures were analyzed. Over a 5-year period, 250 children were included in this study. 41 children had gangrenous- and 77 had ruptured appendicitis, respectively. Peritoneal swab was taken in 158 children. Common bacteria isolated including E. coli, Streptococcus, and Bacteroides. Ampicillin, cefuroxime, and metronidazole were our choice of antibiotics. 26% of children with gangrenous and 25% with ruptured appendicitis were insensitive to the current regime. Using 3 antibiotics regime by switching cefuroxime to ceftazidime, it covered 77% resistant bacteria. Using 4 antibiotics regime by adding gentamycin, it covered 96% resistant bacteria. One-fourth of children with gangrenous or ruptured appendicitis were insensitive to the current regime. This study provides evidence-based information on the choice of antibiotics.
... We have previously proven the equivalence of these two antibiotic regimens in children with perforated appendicitis. 10 Patients with penicillin allergies were treated with gentamicin and clindamycin alone. Antibiotics were started once the diagnosis of appendicitis was established, and were continued for up to 10 to 14 days until the white blood cells (WBC) and temperature had returned to within normal limits. ...
Article
There is persistent controversy regarding the optimal surgical therapy for children with appendicitis. We have recently adopted laparoscopic appendectomy in lieu of the open technique for children with perforated appendicitis. We hypothesized that laparoscopic appendectomy would be as effective as open appendectomy in preventing postoperative complications. We reviewed the medical records of children admitted to our hospital over a 5-year period with the diagnosis of perforated appendicitis. Patients were divided into two groups based on the operative approach: laparoscopic vs. open appendectomy. Demographic data, duration of presenting symptoms, initial white blood cell (WBC) count, length of stay, and complications were abstracted. Data were compared using appropriate statistical analyses. There was no difference between the laparoscopic (n = 43) and open (n = 77) groups with respect to gender, duration of presenting symptoms, initial WBC, or length of stay. However, patients in the laparoscopic group had a significantly lower complication rate than those in the open group (6/43 vs. 23/77, P = 0.05). Infectious complications were no different between groups. Patients in the laparoscopic group tended to be older than patients in the open group (10.6 +/- 3.3 years vs. 8.5 +/- 4.1 years, P = 0.003). Laparoscopic appendectomy for children with perforated appendicitis has the same infectious complication rate and a lower overall complication rate than open appendectomy. A prospective study with standardized postoperative care would be needed to determine whether laparoscopic appendectomy for children with perforated appendicitis is the treatment of choice, but until then it remains an attractive alternative.
... The impetus for defining a simplified postoperative antibiotic regimen is a strong one. Monotherapy with newer broad-spectrum agents such as piperacillin/tazobactum for intraabdominal infections has recently been demonstrated to be equally efficacious as traditional triple therapy [14,15]. Similarly, cefotaxime, a cephalosporin with a similar profile to ceftriaxone, has been shown to be equal to the aforementioned monotherapy schedule of piperacillin/tazobactum in children with complicated perforated appendicitis when combined with metronidazole [16]. ...
Article
Objective: Appendicitis is the most common abdominal emergency in children. When perforation is encountered, postoperative management is grounded upon the use of intravenous antibiotics. The 3-drug regimen of ampicillin, gentamicin, and clindamycin has long been the accepted standard by pediatric surgeons. Although effective and seemingly inexpensive, this regimen produces a cumbersome dosing schedule, which has inspired the search for a simpler regimen that does not compromise efficacy or expense. To this end, we have introduced a 2-drug regimen of ceftriaxone and Flagyl (Pharmacia Corporation, Chicago, Ill) with once-a-day dosing. Methods: A retrospective review was conducted of the most recent 250 patients treated at our institution with perforated appendicitis. Patients treated since the implementation of this 2-drug regimen were compared with the recent historical cohort treated with triple antibiotic coverage. Parameters analyzed between the 2 groups included temperature curves for the first 5 postoperative days, abscess rate, length of hospitalization, length of intravenous antibiotic treatment, and medication charges. Results: The 2-drug regimen was used in 57 patients (group 1) compared with 193 patients treated with triple antibiotic coverage (group 2). Maximum recorded temperature between the 2 groups was similar upon admission, but the mean maximum temperature in group 1 became significantly lower than group 2 from postoperative day 1 onward (P < .001). Postoperatively, an abscess developed in 8.8% of group 1 compared with 14.2% of group 2, which was not significantly different (P = .37). Mean length of stay was 6.8 days in group 1 and 7.8 days in group 2 (P = .03). Medication charges to the patient were 81.32 dollars per day in group 1 compared with 318.53 dollars per day in group 2, translating to 1186.05 dollars savings for 5 days. Conclusions: Once-a-day dosing with ceftriaxone and Flagyl provides adequate antibiotic coverage for the postoperative management of perforated appendicitis in children. This regimen allows patients to more rapidly defervesce compared with traditional triple antibiotic coverage; moreover, this simple regimen provides substantial advantages for administration and expense.
... Multiple drug therapy is a common therapeutic practice especially in patients with multiple complications (Nadler et al., 2003;Hemaiswarya and Doble, 2006). If two or more drugs with affinity for the same cytochrome P450 (CYP) enzyme are co-administered, their biotransformation may be compromised, leading to undesirable accumulation of the drugs with toxic side effects as possible consequence. ...
Article
Full-text available
Curcumin (diferuloylmethane) is a major yellow pigment and dietary component derived from Curcuma longa. It has potent anti-inflammatory, anticarcinogenic, antioxidant and chemoprotective activities among others. We studied the interactions of curcumin, a mixture of its decomposition products, and four of its individually identified decomposition products (vanillin, vanillic acid, ferulic aldehyde and ferulic acid) on five major human drug-metabolizing cytochrome P450s (CYPs). Curcumin inhibited CYP1A2 (IC(50), 40.0 microM), CYP3A4 (IC(50), 16.3 microM), CYP2D6 (IC(50), 50.3 microM), CYP2C9 (IC(50), 4.3 microM) and CYP2B6 (IC(50), 24.5 microM). Curcumin showed a competitive type of inhibition towards CYP1A2, CYP3A4 and CYP2B6, whereas a non-competitive type of inhibition was observed with respect to CYP2D6 and CYP2C9. The inhibitory activity towards CYP3A4, shown by curcumin may have implications for drug-drug interactions in the intestines, in case of high exposure of the intestines to curcumin upon oral administration. In spite of the significant inhibitory activities shown towards the major CYPs in vitro, it remains to be established, whether curcumin will cause significant drug-drug interactions in the liver, given the reported low systemic exposure of the liver to curcumin. The decomposition products of curcumin showed no significant inhibitory activities towards the CYPs investigated, and therefore, are not likely to cause drug-drug interactions at the level of CYPs.
Article
Background : Narrow-spectrum antibiotics have been found to be equivalent to anti-Pseudomonal agents in preventing organ space infections (OSI) in children with uncomplicated appendicitis. Comparative effectiveness data for children with complicated appendicitis remains limited. This investigation aimed to compare outcomes between the most common narrow-spectrum regimen (ceftriaxone with metronidazole: CM) and anti-Pseudomonal regimen (piperacillin/tazobactam: PT) used perioperatively in children with complicated appendicitis. Methods : Multicenter retrospective cohort study using clinical data from the NSQIP-Pediatric Appendectomy Collaborative database merged with antibiotic utilization data from the Pediatric Health Information System database. Mixed-effects multivariate regression was used to compare NSQIP-defined outcomes and resource utilization between treatment groups after adjusting for patient characteristics, disease severity, and clustering of outcomes within hospitals. Results : 654 patients from 14 hospitals were included, of which 37.9% received CM and 62.1% received PT. Following adjustment, patients in both groups had similar rates of OSI (CM: 13.3% vs. PT: 18.0%, OR 0.88 [95%CI 0.38, 2.03]), drainage procedures (CM: 8.9% vs. PT: 14.9%, OR 0.76 [95%CI 0.30, 1.92]), and postoperative imaging (CM: 19.8% vs. PT: 22.5%, OR 1.17 [95%CI 0.65, 2.12]). Treatment groups also had similar rates of 30-day cumulative post-operative length of stay (CM: 6.1 vs. PT: 6.0 days, RR 1.01 [95%CI 0.81, 1.25]) and hospital cost (CM: $19,235 vs. PT: $20,552, RR 0.92 [95%CI 0.69, 1.23]). Conclusions : Rates of organ space infection and resource utilization were similar in children with complicated appendicitis treated with ceftriaxone plus metronidazole and piperacillin/tazobactam.
Article
Background: Perforated appendicitis is the most common cause of intraabdominal abscess (IAA) in children. The optimal postoperative antibiotic regimen to reduce IAA has evolved in the last decade from triple-drug to 2-drug therapy (CM). Recent retrospective studies show decreased infectious complications with monotherapy PT. To date prospective comparative data are lacking. Therefore, a prospective randomized trial comparing PT versus CM was conducted. Methods: A multi-institutional prospective randomized trial was performed in children with perforated appendicitis comparing postoperative antibiotic regimens PT or CM. The primary outcome was 30-day postoperative IAA formation. Perforation was strictly defined as a hole in the appendix or fecalith in the abdomen, documented with intraoperative photographs. Results: One hundred sixty-two patients were enrolled during the study period. No differences in age, weight, or duration of presenting symptoms were identified. In addition, length of stay, duration of intravenous antibiotic treatment, discharge oral antibiotic treatment, and antibiotic-related complications did not differ between groups. Compared to the CM group, the PT group had significantly lower IAA rate [6.1% vs 23.8%, odd ratio (OR) 4.80, P = 0.002], lower postoperative computed tomography imaging rate (13.9% vs 29.3%, OR 2.57, P = 0.030), and fewer emergency room visits (8.8% vs 26.4%, OR 3.73, P = 0.022). Multivariate logistic regression analysis found the use of CM versus PT (OR 9.21, P = 0.021) to be the most significant predictor for developing IAA. Conclusions: In children with perforated appendicitis, postoperative monotherapy with PT is superior to standard 2-drug therapy with CM and does not increase antibiotic-related complications or antibiotic exposure duration.
Article
Background ‘Fast‐track’ surgery protocols aim to standardize and rationalize post‐operative care, with evidence of safety and efficacy in both uncomplicated and complicated childhood appendicitis. Generalization for broader adoption has been limited by variation in protocol design, including specific antibiotic choice, discharge criteria, post‐operative monitoring and patient selection. Methods A systematic review of the literature was performed to evaluate the current evidence underpinning fast‐track protocols for childhood appendicitis and identify areas of consensus and controversy. Results About 33 studies met the inclusion criteria, including four prospective observational studies, 20 case–control studies, seven cohort studies and two randomized controlled trials studying uncomplicated (n = 9), complicated (n = 18) and mixed cohorts (n = 6). Reduction in length of hospital stay was almost universally reported, with equivalent or improved complication rates. Key themes of protocols included antibiotic choice and duration, discharge criteria and post‐operative laboratory and radiographic testing. Rationalized analgesia is an underexplored aspect of protocol design, and a standardized definition of complicated appendicitis remains elusive. Conclusion Standardized care of childhood appendicitis has been shown to be safe and effective in several local and international centres. Next steps include investigation of a complicated appendicitis protocol that integrates rationalized analgesia in appendicectomy recovery, and development of a consistent classification scheme for complicated disease to aid in identification of amenable cohorts.
Chapter
Reifung und Wachstum haben spezifische Auswirkungen auf die Pharmakokinetik (PK) und Pharmakodynamik (PD) und damit auf die Wirksamkeit und Sicherheit von Arzneimitteln im Kindesalter. Die eingeschränkte Verfügbarkeit verlässlicher Studiendaten bei Kindern erschwert die Pharmakotherapie in dieser Population, insbesondere bei off-label use oder unlicensed use. Die wichtigsten Aspekte der Pharmakotherapie sind die Wahl des Arzneimittels für die Indikation, die Dosierung, die Anwendungsdauer und die Verabreichungsform. Dosierungen können indikationsspezifisch sein und müssen an die Altersgruppe und ggf. bei Grunderkrankungen an die Komedikation oder Organdysfunktionen angepasst werden. Gerade für die antibiotische Therapie existieren weitere PKPD-Zielparameter, abhängig von der Art des Antibiotikums, die Einfluss auf die Dosierung und das Verabreichungsschema haben. Die Dauer der Pharmakotherapie ergibt sich aus der Indikation und soll bei akuten Erkrankungen in aller Regel begrenzt sein.
Article
Ethno-pharmacological relevance: Hyptis suaveolens (L) Poit and Boerhavia diffusa Linn are medicinal herbal plants commonly found in the tropics and sub-tropics. They are used to treat various conditions among them boils, dyslipidaemia, eczema, malaria, jaundice and gonorrhoea. Thus, the herbal medicinal extracts are now found as part of some commercial herbal formulations. There has not been adequate characterisation of these medicinal herbs on their effects on drug metabolising enzymes. Aim of the study: To investigate the effects of extracts of Hyptis suaveolens (HS) and Boerhavia diffusa (BD) on activity of drug metabolizing enzymes, CYP1A2, CYP2D6 and CYP3A4, as well predict their potential for herb-drug interaction. A secondary aim was to identify constituent compounds such as polyphenolics, in the crude extract preparations of Hyptis suaveolens and Boerhavia diffusa and measure them for activity. Materials and methods: CYP450 inhibition assays using recombinant CYP450 (rCYP) and fluorescence screening employing individual isozymes (CYP1A2, CYP2D6 and CYP3A4) were used to determine reversible- and time-dependent inhibition (TDI) profiles of extracts of Hyptis suaveolens and Boerhavia diffusa. Inhibition kinetic parameters, Ki and Kinact were also estimated. UPLC-MS employing a Synapt G2 (ESI negative) coupled to a PDA detector was used to identify polyphenolic compounds in crude extracts of Hyptis suaveolens and Boerhavia diffusa. Results: The inhibitory potency of Hyptis suaveolens and Boerhavia diffusa extracts varied among the different enzymes, with CYP1A2 (3.68 ± 0.10µg/mL) being the least inhibited by HS compared to CYP2D6 (1.39 ± 0.01µg/mL) and CYP3A4 (2.36 ± 0.57µg/mL). BD was most potent on CYP3A4 (7.36 ± 0.94µg/mL) compared to both CYP2D6 (17.79 ± 1.02µg/mL) and CYP1A2 (9.48 ± 0.78µg/mL). Extracts of Hyptis suaveolens and Boerhavia diffusa exhibited TDIs on all CYPs. The most prominent phenolic candidates identified in both medicinal herbs using UPLC-MS analysis included caffeic acid, rutin, quercetin, citric acid, ferulic acid and gluconic acid. These phenolic compounds are thought to potentially give HS and BD their therapeutic effects and inhibitory characteristics affecting CYP450 activities. In vivo predictions showed the potential for HS and BD extracts to cause significant interactions if co-administered with other medications. Conclusions: The study reveals that crude aqueous extracts of HS and BD potentially inhibit drug metabolising isozymes CYP1A2, CYP2D6 and CYP3A4 in a reversible and time-dependent manner. Thus care should be taken when these extracts are co-administered with drugs that are substrates of CYP1A2, CYP2D6 and CYP3A4.
Article
Background: Although it is accepted that complicated appendicitis requires antibiotic therapy to prevent post-operative surgical infections, consensus protocols on the duration and regimens of treatment are not well established. This study aimed to compare the outcome of post-operative infectious complications in patients receiving old non-standardized and new standard antibiotic protocols, involving either 5 or 10 days of treatment, respectively. Methods: We enrolled 1,343 patients who underwent laparoscopic surgery for complicated appendicitis between January 2009 and December 2014. At the beginning of the new protocol, the patients were divided into two groups; 10 days of various antibiotic regimens (between January 2009 and June 2012, called the non-standardized protocol; n = 730) and five days of cefuroxime and metronidazole regimen (between July 2012 and December 2014; standardized protocol; n = 613). We compared the clinical outcomes, including surgical site infection (SSI) (superficial and deep organ/space infections) in the two groups. Results: The standardized protocol group had a slightly shorter operative time (67 vs. 69 min), a shorter hospital stay (5 vs. 5.4 d), and lower medical cost (US$1,564 vs. US$1,654). Otherwise, there was no difference between the groups. No differences were found in the non-standardized and standard protocol groups with regard to the rate of superficial infection (10.3% vs. 12.7%; p = 0.488) or deep organ/space infection (2.3% vs. 2.1%; p = 0.797). Conclusions: In patients undergoing laparoscopic surgery for complicated appendicitis, five days of cefuroxime and metronidazole did not lead to more SSIs, and it decreased the medical costs compared with non-standardized antibiotic regimens.
Article
Objective: To compare treatment failure leading to hospital readmission in children with complicated appendicitis who received oral versus intravenous antibiotics after discharge. Background: Antibiotics are often employed after discharge to prevent treatment failure in children with complicated appendicitis, although existing studies comparing intravenous and oral antibiotics for this purpose are limited. Methods: We identified all patients aged 3 to 18 years undergoing appendectomy for complicated appendicitis, who received postdischarge antibiotics at 35 childrens hospitals from 2009 to 2012. Discharge codes were used to identify study subjects from the Pediatric Health Information System database, and chart review confirmed eligibility, treatment assignment, and outcomes. Exposure status was based on outpatient antibiotic therapy, and analysis used optimal and full matching methods to adjust for demographic and clinical characteristics. Treatment failure (defined as an organ-space infection) requiring inpatient readmission was the primary outcome. Secondary outcomes included revisits from any cause to either the inpatient or emergency department setting. Results: In all, 4579 patients were included (median: 99/hospital), and utilization of intravenous antibiotics after discharge ranged from 0% to 91.7% across hospitals. In the matched analysis, the rate of treatment failure was significantly higher for the intravenous group than the oral group [odds ratio (OR) 1.74, 95% confidence interval (CI) 1.05-2.88; risk difference: 4.0%, 95% CI 0.4-7.6%], as was the rate of all-cause revisits (OR 2.11, 95% CI 1.44-3.11; risk difference: 9.4%, 95% CI 4.7-14.2%). The rate of peripherally inserted central catheter line complications was 3.2% in the intravenous group, and drug reactions were rare in both groups (intravenous: 0.7%, oral: 0.5%). Conclusions: Compared with oral antibiotics, use of intravenous antibiotics after discharge in children with complicated appendicitis was associated with higher rates of both treatment failure and all-cause hospital revisits.
Article
Full-text available
Recent data suggest that monotherapy with a broad-spectrum antibiotic may be as efficacious as, and potentially less costly than, standard multi-drug therapy. We compared mono-therapy with intravenous piperacillin-tazobactam (PT) with multi-drug therapy with cefotaxime and metronidazole (CM) in aspect of postoperative complications and hospital stay.
Chapter
Full-text available
Appendicitis is one of the most common pathologies in children. Laparoscopic appendectomy is now a frequently performed procedure and is probably the easiest laparoscopic therapeutic procedure to start with for training surgeons. Nevertheless its application remains controversial (Canty et al. 2000; Emil et al. 2003; Garbutt et al. 1999; Hermann and Otte 1997; Steyaert et al. 1999). The reasons for this are the good results obtained with standard open appendectomy and the fact that most appendectomies are performed during duty hours when not enough experience may be available. Conversely laparoscopy for right iliac fossa pain has an unquestionable diagnostic benefit, particularly in girls. Preoperative ultrasonography, however, is become more and more accurate in confirming or excluding appendicitis (Dilley et al. 2001). There are three different techniques of laparoscopic appendectomy: the "out" technique (Fig. 47.1), the "mixed in-out" technique (Fig. 47.2), and the "in" technique (Fig. 47.3). All three techniques will be described.
Article
Full-text available
Background: The primary objective of this study was to compare triple therapy with ertapenem treatments in pediatric patients with perforated appendicitis, especially in terms of postoperative infectious complications. The secondary objective of this study was to assess the relative impact of therapy with ertapenem and triple antibiotic regimen on the emergence of resistant bacteria in bowel flora in the patients. Materials and methods: Children aged 3 months to 17 years with perforated appendicitis were randomized 1:1 to receive ertapenem or triple therapy. Serial rectal cultures were obtained from participants enrolled in the study, allowing assessment of the relative impact of therapy with ertapenem and triple therapy on bowel colonization by resistant bacteria. Results: In this study, 107 patients were included. No difference existed in time to full oral intake and regular diet, the length of antibiotic therapy, the length of the postoperative hospitalization, or the length of hospital stay between the two groups. Patients in the triple-therapy group were more likely to suffer from a postoperative infectious complication than those in the ertapenem group (6/54 vs. 2/53, p > 0.05). Bowel colonization with resistant organisms at the end of therapy in the triple-therapy group was significantly different than in the ertapenem group (35.2 vs. 11.3%, p < 0.05). Conclusions: Bowel colonization with resistant bacteria was less likely to occur after ertapenem treatment than triple therapy. The results of this trial suggest that ertapenem may be a useful option that could eliminate the need for combination and/or multidosed antibiotic regimens for the empiric treatment of perforated appendicitis in children.
Article
SUMMARY Background: Wound infection is one of the most common complications of appendectomy. We devised a method for early detection of this complication. A piece of braid suture is left in the subcutaneous tissue (sentinel stitch) of the operative wound, is withdrawn 24 to 48 after the surgical procedure and cultured. Aim: To assess the usefulness of the sentinel stitch in the diagnosis of wound infections. Material and Methods: Forty six patients operated for a perforated acute appendicitis were studied. The cultures of the sentinel stitch were compared with the clinical evaluation of the operative wound, indicating the presence of infection. Results: Eleven patients had an operative wound infection. Ten of these had a positive culture of the sentinel stitch. The cultures were negative in 34 of 36 patients without wound infection. Therefore, the sensitivity and specificity of the sentinel stitch were 91 and 97% respectively. Conclusions: The sentinel stitch is a simple and effective method for the early detection of wound infections after appendectomy.
Article
Appendicitis remains the most common cause of acute abdominal surgical disease in children (1-3). The treatment of acute appendicitis engenders very little controversy; appendectomy has been the accepted treatment of choice for over 100 years, with excellent results. However, once the appendix has perforated, the potential morbidity increases, along with controversy regarding its treatment. Children, especially those under 8 years of age are more likely to present with perforated appendicitis than adults (4). Despite the commonality of ruptured appendicitis in children, there is no treatment consensus. This chapter discusses the current diagnostic tools and therapeutic approaches to complications of appendicitis in children, as well as controversies in management.
Article
Objective - To review evidence-based data regarding the use of antibiotics for the treatment of appendicitis in children. Methods - A literature search using “appendicitis” and “antibiotics” as key words and restricting target population to children (0-18) was carried out. Selected studies were analyzed to find answers to the following questions: 1) Should perioperative antibiotics be used for paediatric patients with nonperforated appendicitis? 2) Which perioperative antibiotic should be chosen? 3) Is it possible to treat children with nonperforated appendicitis with antibiotics solely? 4) For patients with perforated appendicitis treated with appendicectomy: a) Which intravenous antibiotics should be used? b) How long should intravenous antibiotics be used? c) Is it possible to shift to oral drugs? Results - Children with nonperforated appendicitis must receive preoperative, broad-spectrum antibiotics, even if there is no univocal evidence about which regimen is the best. The sole use of antibiotics is not identified as an alternative to appendectomy in the management of acute appendicitis. In children with perforated appendicitis who had undergone appendicectomy, intravenous broad-spectrum, single, or double agent antibiotics is as equally efficacious as triple agent therapy. However, if intravenous antibiotics are administered properly, oral antibiotics are not necessary, but they could be administered to complete a total antibiotic course of 7 days. Intravenous therapy should be continued until the patient is afebrile and symptoms have resolved completely. Conclusions - Current evidence supports using guidelines in the paediatric population for the antibiotic
Article
Background: To prevent surgical site infection (SSI) after appendectomy, antibiotic prophylaxis has been recommended for all patients, but this approach is based largely on bacteriologic findings that are decades old. The objective of this study was to reevaluate the bacteriology of acute appendicitis in order to assess the usefulness of current antibiotic prophylaxis. Methods: Between January 1 and December 31, 2010, 117 patients with pathology-proved acute appendicitis were recruited. Antibiotic prophylaxis was given according to national guidelines. Immediately after operation, the luminal contents of the appendices were swabbed for bacterial culture. The charts of the patients were surveyed retrospectively for postoperative complications until June 30, 2011. Results: Bacteria were isolated from 115 of 117 specimens sent for culture (98%). Of the 115 samples that yielded bacteria, all gave rise to aerobic isolates and five yielded mixed aerobic and anaerobic isolates. The most common aerobic organism was Escherichia coli, which was present in 100 of 117 patients who had pathology-proved acute appendicitis (85%). Less frequent organisms were Klebsiella pneumoniae (30 cases; 26%), Streptococcus spp. (29 cases; 25%), Enterococcus spp. (21 cases; 18%), and Pseudomonas aeruginosa (18 cases; 15%). All P. aeruginosa isolates were sensitive to amikacin, ceftazidime, and cefepime; but seven of the eight were resistant to cefuroxime. Eight patients were identified as having had a postoperative SSI, and P. aeruginosa was isolated from five of these cases. The isolation of P. aeruginosa correlated significantly with SSI (p=0.002). Conclusions: The most commonly identified aerobic bacteria associated with acute appendicitis were E. coli, followed by K. pneumoniae, Streptococcus, Enterococcus, and P. aeruginosa. Pseudomonas aeruginosa frequently was not covered by the prophylactic antibiotics chosen and might be associated with SSI.
Article
Multiresistant bacterial strains tend to develop, especially enterobacteriacae, in intraabdominal infections. The aim of this study was to characterize the evolution of the bacterial biota in complicated appendicitis in children over the past 20 years and their acquired resistance rates to antibiotics. All pediatric patients admitted in the emergency unit for complicated appendicitis were retrospectively reviewed during 3 periods: 1989 to 1991, 1999 to 2000, and 2009 to 2010. Results of peritoneal swabs were analyzed regarding bacterial species and resistance to antibiotics. Statistical significance was set at P < .05. Thirty-four, 48, and 85 patients from the 3 periods, respectively, were included, with 1 to 6 bacterial strains found in each peritoneal sample. During the first period, 80% of the biota was composed of enterobacteriacae and anaerobes and then decreased to 65%, whereas streptococci levels increased from 0 to 22%. Pansusceptibility rates remained stable (17%, 16.8%, and 15.6% for the 3 periods, respectively). Piperacillin, vancomycin, ticarcillin-clavulanic acid, and fluoroquinolones were associated with increased resistance rates, unlike antibiotic associations currently used as postoperative treatments. No significant increase in resistance rates of bacteriacae in complicated appendicitis in children was found over the last 20 years. Empirical antibiotherapy protocols currently recommended remain efficient on this particular biota.
Chapter
Acute appendicitis is the most common abdominal surgical emergency. Careful history taking and focused physical examination are essential for accurate diagnosis. CT scan has become a routine adjunct in the work-up and is particularly helpful in female patients and in patients with atypical presentation. Prompt operative management with perioperative antibiotic prophylaxis is the mainstay of treatment. Open and laparoscopic appendectomy are associated with low morbidity and mortality. The laparoscopic approach is associated with lower wound infection rate and shorter hospital stays despite longer operative time and higher costs. Delay in presentation, diagnosis or treatment of acute appendicitis is associated with increased risk of perforation resulting in higher infectious complications. Patients presenting with perforated appendicitis with a phlegmon or abscess can be managed with immediate appendectomy or non-operatively with antibiotics, bowel rest and percutaneous drainage, followed by either expectant management or interval appendectomy. Although immediate appendectomy is feasible, it can be technically challenging and is associated with a higher incidence of complications than conservative management.
Article
Piperacillin-tazobactam (PIP/TAZO) has been extensively used in adults with nosocomial infections and with fever and neutropenia. The available data considering the use of PIP/TAZO have not been reviewed in detail. Review discussing the use of PIP/TAZO in neonatal and paediatric patients. Medline search focusing on articles published in English. Owing to the paucity of randomized controlled trails, uncontrolled studies and case series were included. PIP/TAZO may safely be used in paediatric patients as an empiric treatment for serious infections in hospital environments where resistance to common first-line antimicrobials has emerged. The most common indications in paediatric patients are nosocomial infections owing to resistant Gram-negatives, exacerbation of pulmonary colonization with Psuedomonas aeruginosa in patients with cystic fibrosis, intra-abdominal infections, fever and neutropenia in paediatric cancer patients. The influence of PIP/TAZO routine use on the selection of extended-spectrum beta-lactamase producing Gram-negatives and on the prevalence of vancomycin-resistant enterococci is still a matter of debate. In particular the use of PIP/TAZO in neonates and PIP/TAZO monotherapy in paediatric cancer patients with fever and neutropenia should be investigated in prospective randomized studies including a sufficient number of patients.
Article
Initial non-operative therapy for children with perforated appendicitis has become increasingly popular with the advent of powerful broad-spectrum antibiotics. However, there is no consensus regarding which patients may be managed effectively with this strategy. We reviewed all children with perforated appendicitis who were treated initially with non-operative therapy to determine those characteristics that may predict a successful outcome. We reviewed the medical records of children admitted to our hospital between January 1, 2000 and May 1, 2003 with the diagnosis of perforated appendicitis. Only those who were treated initially with a single broad-spectrum antibiotic (piperacillin-tazobactam), with the intention of performing an interval appendectomy, were included in this study. Patients were divided into two groups based on whether they were managed successfully with non-operative therapy: Responders and non-responders. Non-responders were defined as patients who either did not improve with antibiotic therapy or who required appendectomy prior to their electively scheduled time (six weeks). Demographic data, duration and type of presenting symptoms, initial white blood cell count (WBC), percent bands, percent neutrophils (PMNs), computed tomography (CT) interpretation, and interventions/operations were abstracted. Categorical data were compared using Chi-square analysis or the Fisher exact test; continuous variables were compared using the Student t-test and the Mann-Whitney U-test. Overall, 26% (19/73) of patients treated initially non-operatively required appendectomy prior to the electively scheduled date. There was no difference between responders (n = 54) and non-responders (n = 19) with respect to age, gender, initial WBC, percent bands, percent PMNs, or duration and type of presenting symptoms. However, responders were more likely to have a phlegmon on CT scan compared to non-responders (11/54 vs. 0/19, p = 0.03). Non-responders were twice as likely to undergo drainage of an abscess by interventional radiology (10/19 vs. 13/54, p = 0.02) compared to responders. Among all patients who required percutaneous drainage, the failure rate of non-operative management was 43% (10/23). Children with perforated appendicitis can be managed effectively with nonoperative therapy, even in the presence of intra-abdominal abscesses. However, the need for abscess drainage increases the failure rate, perhaps due to inadequate source control. Those patients with a phlegmon on CT scan as opposed to an abscess, are most likely to respond to non-operative management. Initial non-operative therapy of perforated appendicitis in children is appropriate under certain clinical circumstances, especially when the body itself or interventional radiology can achieve adequate source control.
Article
We conducted a retrospective cohort study to compare the use of triple therapy versus monotherapy for children and adolescents with perforated appendicitis and to determine whether there has been a transition to monotherapy within the freestanding children's hospitals that contribute to the Pediatric Health Information System database. We used the Pediatric Health Information System database, which includes billing and discharge data for 32 children's hospitals in the United States, to examine the trend in antibiotic usage and whether the postappendectomy antibiotic regimen was associated with differences in complication-related readmissions, length of stay, or charges in a population of children and adolescents with ruptured appendicitis and discharge dates between March 1, 1999, and September 30, 2004. Pairwise regression analyses were performed to compare the most common monotherapy regimens with the triple therapy. A total of 8545 patients met the inclusion criteria, of whom 58%, over the entire study period, received the aminoglycoside-based triple antibiotic therapy on postoperative day 1. There was, however, a notable transition over this 6-year period, from 69% to 52% of surgeons using aminoglycoside-based combination therapy. There were no significant differences in the odds of readmission at 30 days except for the group receiving ceftriaxone, which was associated with significantly decreased odds. The subgroup receiving piperacillin/tazobactam monotherapy demonstrated significantly decreased length of stay (-0.90 days) and total hospital charges, and the group receiving cefoxitin demonstrated significantly decreased length of stay (-1.89 days), as well as decreased pharmacy and total hospital charges. Single-agent antibiotic therapy in the treatment of perforated appendicitis is being used with increasing frequency, is at least equal in efficacy to the traditional aminoglycoside-based combination therapy, and may offer improvements in terms of length of stay, pharmacy charges, and hospital charges.
Article
Full-text available
The Surgical Infection Society last published guidelines on antimicrobial therapy for intra-abdominal infections in 1992 (Bohnen JMA, et al., Arch Surg 1992;127:83-89). Since then, an appreciable body of literature has been published on this subject. Therefore, the Therapeutics Agents Committee of the Society undertook an effort to update the previous guidelines, primarily using data published over the past decade. An additional goal of the Committee was to characterize its recommendations according to contemporary principles of evidence-based medicine. To develop these guidelines, the Committee carried out a systematic search for all English language articles published between 1990 and 2000 related to antimicrobial therapy for intra-abdominal infections. This literature was reviewed individually and collectively by the Committee, and categorized according to the type of study and its quality. Additional articles published prior to 1990 were also utilized when necessary. By a process of iterative consensus, the Committee developed provisional guidelines for antimicrobial therapy for intra-abdominal infections based on this evidence. Following extensive review by members of the Society, these guidelines were approved for publication in final form by the Council of the Surgical Infection Society. This executive summary delineates the Society's current recommendations for antimicrobial therapy of patients with intra-abdominal infections. Topics discussed include the selection of patients needing therapeutic antimicrobials, duration of antimicrobial therapy, acceptable antimicrobial regimens, and identification and treatment of higher-risk patients. Guidelines for patient selection and specific antimicrobial regimens were based on relatively good evidence, but those regarding optimal duration of therapy and treatment of higher-risk patients relied mostly on expert opinion, since there was a paucity of high-quality studies on those issues. Relevant areas for future investigation include the safety, convenience, and cost-effectiveness of available antimicrobial regimens for lower-risk patients, and better means for identifying and treating higher-risk patients with intra-abdominal infections.
Article
Perforated appendicitis in children continues to be associated with significant morbidity. In 1976, a treatment algorithm was begun at the authors' institution, which included immediate appendectomy, antibiotic irrigation of the peritoneal cavity, transperitoneal drainage through the wound, and 10-day treatment with intravenous ampicillin, clindamycin, and gentamicin. Initial results with this scheme in 143 patients demonstrated a 7.7% incidence of major complications and no deaths. From 1981 through 1991, the authors continued to use this treatment plan in all patients with perforated appendicitis. Three hundred seventy-three patients with perforated appendicitis were treated, and the rate of major complications was 6.4%. Infectious complications occurred in 18 patients (4.8%) and included intraabdominal abscesses (5 patients, 1.3%), phlegmon treated with an extended course of antibiotics (6 patients, 1.6%), wound infections (5 patients, 1.3%), and enterocutaneous fistula requiring further operations (2 patients, 0.5%). There were six cases of small bowel obstruction (1.6%), which required operative intervention. There were no deaths. The average length of stay for all patients was 11.4 days (range, 8 to 66 days). Utilization of transperitoneal drainage and choice of antibiotic therapy continue to be sources of controversy in the surgical literature. However, the treatment plan used in the present study resulted in the lowest complication rate reported to date, and the authors conclude that this scheme is truly the "gold standard" for treatment of perforated appendicitis. New treatment plans using laparoscopic appendectomy, different or shorter courses of antibiotics, or not using drains should have complication rates that are as low as, or lower than this one to be considered as useful alternatives.
Article
During the 2-year period from January 1, 1987 to December 31, 1988, 656 emergency appendectomies were performed on the Pediatric Surgery Service at the Los Angeles County-USC Medical Center. Of these, 398 patients were 12 years of age or less, and 227 appendices (57%) were perforated or gangrenous. The records of 167 of those patients with perforated or gangrenous appendices, treated by a standardized protocol are summarized. The protocol included perioperative antibiotics of gentamicin and clindamycin, appendectomy through a muscle-splitting incision, irrigation of the peritoneal cavity with saline, and peritoneal drainage through the lateral aspect of the wound with skin closure. There was no mortality, and the major complication rate was 8%, with 3% developing intraabdominal abscesses and 5% with bowel obstructions. The minor complication rate was 11%, and included prolonged ileus and prolonged fever, with no wound infections. The average hospital stay was 8.7 days. Our experience suggests that the adopted protocol is reliable for preventing wound infections without increasing the rate of intraabdominal abscesses in an innercity population with particularly advanced stages of appendicitis.
Article
Controversy persists in the management of perforated appendicitis with regard to antibiotic choice and duration, operative timing, drain utilization, and wound closure. For 2 decades at the authors' institution, patients were treated with ampicillin, gentamicin, and clindamycin for 10 inpatient days, with drains in the abdomen, resulting in lower complication rates than most other published series. Managed care pressures have led to less aggressive medical management regimens with length of stay and financial factors viewed as principal outcome measures with little emphasis on clinical outcomes. In addition, there are little prospective data on clinical outcomes. The authors sought to determine whether our previously documented excellent quality outcomes could be maintained when modifications aimed at decreasing cost and length of stay in our protocol were instituted. The authors monitored prospectively clinical outcomes in patients with perforated appendicitis treated according to their clinical practice guidelines over a 43-month period. Patients received a single antibiotic, piperacillin-tazobactam, intravenously for 10 days. They were permitted to go home with a percutaneous intravenous catheter for the final 5 days if medical and social criteria were met. Other practices from our earlier protocol were continued, including immediate operation, placement of Penrose drains, and primary wound closure. Of 150 patients treated on our protocol, major complications included intraabdominal abscess in 5 (3.3%), cecal fistula in 2 (1.3%), phlegmon in 3 (2.0%), wound infection in 4 (2.7%), and no small bowel obstructions requiring operation. None of these complications, nor their aggregate, were significantly more common than those reported in 373 patients treated over 11 years on the authors' prior protocol (chi2, P > .05). Prospective outcome analysis of our protocol shows that a single broad-spectrum antibiotic (allowing portions of therapy to be delivered less expensively on an outpatient basis) effectively can treat postoperative appendicitis with very few infectious complications. These outcome data provide baseline against which future protocols can be compared. All treatment modifications aimed at decreasing costs must be analyzed to ensure quality of care is not unduly compromised.
Article
The proper duration of postoperative intravenous (IV) antibiotics in patients suffering complicated (perforated or gangrenous) appendicitis is debatable. Some advocate a set minimum number of IV antibiotic days whereas others discontinue IV antibiotics depending on the patient's clinical course regardless of the length of therapy. Our objective was to determine whether there are differences in morbidity and resource utilization between the two treatment methodologies. Ninety-four patients with intraoperative findings of complicated appendicitis were included. In all patients IV antibiotics were discontinued on the basis of clinical factors. However, Group 1 patients were given a minimum 5-day IV antibiotic course whereas Group 2 patients had no minimum IV antibiotic requirement. Group 1 patients received more IV antibiotics than Group 2 patients did (5.9 vs 4.3 days; P = 0.014). Infectious complications were not statistically different between the two groups (13.0% in Group 1 and 12.5% in Group 2). Average hospital stay was also not statistically different between the two groups. The data suggest that a protocol with no minimum IV antibiotic requirement in patients with complicated appendicitis does not increase morbidity. Furthermore, the protocol arm with no minimum IV antibiotic requirement led to less IV antibiotic use but did not significantly decrease hospital stay.
Article
For children with perforated appendicitis, the use of a prolonged course of intravenous (i.v.) antibiotics is equivalent to a short course of i.v. antibiotics followed by sequential conversion to oral (PO) antibiotics. Prospective, randomized, clinical trial. Multicenter study in tertiary children's hospitals. Children (aged 5-18 years) with perforated appendicitis found at laparotomy. Children were randomized after appendectomy either to a 10-day course of a combination of i.v. ampicillin, gentamicin sulfate, and clindamycin (n = 10); or to a short course of a combination of i.v. ampicillin, gentamicin, and clindamycin, followed by conversion to a combination of p.o. amoxicillin and clavulanate potassium plus metronidazole (n = 16). The primary outcome measure was clinical success, which was rated as complete, partial, or failure. Secondary outcome measures included return of oral intake, duration of fever, return of normal white blood cell count, and patient charges. Treatment equivalence was determined using confidence interval analysis. We found treatment equivalence between the i.v. and i.v./p.o. groups, with 6 (60%) complete and 4 (40%) partial successes for the 10 patients in the i.v. group and 15 (94%) complete and 1 (6%) partial successes for the 16 patients in the i.v./p.o. group (P< or =.05). There was no difference in return of oral intake, duration of fever, or return of normal white blood cell count between the groups. Conversion to oral therapy results in savings of approximately $1500 per case. There is treatment equivalence between prolonged i.v. therapy and i.v. therapy followed by conversion to oral antibiotic therapy in children with perforated appendicitis.
Article
After appendectomy for perforated appendicitis children have traditionally been managed with intravenous broad-spectrum antibiotics for 5 to 10 days and then until fever and leukocytosis have resolved. We prospectively evaluated a protocol of hospital discharge on oral antibiotics when oral intake is tolerated-regardless of fever or leukocytosis-in a consecutive series of 80 children between one and 15 years of age who underwent appendectomy (38 open and 42 laparoscopic) for perforated appendicitis. At discharge subjects began a 7-day course of oral trimethoprim/sulfamethoxazole and metronidazole. Patients were discharged between 2 and 18 days postoperatively (mean 5.3 days). Sixty-six were discharged on oral antibiotics, and 28 of these had persistent fever or leukocytosis. Two patients (2.5%) developed postoperative intra-abdominal abscesses while inpatients. Wound infections developed in seven patients (8.8%) four of whom were on intravenous antibiotics. Among the 66 children who were discharged on oral antibiotics without having had an inpatient infectious complication there were three wound infections (4.4%). None of these patients had a fever or leukocytosis at discharge. We conclude that after appendectomy for perforated appendicitis children may be safely discharged home on oral antibiotics when enteral intake is tolerated regardless of fever or leukocytosis.
Article
The treatment of perforated appendicitis in children often involves a combination of surgical and medical therapy. The aim of this study was to document the degree of consensus in the current management of perforated appendicitis in children. A survey was sent to all practicing pediatric surgeons in North America in April 2000 who were members of the American Pediatric Surgical Association for 1999-2000. Survey questions pertained to preoperative, perioperative, and postoperative practice patterns, particularly those issues related to use of antibiotic therapy. Among eligible surgeons, 80.2% completed the survey. Although more than 80% of respondents practiced in an academic setting, only 17% of surgeons used a formal clinical practice guideline to direct care. Responses varied substantially in the duration of postoperative antibiotic therapy, the use of intravenous or oral agents or both, and the duration of hospitalization. A considerable number of patients are receiving a portion of their intravenous antibiotic therapy as outpatients. There is little apparent consensus in the many aspects of perioperative and postoperative care of perforated appendicitis in children across North America. Only a fraction of surgeons currently uses a formal clinical practice guideline for treatment of perforated appendicitis, although increased pressures to develop more cost-effective therapeutic strategies can encourage development of additional guidelines. Definitive evidence to inform development of such guidelines and enhance consensus is lacking. Further studies are needed across institutions to better inform clinical decisions in light of a changing practice environment and treatment alternatives.
Article
To improve clinical results and resource utilization in the care of appendicitis in children, the authors examined the current practice and outcomes of 30 pediatric hospitals. The Pediatric Health Information System (PHIS) database consists of comparative data from 30 free-standing Children's hospitals. The study population of 3,393 children was derived from the database by selecting the "Diagnosis Related Group Code" for appendicitis (APRDRGv12 164), ages 0 to 17 years, using discharges between October 1, 1999 and September 30, 2000. Data are expressed as the range and median for individual hospital outcomes. The nonpositive appendectomy rate ranged from 0 to 17% at the 30 hospitals (median, 2.6%). Ruptured appendicitis varied from 20% to 76% (median, 36.5%). The median length of stay (LOS) for nonruptured appendicitis was 2 days (range, 1.4 to 3.1 days), ruptured appendicitis varied from 4.4 to 11 days (median, 6 days). The median readmission rate within 14 days was 4.3% (0 to 10%). Laparoscopic appendectomy varied from 0 to 95% in the 30 hospitals (mean, 31%) The LOS did not vary significantly in laparoscopic versus open for nonruptured (2.3 v 2.0 days) or ruptured appendicitis (5.5 v 6.2 days). Days on antibiotics for ruptured appendicitis ranged from 4.6 to 7.9 days (median, 5.9 days) Children receiving any study varied from 18% to 89% (median, 69%). Ultrasound scan and computed tomography (CT) were comparable in both nonruptured (13% ultrasound scan v 14%) and ruptured appendicitis (14% ultrasound scan v 21% CT). Significant variability in practice patterns and resource utilization exists in the management of acute appendicitis in pediatric hospitals. Clinical outcomes could be improved by collaborative initiatives to adopt evidence-based best practices.