Content uploaded by çetin ali karadağ
Author content
All content in this area was uploaded by çetin ali karadağ on Sep 28, 2015
Content may be subject to copyright.
Ertapenem versus Standard Triple Antibiotic Therapy for the Treatment of Perforated Appendicitis in Pediatric Patients: A Prospective Randomized Trial
Abstract
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.
... We identified 2,102 articles in the databases searched. After removing duplications and non-eligible articles, 15 articles were included in the present study ( Figure 1 and Table 1) (6,(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). ...
... Two out of 8 RCTs, were rated as having a high risk of bias due to non-blinding of participants and personnel, and potential conflict of interest, such as commercial funding (31,33). The other 6 studies were rated as having moderate risk of bias due to moderate risk of non-blinding outcome assessment, high attrition rate or selective reporting (6,32,(34)(35)(36)(37). ...
... In studies comparing outcomes for patients receiving ertapenem, single or combination therapy, vs. other drugs, 8 studies reported treatment success rates (6,(34)(35)(36)(37)(40)(41)(42), 9 studies reported on length of stay (31-33, 35, 36, 39, 40, 42, 44), and 2 studies reported on mortality rates (6,37). Twelve studies (6,(31)(32)(33)(34)(35)(36)(37)(38)(40)(41)(42) reported clinical adverse events, of which 4 studies (6,31,34,36) had data eligible for meta-analysis and 2 studies (6, 31) reported laboratory adverse events. Details of outcome findings of each individual study are listed in Table 1. ...
Objectives
To assess and summarize current evidence on the effectiveness and safety of ertapenem for treatment of childhood infections, in consideration of high infection prevalence in children and wide use of ertapenem.
Methods
The following 8 databases were searched on 13th May 2021: Web of Science, Embase via Ovid SP, PubMed, The Cochrane Library (CENTRAL), Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP and Wanfang. The primary outcome was treatment success rate. Risk ratios (RRs) and 95% confidence interval (CI) were estimated using random-effect models. Subgroup analysis was conducted where heterogeneity was found.
Results
Fifteen studies (8 randomized controlled trials, 1 observational comparative study, and 6 before and after studies) involving 2,528 patients were included in the final review. Ertapenem had similar treatment success rates with β-lactam antibiotics [relative risk (RR) = 1.08, 95% CI: 0.99–1.19]. In a subgroup analysis, similar efficacy (RR = 1.08, 95% CI: 0.97–1.20) between ertapenem and other carbapenems. Compared with β-lactam antibiotics, ertapenem did not increase the risk of any adverse events (RR = 1.02, 95%CI: 0.71–1.48), drug-related diarrhea (all non-Asian children, RR = 0.62, 95%CI: 0.31–1.25), or injection site pain (all non-Asian children, RR = 1.66, 95%CI: 0.59–4.68). Subgroup analysis showed no obvious difference between ertapenem group and carbapenems or non-carbapenems group on risk of adverse events.
Conclusion
Our findings suggest that ertapenem is effective and safe in treatment for children with infection. Further comparative real-world data is needed to supplement clinical evidence on the overall benefits of ertapenem in this population.
... [5]. One the other hand, once-daily ertapenem, a carbapenem antibiotic, may be a useful alternative for the treatment of pediatric patients with mixed aerobic and anaerobic infections and severe intra-abdominal infections [6]. ...
... 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]. ...
... 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]. ...
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.
... Resistance is a natural biological outcome of antibiotic use. Antibiotic overtreatment, however, increases the speed of emergence and selection of resistant bacteria [47,48]. It is plausible that reducing the duration of antibiotic treatment may not increase the rate of IAA, as the development of infectious complications following appendectomy is a multifactorial process. ...
... Though unfortunately no exact duration of antibiotics was reported, mean LOS was significantly reduced from 6 to 4 days, while IAA rates were similar in both groups [28]. Moreover, several studies in which different antibiotic agents are compared, both given for not more than 3 days, report rather acceptable rates of infectious complications [48,[53][54][55][56]. ...
Postoperative antibiotics are recommended after appendectomy for complex appendicitis to reduce infectious complications. The duration of this treatment varies considerably between and even within institutions. The aim of this review was to critically appraise studies on duration of antibiotic treatment following appendectomy for complex appendicitis. A systematic literature search according to the PRISMA guidelines was performed. Comparative studies evaluating different durations of postoperative antibiotic therapy. Primary endpoint was intra-abdominal abscess (IAA) after appendectomy. Secondary endpoints were surgical site infection, readmission and length of hospital stay. The quality of evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Pooled event rates were calculated using a random-effects model. Nine studies reporting 2006 patients with complex appendicitis were included. The methodological quality of the included articles was poor. IAA was seen in 138 patients (8,6%). Meta-analysis revealed a statistically significant difference in IAA incidence between antibiotic treatment of ≤5 vs. >5 days (risk ratio (OR) 0.36 [95% CI 0.23–0.57] (p < 0.0001)) but not between ≤3 vs. >3 days (OR 0.81 [95% CI 0.38–1.74] (p = 0.59)). Descriptive statistics were used for secondary endpoints. The duration of postoperative antibiotic treatment is not associated with IAA following appendectomy for complex appendicitis.
... Dalgic et al. 16 Post-discharge organ-space infections occurred in 4/86 (4.7%) of those with antibiotics and 9/277 (3.2%) of those without (p = 0.54). Superficial and . ...
Objective
Surgical site infections (SSIs), especially deep/organ-space SSIs, are common and serious complications following appendectomy. This review aimed to explore the interventions that have been implemented to reduce the risk of SSIs in pediatric appendicitis patients.
Methods
A literature search was performed using PubMed, Cochrane, and Embase databases of studies in English published between January 01, 1973, and April 30, 2023. Studies on pediatric patients (≤ 18 years) with appendicitis that described any interventions aimed at reducing SSIs and reported SSIs as an outcome were included.
Results
A total of 56 studies were included in the final scoping review. The interventions included antibiotic stewardship, clinical practice guidelines/pathways, different surgical approaches, timing of appendectomy, irrigation or lavage, use of peritoneal drains, timing of wound closure and management, parenteral nutrition, pain management, and outpatient management.
Conclusion
A wide variety of interventions have been studied in pediatric appendicitis patients to reduce the SSI rates. Very few publications have studied low-cost, widely available intraoperative interventions to reduce deep/organ-space SSIs.
Background: Exploration of the risk factors of recurrent appendiceal abscess after initial non-surgical treatment without drainage in children with appendiceal abscess. Patients and Methods: The medical records of all children diagnosed with appendiceal abscess and who were treated conservatively in the Children's Hospital of Chongqing Medical University from June 2012 to June 2020 were collected. The collected cases were divided into the recurrent group and the non-recurrent group, and all clinical indicators were compared. Logistic regression analysis was used to determine the risk factors for recurrent appendiceal abscess in children. Results: One hundred twenty-four patients were included and among them, 62 (50.0%) had clinical manifestations of recurrent appendiceal abscess (the recurrent group) and five patients (8%) suffered several instances of recurrence. Duration of intravenous antibiotic agents (odds ratio [OR], 0.905; 95% confidence interval [CI], 0.820-1.000) was independently associated with the recurrence of appendiceal abscess. The risk of recurrence was increased in children with the white blood cell (WBC) count at discharge greater than 8 × 109/L (OR, 2.702; 95% CI,1.172-6.231), the ratio of mass size to body surface area (BSA) at discharge greater than 4.255 (OR, 1.369; 95% CI, 1.104-1.697), and without continuous oral antibiotic agents after discharge (OR, 3.111; 95% CI, 1.240-7. 802). Conclusions: Interval appendectomy is recommended for children with WBC count at discharge greater than 8 × 109/L, and the ratio of mass size to BSA at discharge greater than 4.255, because they are more likely to develop recurrent appendiceal abscess after initial conservative treatment. The duration of intravenous antibiotic agents is an independent factor of the recurrence of appendiceal abscess, and a longer course of intravenous antibiotic agents is strongly associated with a reduced risk of recurrence. Continued oral antibiotic agents after discharge can effectively reduce the risk of recurrence of appendiceal abscesses.
Eosinophilic cystitis (EC) is a rare inflammatory disease characterized by infiltration of eosinophils
in the layers of the bladder wall.
The objective of the following work is to present our series of pediatric patients with eosinophilic
cystitis and describe the different forms of presentation.
Clinical histories of patients in whom the pathological anatomy diagnosed CE were analyzed.
In the analyzed period, four patients with a diagnosis of eosinophilic cystitis were presented. Dysuria
was the most common symptom, followed by macroscopic hematuria. The medical treatment was performed
in two patients, the other two patients were treated only with endoscopic resection of the polyps.
At 6 months, all were free of symptoms and without evidence of ultrasound lesions.
Although eosinophilic cystitis has a benign course, patients should be controlled in the long term
for the possibility of recurrence.
Purpose:
Randomized controlled trials (RCT) in pediatric appendicitis remain limited, and the robustness of available evidence is unknown. The aim of this study was to determine the fragility of results in pediatric appendicitis RCTs.
Methods:
A systematic search of Embase and MEDLINE was performed. Eligible studies were two-armed RCTs that included at least one statistically significant dichotomous outcome, had parallel-group allocation, and assessed pediatric patients (0-17) with a primary diagnosis of appendicitis. The Fragility Index (FI) for one statistically significant outcome per trial was calculated using a Fisher's exact test, with statistical significance set at p < 0.05.
Results:
Six studies were identified for inclusion. Studies included a median of 103 patients (interquartile range [IQR] 86-127), with a median of 18 (IQR 4.5-41.25) events for analyzed outcomes. The primary outcome variable was included in analysis for 4(67%) studies. The median FI across studies was 3 (IQR 0.75-4.25), with results ranging from 0 to 5. Results indicate that overall, converting 3 patients from non-events to events in a single trial arm would change the significant dichotomous outcome to nonsignificant.
Conclusion:
The fragility of results in RCTs in pediatric appendicitis should be considered before clinical practice is changed. Investigators should consider reporting the FI alongside study results, as p-values alone may be misleading.
Type of study:
Randomized Controlled Trial.
Level of evidence:
Level I.
Objective:
To analyze the preoperative use of antibiotics in children and adolescents requiring appendectomy.
Data source:
Integrative review was performed in the MEDLINE, Latin American and Caribbean Health Sciences (LILACS) and Cochrane databases and the PubMed portal, with no time limit. The keywords used were: appendicitis, child, adolescent and antibacterial with Boolean AND. The articles included were published in Portuguese, English or Spanish and whose participants were under 18 years of age. Review articles and guidelines were excluded. The studies were classified according to their level of evidence and 24 papers were selected.
Data collection and analysis:
Seven randomized clinical trial studies (level of evidence II), eight cohorts (level III), seven retrospective observational studies (level V) and two historical documentary analysis (level IV) were selected. The studies addressed antibiotics used in acute appendicitis in both uncomplicated and complicated cases. Antibiotics initiated in the preoperative period showed a decrease in the rates of surgical wound infections. First-line (empiric) regimens were tested for sensitivity to microorganisms in peritoneal material cultures, however the results were controversial. Broad-spectrum antibiotics have been suggested in some studies because they have good coverage, but in others they have not been recommended because of the risk of developing bacterial resistance. Shorter administration time and earlier change to the oral route reduced hospitalization time.
Conclusions:
There are several clinical protocols with different antibiotics. However, there is no standardization concerning the type of antibiotic drug, time of use, or route.
A mouse model was used to test the hypothesis that antibiotics with activity against anaerobes promote overgrowth of extended-spectrum
β-lactamase-producing Klebsiella pneumoniae strains in stool. Subcutaneous clindamycin consistently promoted establishment of high-density colonization, whereas piperacillin-tazobactam,
ceftriaxone, and ceftazidime promoted colonization only when a large inoculum and/or more resistant strain was administered.
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.
Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL-producing organisms are
not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia colifor ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology
laboratories did not make efforts to detect ESBLs. We performed a prospective, multinational study of Klebsiella pneumoniae bacteremia and identified 10 patients who were treated for ESBL-producingK. pneumoniae bacteremia with cephalosporins and whose infecting organisms were not resistant in vitro to the utilized cephalosporin. In
addition, we reviewed 26 similar cases of severe infections which had previously been reported. Of these 36 patients, 4 had
to be excluded from analysis. Of the remaining 32 patients, 100% (4 of 4) patients experienced clinical failure when MICs
of the cephalosporin used for treatment were in the intermediate range and 54% (15 of 28) experienced failure when MICs of
the cephalosporin used for treatment were in the susceptible range. Thus, it is clinically important to detect ESBL production
by klebsiellae or E. coli even when cephalosporin MICs are in the susceptible range (≤ 8 μg/ml) and to report ESBL-producing organisms as resistant
to aztreonam and all cephalosporins (with the exception of cephamycins).
Study objective
To evaluate the relationship between inadequate antimicrobial treatment of infections (both community-acquired and nosocomial infections) and hospital mortality for patients requiring ICU admission.
Design
Prospective cohort study.
Setting
Barnes-Jewish Hospital, a university-affiliated urban teaching hospital.
Patients
Two thousand consecutive patients requiring admission to the medical or surgical ICU.
Interventions
Prospective patient surveillance and data collection.
Measurements and results
One hundred sixty-nine (8.5%) infected patients received inadequate antimicrobial treatment of their infections. This represented 25.8% of the 655 patients assessed to have either community-acquired or nosocomial infections. The occurrence of inadequate antimicrobial treatment of infection was most common among patients with nosocomial infections, which developed after treatment of a community-acquired infection (45.2%), followed by patients with nosocomial infections alone (34.3%) and patients with community-acquired infections alone (17.1%) (p < 0.001). Multiple logistic regression analysis, using only the cohort of infected patients (n = 655), demonstrated that the prior administration of antibiotics (adjusted odds ratio [OR], 3.39; 95% confidence interval [CI], 2.88 to 4.23; p < 0.001), presence of a bloodstream infection (adjusted OR, 1.88; 95% CI, 1.52 to 2.32; p = 0.003), increasing acute physiology and chronic health evaluation (APACHE) II scores (adjusted OR, 1.04; 95% CI, 1.03 to 1.05; p = 0.002), and decreasing patient age (adjusted OR, 1.01; 95% CI, 1.01 to 1.02; p = 0.012) were independently associated with the administration of inadequate antimicrobial treatment. The hospital mortality rate of infected patients receiving inadequate antimicrobial treatment (52.1%) was statistically greater than the hospital mortality rate of the remaining patients in the cohort (n = 1,831) without this risk factor (12.2%) (relative risk [RR], 4.26; 95% CI, 3.52 to 5.15; p < 0.001). Similarly, the infection-related mortality rate for infected patients receiving inadequate antimicrobial treatment (42.0%) was significantly greater than the infection-related mortality rate of infected patients receiving adequate antimicrobial treatment (17.7%) (RR, 2.37; 95% CI, 1.83 to 3.08; p < 0.001). Using a logistic regression model, inadequate antimicrobial treatment of infection was found to be the most important independent determinant of hospital mortality for the entire patient cohort (adjusted OR, 4.27; 95% CI, 3.35 to 5.44; p < 0.001). The other identified independent determinants of hospital mortality included the number of acquired organ system derangements, use of vasopressor agents, the presence of an underlying malignancy, increasing APACHE II scores, increasing age, and having a nonsurgical diagnosis at the time of ICU admission.
Conclusions
Inadequate treatment of infections among patients requiring ICU admission appears to be an important determinant of hospital mortality. These data suggest that clinical efforts aimed at reducing the occurrence of inadequate antimicrobial treatment could improve the outcomes of critically ill patients. Additionally, prior antimicrobial therapy should be recognized as an important risk factor for the administration of inadequate antimicrobial treatment among ICU patients with clinically suspected infections.
Background
We aimed to define the epidemiological associations of vancomycin-resistant enterococci (VRE) in intensive care units (ICUs) during a non–outbreak period by examining prevalence, risk factors for colonization, frequency of acquisition, and molecular strain types.
Design
A prospective cohort design was followed. Consecutive patient admissions to 2 surgical ICUs at a tertiary care hospital were enrolled. The main outcome measures were results of serial surveillance cultures screened for VRE.
Results
Of 290 patients enrolled, 35 (12%) had colonization with VRE on admission. The VRE colonization or infection had been previously detected by clinical cultures in only 4 of these patients. Using logistic regression, VRE colonization at the time of ICU admission was associated with second- and third-generation cephalosporins (odds ratio [OR]=6.0, P<.0001), length of stay prior to surgical ICU admission (OR=1.06, P=.01) greater than 1 prior ICU stay (OR=9.6, P=.002), and a history of solid-organ transplantation (OR=3.8, P=.021). Eleven (12.8%) of 78 patients with follow-up cultures acquired VRE. By pulsed-field gel electrophoresis, 2 strains predominated, one of which was associated with an overt outbreak on a non-ICU ward near the end of the study period.
Conclusions
Colonization was common and usually not recognized by clinical culture. Most patients who had colonization with VRE and were on the surgical ICU acquired VRE prior to surgical ICU entry. Exposure to second- and third-generation cephalosporins, but not vancomycin, was an independent risk factor for colonization. Prospective surveillance of hospitalized patients may yield useful insights about the dissemination of nosocomial VRE beyond what is appreciated by clinical cultures alone.
Background:
The role of laparoscopy in the setting of perforated appendicitis remains controversial. A retrospective study was conducted to evaluate the early postoperative outcomes of laparoscopic appendectomy (LA) compared to open appendectomy (OA) in patients with perforated appendicitis.
Methods:
A total of 1,032 patients required an appendectomy between January 2005 and December 2009. Among these patients, 169 presented with perforated appendicitis. Operation times, length of hospital stay, overall complication rates within 30 days, and surgical site infection (SSI) rates were analyzed.
Results:
Out of the 169 evaluated patients, 106 required LA and 63 OA. Although operation times were similar in both groups (92 ± 31 min for LA vs. 98 ± 45 for OA, p = 0.338), length of hospital stay was shorter in the LA group (6.9 ± 3.8 days vs. 11.5 ± 9.2, p < 0.001). Overall complication rates were significantly lower in the LA group (32.1 vs. 52.4 %, p < 0.001), as were incisional SSI (1.9 vs. 22.2 %, p < 0.001). Organ/space SSI rates were similar in both groups (23.6 % after LA vs. 20.6 % after OA, p = 0.657).
Conclusions:
For perforated appendicitis, LA results in a significantly shorter hospital stay, fewer overall postoperative complications, and fewer wound infections compared to OA. Organ/space SSI rates were similar for both procedures. LA provides a safe option for treating patients with perforated appendicitis.
The carbapenem antibiotic ertapenem has been shown to be safe, well tolerated and effective in treating adults with complicated urinary tract infection, skin and soft-tissue infection and community-acquired pneumonia. In this study, we evaluated ertapenem for treating these infections in children in a randomised, double-blind, active-controlled clinical trial. The primary outcome was the incidence of clinical and laboratory drug-related serious adverse events (AEs). Children were randomised in a 3:1 ratio (ertapenem:ceftriaxone) stratified by index infection and age to receive ertapenem or ceftriaxone; 303 children received ertapenem and 100 children received ceftriaxone. The median duration of parenteral therapy was 4 days for both treatments. The most commonly reported drug-related clinical AEs during parenteral therapy were diarrhoea (5.9% ertapenem, 10% ceftriaxone), infusion site erythema (3% ertapenem, 2% ceftriaxone) and infusion site pain (5% ertapenem, 1% ceftriaxone). One child in each group reported a serious drug-related clinical AE. No serious drug-related laboratory AEs were reported. In children aged 3 months to 17 years, ertapenem was well tolerated and had a comparable safety profile to that of ceftriaxone.
The influence of ceftriaxone on oral and intestinal flora was investigated in 10 patients undergoing colorectal surgery. Ceftriaxone was given intravenously in one 2g dose before anesthesia. Saliva and feces samples were collected and analyzed on day 0, 3, 5, 14 and 28 after drug administration. All specimens were cultured quantitatively for aerobic and anaerobic microorganisms; representative colonies of each morphologic type of organism cultured were identified. The oral aerobic flora was somewhat affected by the administration of ceftriaxone. In all patients the number of Streptococci, Staphylococci and Neisseria decreased during the 5 days after ceftriaxone administration. No significant changes in the number of anaerobic commensal occurred. The oral microflora of all patients after 14 days had returned to normal. The aerobic fecal flora was considerably affected: in all patients enterobacteria were eliminated or strongly suppressed. Only minor changes in the number of aerobic gram-positive bacteria were observed, and the anaerobic intestinal flora showed only minor alterations. On day 28 the intestinal flora were normalized in all respects. No new colonizing microorganisms were isolated during the investigation period and no colonization with ceftriaxone-resistant bacteria was observed. No postoperative infection occurred and no adverse effects were registered.
Six adult volunteers were given 1 g/d of intravenous ceftriaxone for 5 d (consecutive). Ceftriaxone and β-lactamaseactivities
were assayed in fecal samples obtained before and during drug administration, and anaerobic bacteria, Enterobacteriaceae,
and fungi were counted. In two volunteers, no fecal β-lactamase activity was detected, but ceftriaxone was present during
treatment at concentrations of 1.8–2.0 mg/g of feces. Concomitantly, fecal counts of anaerobes in these volunteers dropped
from 10.5to <8 log10 colony-forming units (cfu)/g of feces, and those of Candida species increased more than 100-fold. However, in the feces of the four other volunteers, β-lactamase activity was high during
ceftriaxone administration, but no ceftriaxone was detected. In these volunteers, ceftriaxone administration was not followed
by any significant change in counts of anaerobes or Candida species. This appeared to be due to the intraintestinal hydrolysis of ceftriaxone by resident β-lactamase-producing anaerobes.
In gnotobiotic mice associated with a human fecal flora containing no β-lactamase-producing anaerobes, it was possible to
prevent the deleterious effects of ceftriaxone on intestinal microbial composition and on colonization resistance (against
a strain of Candida albicans and one of ceftriaxone-resistant Enterobacter cloacae) by feeding the animals with an association of four β-lactamase-producing anaerobic strains.
Excretion of an antibiotic bile may result in high intraintestinal concentrations and thus alteration in the fecal flora. We investigated the effect of ceftriaxone (45% biliary excretion) and cefotaxime (less than 5% biliary excretion) on the aerobic fecal flora. Ceftriaxone eradicated susceptible enteric organisms and resulted in overgrowth of Candida spp. and resistant enterococci. In some patients multiresistant gram negative bacteria appeared during of after therapy. Cefotaxime had a moderate effect on fecal microecology and did not promote the emergence of resistant organisms.