Agreement between rapid antigen detection test and culture for group A streptococcus in patients recently treated for pharyngotonsillitis - a prospective observational study in primary care.

OBJECTIVE: The aim was to compare rapid antigen detection test (RADT) and throat culture for group A streptococci (GAS) among patients recently treated with penicillin V for GAS pharyngotonsillitis. DESIGN AND SETTING: The study was a secondary analysis within a randomized controlled trial comparing 5 versus 10 days of penicillin V for GAS pharyngotonsillitis. Patients were recruited at 17 primary health care centres in Sweden. SUBJECTS: We included 316 patients ≥ 6 years of age, having 3-4 Centor criteria, a positive RADT and a positive throat culture for GAS at inclusion, and also having a RADT and throat culture for GAS taken at a follow-up visit within 21 days. MAIN OUTCOME MEASURES: RADT and conventional throat culture for GAS. RESULTS: This prospective study showed 91% agreement between RADT and culture at follow-up within 21 days. Only 3/316 participants had negative RADT with a positive throat culture for GAS at follow-up, and 27/316 patients with positive RADT had a negative culture for GAS. Log rank test did not reveal any difference in the decline over time of positive tests between RADT and throat culture (p = 0.24). Agreement between RADT and throat culture for GAS at the follow-up was not associated with treatment duration, number of days from inclusion until follow-up, throat symptoms at follow-up, gender, or age. CONCLUSION: RADT and culture for GAS agreed to a high extent also after recent penicillin V treatment. RADT for GAS means a low risk for missing the presence of GAS.KEY POINTSTesting for group A streptococci (GAS) before antibiotic treatment can reduce antibiotic prescription for pharyngotonsillitis. It has been proposed that rapid antigen detection tests (RADT) for group A streptococci after recent penicillin V treatment may be falsely positive due to possible persisting antigens from non-viable bacteria.The decline of the presence of GAS was similar between RADT and conventional throat culture in patients who had recently completed penicillin V treatment for GAS pharyngotonsillitisRADT for GAS is useful in identifying the presence of GAS after recent penicillin V treatment.

Effects of penicillin V on the faecal microbiota in patients with pharyngotonsillitis-an observational study.

Background: The intestinal microbiota functions as a reservoir of antibiotic resistance. Objectives: To evaluate penicillin V (phenoxymethylpenicillin) effects on the faecal microbiota with focus on beta-lactam resistance. Methods: We included 31 primary care patients with group A streptococcal pharyngotonsillitis treated with penicillin V for 5 (800 mg × 4) or 10 days (1000 mg × 3). Twenty-nine patients contributed with three faecal swab samples each. The faecal specimens were collected at the start of penicillin V treatment, after the last dose and at follow-up 7-9 days after completed treatment. Samples were inoculated semiquantitatively on selective screening agar plates to study beta-lactam resistance, species shifts among Enterobacterales and enterococci, and colonization with Candida spp. and Clostridioides difficile. Representative colonies were identified using MALDI-TOF. Results were analysed by non-parametric statistical methods. Results: An increase in the proportion of patients colonized with ampicillin-resistant Enterobacterales, from 52% to 86% (P = 0.007), and Enterobacterales with decreased susceptibility to third-generation cephalosporins, from 32% to 52% (P = 0.034), was observed between the first and second samples. This increase was no longer significant at follow-up. New colonization with ampicillin-resistant Enterobacterales species and non-Enterobacterales Gram-negative species was observed, and persisted at follow-up. Conclusions: Following treatment with penicillin V, we observed decreased susceptibility to ampicillin and third-generation cephalosporins, and prolonged colonization with non-Escherichia coli Gram-negative species. These findings challenge the perception that penicillin V has limited ecological effect on the intestinal microbiota, and emphasizes the importance of avoiding even narrow-spectrum antimicrobials when possible.

Clinical course of pharyngotonsillitis with group A streptococcus treated with different penicillin V strategies, divided in groups of Centor Score 3 and 4: a prospective study in primary care.

BACKGROUND: Sore throat is a common reason for prescribing antibiotics in primary care, and 10 days of treatment is recommended for patients with pharyngotonsillitis with group A streptococcus (GAS). Our group recently showed that penicillin V (PcV) four times daily for 5 days was non-inferior in clinical outcome to PcV three times daily for 10 days. This study compares duration, intensity of symptoms, and side effects in patients with a Centor Score (CS) of 3 or 4 respectively, after treatment with PcV for 5 or 10 days and evaluates whether all patients with pharyngotonsillitis with a CS of 3 or 4 should be treated for 5 days or if severity of symptoms or CS suggest a longer treatment period. METHOD: Data on symptoms and recovery from patient diaries from 433 patients included in a RCT comparing PcV 800 mg × 4 for 5 days or PcV 1 g × 3 for 10 days was used. Patients six years and older with CS-3 or CS-4 and positive rapid antigen detection test for GAS-infection were grouped based on CS and randomized treatment. Comparisons for categorical variables were made with Pearson's chi-squared test or Fisher's exact test. Continuous variables were compared with the Mann-Whitney U test. RESULTS: Patients with CS-3 as well as patients with CS-4 who received PcV 800 mg × 4 for 5 days self-reported that they recovered earlier compared to patients with CS-3 or CS-4 who received treatment with PcV 1 g × 3 for 10 days. In addition, the throat pain as single symptom was relieved 1 day earlier in patients with CS-4 and 5 days of treatment compared to patients with CS-4 and 10 days of treatment. No differences in side effects between the groups were found. CONCLUSION: Intense treatment with PcV four times a day for 5 days seems clinically beneficial and strengthens the suggestion that the 4-dose regimen with 800 mg PcV for 5 days may be the future treatment strategy for GAS positive pharyngotonsillitis irrespectively of CS-3 or CS-4. Trail registration ClinicalTrials.gov ID: NCT02712307 (3 April 2016).

Cost-Effectiveness Analysis of Temocillin Treatment in Patients with Febrile UTI Accounting for the Emergence of Antibiotic Resistance.

BACKGROUND: Antibiotic resistance has been listed as one of the biggest threats to global health today. A recent study has shown that treating febrile urinary tract infections with temocillin instead of cefotaxime leads to a reduced selection of antibiotic-resistant bacteria. However, a potential challenge with prioritizing temocillin over cefotaxime is the cost consequences. OBJECTIVE: This study aimed to assess the cost effectiveness of using temocillin compared to cefotaxime in treating febrile urinary tract infections in a model that takes the emergence of antibiotic resistance into account. METHODS: We used a Markov cohort model to estimate the costs and health effects of temocillin and cefotaxime treatment in febrile urinary tract infections in a Swedish setting. Health effects were assessed in terms of quality-adjusted life-years, and the primary outcome was the cost per quality-adjusted life-year gained with temocillin compared to cefotaxime. We used a 5-year time horizon. RESULTS: The model results showed that temocillin treatment led to better health outcomes at a higher total cost. The cost per quality-adjusted life-year gained was approximately 38,400 EUR. Results from the sensitivity analysis suggested a 63% probability of temocillin being cost effective at a threshold of 50,000 EUR. Furthermore, results showed that the cost effectiveness of temocillin in febrile urinary tract infections is highly dependent on the drug cost. CONCLUSIONS: As antibiotic consumption is a driving force of resistance, it is essential to consider the development of resistance when studying the health economic consequences of antibiotic treatments. In doing so, this study found temocillin to be cost effective for febrile urinary tract infections.

The Swedish model for prioritising research on the use of antibiotics: Aligning public funding with research gaps.

Due to the meagre development of new antibiotics, optimising the use of currently available antibiotics is important to reduce resistance pressures and to safeguard existing treatment options. The Public Health Agency of Sweden (PHAS) was tasked in 2014 to (1) develop a model for identifying and prioritising research gaps and (2) initiate studies to improve knowledge on how to optimise the use of existing antibiotics. A survey addressing knowledge-gaps and suggesting studies needed was distributed to a broad network of Swedish and European clinicians and experts. An independent reference group prioritised the proposals, applying predefined criteria focusing on public health relevance. The PHAS sponsored and led two multi-centre RCTs in cooperation with clinical researchers and took part in additional studies. A second survey and prioritization exercise following the same model was performed in 2019. The Swedish case study described in this paper provides an example of the role that the public sector can play in order to support the improved use of existing antibiotics. National and international institutions are well suited to perform systematic reviews of research priorities with a focus on public health concerns. The ultimate success of the model depends on political engagement, a close dialogue with healthcare professionals, collaboration between international sister-authorities responsible for public health in other countries, the availability of research funding, harmonisation of regulatory issues and regular revisions of clinical guidelines. The experience from the Swedish model illustrates opportunities for meeting clinical needs and filling knowledge gaps on existing off-patent antibiotics.

The clinical and microbiological efficacy of temocillin versus cefotaxime in adults with febrile urinary tract infection, and its effects on the intestinal microbiota: a randomised multicentre clinical trial in Sweden.

BACKGROUND: Use of third-generation cephalosporins, such as cefotaxime, is associated with an increased risk of selection for antimicrobial resistance, so alternative antibiotics need to be considered. The aim of the present study was to evaluate intestinal colonisation with third-generation cephalosporin-resistant pathogens following use of temocillin-an alternative antibiotic to cefotaxime that is potentially less prone to disturbing the intestinal microbiota-in empirical treatment of febrile urinary tract infection (UTI). METHODS: We did a randomised, multicentre, superiority, open-label phase 4 trial in patients who had been admitted to inpatient care in 12 Swedish hospitals with suspected or diagnosed febrile UTI (complicated or uncomplicated). To meet inclusion criteria, a patient was required to have at least one sign or symptom of pyelonephritis (ie, flank pain; costovertebral angle tenderness; and changes to urinary frequency or urgency or dysuria), a fever of 38·0°C or higher, and a positive urine dipstick (for nitrites, white blood cells, or both). Participants were also required to have an indication for intravenous antibiotic treatment. Participants were randomly assigned (1:1) to receive either 2 g temocillin or 1-2 g cefotaxime, by local investigators opening consecutive sealed randomisation envelopes that were generated centrally in advance. Both drugs were administered intravenously every 8 h. The trial was open label for investigators and patients, but those doing the microbiological analyses were masked to the groups. Participants were treated with antibiotics for 7-10 days (or up to 14 days if they had bacteraemia), at least 3 days of which were on the study drug; at day 4 and later, participants who were showing improvement could be given an oral antibiotic (ciprofloxacin, ceftibuten, cefixime, or co-trimoxazole). Patients not showing improvement were regarded as having treatment failures. Rectal swabs were collected at three timepoints: at baseline (before the first dose), after the last dose of study drug, and 7-10 days after treatment stopped. The composite primary outcome was colonisation with Enterobacterales with reduced susceptibility to third-generation cephalosporins, or colonisation with toxin-producing Clostridioides difficile, or both, to evaluate disturbance of the intestinal microbiota. The study is registered in the EU Clinical Trials Register (EudraCT 2015-003898-15). FINDINGS: Between May 20, 2016, and July 31, 2019, 207 patients were screened for eligibility, of whom 55 patients were excluded. 152 participants were randomly assigned to groups: 77 (51%) patients received temocillin, 75 (49%) patients received cefotaxime. The composite primary endpoint was met by 18 (26%) of 68 participants receiving temocillin versus 30 (48%) of 62 patients receiving cefotaxime (risk difference -22% [95% CI -42% to -3%]), showing superiority of temocillin versus cefotaxime (ie, less disturbance of the intestinal microbiota). 43 adverse events were reported in 40 (52%) of 77 patients in the temocillin group, versus 46 adverse events in 34 (45%) of 75 patients in the cefotaxime group. Most events were of mild to moderate severity. 21 (27%) patients in the temocillin and 17 (23%) patients in the cefotaxime group had an adverse event that was considered to be associated with the study drug. INTERPRETATION: Temocillin was found to be less selective than cefotaxime of Enterobacterales with reduced susceptibility to third-generation cephalosporins, and it could therefore be a favourable alternative in the empirical treatment of febrile UTI. Use of this antibiotic could reduce hospital transmission and health-care-associated infections by these pathogens. FUNDING: Public Health Agency of Sweden.

Penicillin V four times daily for five days versus three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci: randomised controlled, open label, non-inferiority study.

OBJECTIVE: To determine whether total exposure to penicillin V can be reduced while maintaining adequate clinical efficacy when treating pharyngotonsillitis caused by group A streptococci. DESIGN: Open label, randomised controlled non-inferiority study. SETTING: 17 primary healthcare centres in Sweden between September 2015 and February 2018. PARTICIPANTS: Patients aged 6 years and over with pharyngotonsillitis caused by group A streptococci and three or four Centor criteria (fever ≥38.5°C, tender lymph nodes, coatings of the tonsils, and absence of cough). INTERVENTIONS: Penicillin V 800 mg four times daily for five days (total 16 g) compared with the current recommended dose of 1000 mg three times daily for 10 days (total 30 g). MAIN OUTCOME MEASURES: Primary outcome was clinical cure five to seven days after the end of antibiotic treatment. The non-inferiority margin was prespecified to 10 percentage points. Secondary outcomes were bacteriological eradication, time to relief of symptoms, frequency of relapses, complications and new tonsillitis, and patterns of adverse events. RESULTS: Patients (n=433) were randomly allocated to the five day (n=215) or 10 day (n=218) regimen. Clinical cure in the per protocol population was 89.6% (n=181/202) in the five day group and 93.3% (n=182/195) in the 10 day group (95% confidence interval -9.7 to 2.2). Bacteriological eradication was 80.4% (n=156/194) in the five day group and 90.7% (n=165/182) in the 10 day group. Eight and seven patients had relapses, no patients and four patients had complications, and six and 13 patients had new tonsillitis in the five day and 10 day groups, respectively. Time to relief of symptoms was shorter in the five day group. Adverse events were mainly diarrhoea, nausea, and vulvovaginal disorders; the 10 day group had higher incidence and longer duration of adverse events. CONCLUSIONS: Penicillin V four times daily for five days was non-inferior in clinical outcome to penicillin V three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci. The number of relapses and complications did not differ between the two intervention groups. Five day treatment with penicillin V four times daily might be an alternative to the currently recommended 10 day regimen. TRIAL REGISTRATION: EudraCT 2015-001752-30; ClinicalTrials.gov NCT02712307.

A randomized controlled study of 5 and 10 days treatment with phenoxymethylpenicillin for pharyngotonsillitis caused by streptococcus group A - a protocol study.

BACKGROUND: In 2014 the Swedish government assigned to The Public Health Agency of Sweden to conduct studies to evaluate optimal use of existing antibiotic agents. The aim is to optimize drug use and dosing regimens to improve the clinical efficacy. The present study was selected following a structured prioritizing process by independent experts. METHODS: This phase IV study is a randomized, open-label, multicenter study with non-inferiority design regarding the therapeutic use of penicillin V with two parallel groups. The overall aim is to study if the total exposure with penicillin V can be reduced from 1000 mg three times daily for 10 days to 800 mg four times daily for 5 days when treating Streptococcus pyogenes (Lancefield group A) pharyngotonsillitis. Patients will be recruited from 17 primary health care centers in Sweden. Adult men and women, youth and children ≥6 years of age who consult for sore throat and is judged to have a pharyngotonsillitis, with 3-4 Centor criteria and a positive rapid test for group A streptococci, will be included in the study. The primary outcome is clinical cure 5-7 days after discontinuation of antibiotic treatment. Follow-up controls will be done by telephone after 1 and 3 months. Throat symptoms, potential relapses and complications will be monitored, as well as adverse events. Patients (n = 432) will be included during 2 years. DISCUSSION: In the era of increasing antimicrobial resistance and the shortage of new antimicrobial agents it is necessary to revisit optimal usage of old antibiotics. Old antimicrobial drugs are often associated with inadequate knowledge on pharmacokinetics and pharmacodynamics and lack of optimized dosing regimens based on randomized controlled clinical trials. If a shorter and more potent treatment regimen is shown to be equivalent with the normal 10 day regimen this can imply great advantages for both patients (adherence, adverse events, resistance) and the community (resistance, drug costs). TRIAL REGISTRATION: EudraCT number 2015-001752-30 . Protocol FoHM/Tonsillit2015 date 22 June 2015, version 2. Approved by MPA of Sweden 3 July 2015, Approved by Regional Ethical Review Board in Lund, 25 June 2015.

Rational use of aminoglycosides--review and recommendations by the Swedish Reference Group for Antibiotics (SRGA).

The Swedish Reference Group for Antibiotics (SRGA) has carried out a risk-benefit analysis of aminoglycoside treatment based on clinical efficacy, antibacterial spectrum, and synergistic effect with beta-lactam antibiotics, endotoxin release, toxicity, and side effects. In addition, SRGA has considered optimal dosage schedules and advice on serum concentration monitoring, with respect to variability in volume of drug distribution and renal clearance. SRGA recommends that aminoglycoside therapy should be considered in the following situations: (1) progressive severe sepsis and septic shock, in combination with broad-spectrum beta-lactam antibiotics, (2) sepsis without shock, in combination with broad-spectrum beta-lactam antibiotics if the infection is suspected to be caused by multi-resistant Gram-negative pathogens, (3) pyelonephritis, in combination with a beta-lactam or quinolone until culture and susceptibility results are obtained, or as monotherapy if a serious allergy to beta-lactam or quinolone antibiotics exists, (4) serious infections caused by multi-resistant Gram-negative bacteria when other alternatives are lacking, and (5) endocarditis caused by difficult-to-treat pathogens when monotherapy with beta-lactam antibiotics is not sufficient. Amikacin is generally more active against extended-spectrum beta-lactamase (ESBL)-producing and quinolone-resistant Escherichia coli than other aminoglycosides, making it a better option in cases of suspected infection caused by multidrug-resistant Enterobacteriaceae. Based on their resistance data, local drug committees should decide on the choice of first-line aminoglycoside. Unfortunately, aminoglycoside use is rarely followed up with audiometry, and in Sweden we currently have no systematic surveillance of adverse events after aminoglycoside treatment. We recommend routine assessment of adverse effects, including hearing loss and impairment of renal function, if possible at the start and after treatment with aminoglycosides, and that these data should be included in hospital patient safety surveillance and national quality registries.

The global need for effective antibiotics-a summary of plenary presentations.

To highlight the global need for effective antibiotics and explore possible concerted actions for change, cross-cutting plenary sessions served to frame the program of the conference. These sessions contained presentations on the present state of antibacterial resistance and the availability, the use and misuse of antibiotics. A number of possible actions were discussed, such as rational use of and access to antibiotics from various perspectives. The roles of vaccines and diagnostics were touched upon and followed by in depth discussions on supply-side bottlenecks with their scientific, regulatory and financial challenges. The value chain for research and development (R&D) of antibiotics has to be reengineered if we are to realize the development of much needed new antibiotics. This challenge will require a multitude of actions, some of which are related to changing the financial realities of antibiotics and interventions by global and regional institutions.

Long-term impacts of antibiotic exposure on the human intestinal microbiota.

Although it is known that antibiotics have short-term impacts on the human microbiome, recent evidence demonstrates that the impacts of some antibiotics remain for extended periods of time. In addition, antibiotic-resistant strains can persist in the human host environment in the absence of selective pressure. Both molecular- and cultivation-based approaches have revealed ecological disturbances in the microbiota after antibiotic administration, in particular for specific members of the bacterial community that are susceptible or alternatively resistant to the antibiotic in question. A disturbing consequence of antibiotic treatment has been the long-term persistence of antibiotic resistance genes, for example in the human gut. These data warrant use of prudence in the administration of antibiotics that could aggravate the growing battle with emerging antibiotic-resistant pathogenic strains.

Metronidazole is still the drug of choice for treatment of anaerobic infections.

Metronidazole has been used for the treatment of infections for >45 years and is still successfully used for the treatment of trichomoniasis, amoebiasis, and giardiasis. Anaerobic bacterial infections caused by Bacteroides species, fusobacteria, and clostridia respond favorably to metronidazole therapy. Good clinical results in the treatment of vaginosis due to Gardnerella vaginalis have also been reported. Rates of resistance to metronidazole are still generally low; however, several studies have reported decreased susceptibility among Bacteroides species, as well as different mechanisms of resistance. Metronidazole-resistant Helicobacter pylori strains have been described, but combination therapy (eg, metronidazole, amoxicillin, or clarithromycin plus omeprazole) is still recommended for eradication of this pathogen in patients with gastroduodenal ulcers. Metronidazole is considered to be a cost-effective drug because of its low cost, good activity against pathogenic anaerobic bacteria, favorable pharmacokinetic and pharmacodynamic properties, and minor adverse effects. Metronidazole is still the criterion standard for therapy of anaerobic infections, as was described by Tally and colleagues 35 years ago.

Prolonged impact of a one-week course of clindamycin on Enterococcus spp. in human normal microbiota.

Human intestinal Enterococcus spp. was monitored during a 2-y period after 7 d clindamycin treatment. Consecutive faecal samples were collected from 8 healthy volunteers, 4 of whom had received clindamycin. After treatment, the number of enterococcal colonies was diminished and species variation extended. Erythromycin and clindamycin resistance increased from 19% to 69% and 0% to 67%, respectively. Elevated resistance levels lasted up to 9 months and erm(B) was detected in samples up to 6 months. Our results show that the clindamycin treatment had a prolonged impact on resistance and species variation.

Restored fitness leads to long-term persistence of resistant Bacteroides strains in the human intestine.

Acquired antibiotic resistance typically confers a cost to the bacteria, but these costs can be reduced by genetic compensation over time. The fitness of two Bacteroides thetaiotaomicron clones consecutively isolated in vivo was studied using an in vitro pair-wise competition method. The isolates derived from faecal samples of two clindamycin-exposed healthy volunteers and the two B. thetaiotaomicron clone types could be followed up to 18 months in these two subjects. The two clones were originally susceptible to clindamycin and lacked erm genes; however, after 7 days of clindamycin administration they carried the erm (erythromycin methylase)(G) or (F) gene, respectively, and expressed phenotypic clindamycin resistance. The initial cost of acquired resistance was high as seen in the in vitro pair-wise competition experiments. At 2 weeks post-administration, no growth disadvantage was detected for isolates of either of the two clones in the in vitro experiments and this regained fitness remained for isolates collected up to 18 months. Competition analysis of an in vitro isolated erm(G) positive transconjugant also demonstrated an initial reduction of fitness that was restored over time. The results indicate that the biological cost associated with a resistance gene can rapidly be compensated during in vivo growth. Thus, once the resistant clone has gained its resistance determinant it will be difficult to eliminate.

Invasive candidiasis in long-term patients at a multidisciplinary intensive care unit: Candida colonization index, risk factors, treatment and outcome.

The incidence of fungal infections in hospitalized patients has increased, and due to demographic changes and increasingly advanced medical methods, the intensive care units (ICU) have emerged as epicentres for fungal infections. The aim of the present study was to investigate Candida colonization pattern and colonization index (CI), in combination with other risk factors and its relation to invasive candida infection (ICI), in 59 consecutive patients with at least 7 d length of stay (LOS) at a multidisciplinary ICU. Surveillance samples were collected on d 7 and then weekly during the ICU stay. In addition, immunological status was monitored by measuring the histocompatibility leukocyte antigen-DR (HLA-DR). In the present study with a patient population burdened by several risk factors for ICI, 17% acquired an invasive infection. Overall ICU mortality was 30%. We could demonstrate that both a high colonization index and recent extensive gastroabdominal surgery were significantly correlated with ICI, while a decreased level of HLA-DR (< or = 70%) was not predictive for ICI in this high-risk population. The results indicate that ICU patients exposed to extensive gastroabdominal surgery would benefit from early antifungal prophylaxis.

Long-term ecological impacts of antibiotic administration on the human intestinal microbiota.

Antibiotic administration is known to cause short-term disturbances in the microbiota of the human gastrointestinal tract, but the potential long-term consequences have not been well studied. The aims of this study were to analyse the long-term impact of a 7-day clindamycin treatment on the faecal microbiota and to simultaneously monitor the ecological stability of the microbiota in a control group as a baseline for reference. Faecal samples from four clindamycin-exposed and four control subjects were collected at nine different time points over 2 years. Using a polyphasic approach, we observed highly significant disturbances in the bacterial community that persisted throughout the sampling period. In particular, a sharp decline in the clonal diversity of Bacteroides isolates, as assessed by repetitive sequence-based PCR (rep-PCR) and long-term persistence of highly resistant clones were found as a direct response to the antibiotic exposure. The Bacteroides community never returned to its original composition during the study period as assessed using the molecular fingerprinting technique, terminal restriction fragment length polymorphism (T-RFLP). Furthermore, using real-time PCR we found a dramatic and persistent increase in levels of specific resistance genes in DNA extracted from the faeces after clindamycin administration. The temporal variations in the microbiota of the control group were minor compared to the large and persistent shift seen in the exposed group. These results demonstrate that long after the selection pressure from a short antibiotic exposure has been removed, there are still persistent long term impacts on the human intestinal microbiota that remain for up to 2 years post-treatment.

Long-term antimicrobial resistance in Escherichia coli from human intestinal microbiota after administration of clindamycin.

The aim of this study was to gain better knowledge of how the intestinal microbiota are affected over time after administration of an antimicrobial agent. This study monitored the prevalence and frequencies of antibiotic resistance in Enterobacteriaceae against 17 antimicrobial agents, during a 2-y period, in consecutive faecal samples collected from 8 healthy volunteers. Four subjects had received 150 mg clindamycin perorally for 7 d, while 4 non-exposed subjects served as a control group. The samples from both groups were cultured and screened for Enterobacteriaceae. The highest incidence of resistance observed was to ampicillin. The ampicillin resistance is due to production of the beta-lactamase TEM-1. The administration of clindamycin had a prolonged impact on the composition of the microbiota, even though enterobacteria are intrinsically resistant to clindamycin; the level of resistance in Escherichia coli isolates was elevated after administration and persisted up to 9 months after administration. After 9 months the susceptibility levels in the exposed group were similar to those at d 0.