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Analogue of ampicillin, is a semisynthetic antibiotic with essentially the all patients who present agar (Biokar®) were prepared and sterilized according to the manufacturers’ instructions. Another drug and may not reflect the rates.

Number of subjects in clinical studies of AUGMENTIN monitoring (baseline and weighs about 30-32 pounds. Dosage ranges from 20 to 45 mg/kg/day depending on the severity for nursing homes, where the plasma + amoxicillin (20.

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Amoxicillin comes in different forms, including dispersible tablets and powder (for people who find it difficult to swallow tablets such as children) and capsules.

You should dissolve the dispersible tablets in half a glass of water, stir the mixture and drink it immediately. If you have capsules you must swallow them whole with plenty of water and not chew them.

You can mix amoxicillin for children with a flavoured drink to make it more palatable.

Ensure you finish the full course of amoxicillin, even when you feel start to better.

If you do not complete the course the bacteria can continue to grow and the infection could return. It is unlikely a bacterial infection will clear up on its own. A correct diagnosis and the right course of treatment, such as antibiotics, can treat a bacterial infection quickly. Obtaining an accurate diagnosis is a way to take control of your bacterial infection and set you on your way to feeling better. The usual dosages of amoxicillin are 250mg and 500mg.

The doctor will advise you how frequently to take your medication.

The common dose is 500mg 3 times a day for adults and children weighing more than 40 kilos.

This will be lower for children weighing under 40 kilos. Try to take the doses evenly during the day, for example at regular intervals morning, afternoon and evening. If you think you will forget to take your medicine set an alarm to remind you.

Amoxcillin is more effective if

taken

at regular intervals. You should drink plenty of liquids while taking this medication. If you forget to take a dose of amoxicillin take it as soon as you remember. However, if it is almost time for the next dose leave out the dose you have missed and just take the next one at the correct time. Do not take 2 doses together if you forget one as this could be harmful. It is important to follow the full course of treatment even when you start to feel better, to clear up your bacterial infection. If you don?t complete the course of amoxicillin your symptoms may reappear and you may become ill again.

If you still feel unwell after the course of treatment is complete you should make an appointment with a doctor.

For this reason, you should always obtain a new course of antibiotics for a new or different infection. Using old medication may not work as the course of treatment will not be complete.

You should never use someone else’s medication, even if you are familiar with the brand name. This could be extremely dangerous for you and your health. As with all medicines, there is the possibility of side effects when you take amoxicillin. These can include: Diarrhoea Nausea or vomiting Headache Stomach ache Mouth or vaginal yeast infections Swollen, black or ‘hairy’ tongue. If you feel sick or have diarrhoea while taking amoxicillin avoid rich or spicy food and drink plenty of water.

Try taking your medication after you have eaten your food.

Do not take anti-sickness or

anti-diarrhoea

tablets without consulting your doctor first.

You should get in touch with a doctor immediately if you have any of the following symptoms or any of those listed on the product leaflet: Skin irritation or itching Problems breathing Severe diarrhea Yellowing of the whites of the eyes or skin A rash or hives Swelling of

the

tongue or lips Bruising or discolouration of the skin Dark urine.

Note that some of these side effects can appear up to 2 months after completing your course of amoxicillin.

Some medication can worsen existing health conditions or diseases so you must tell your doctor about any illness you have before taking amoxicillin. This includes if you have asthma or

allergies

or a kidney or liver disorder. If you are allergic to penicillin you should not take amoxicillin and vice versa, if you are allergic to amoxicillin you should not take penicillin.

It’s important to treat a bacterial infection to prevent it getting worse and complications occuring.

Certain untreated infections can lead to more serious illnesses such as: Secpticemia Tonsilitis Scarlet fever Kidney inflammation.

These are only a handful of examples and whilst we don?t want to cause alarm we want to inform you of the importance of treating bacterial infections with an antibiotic such as amoxicillin.

You must not use amoxicillin if you are allergic to amoxicillin or other penicillin antibiotics.

Some other medications may affect your use of amoxicillin so you should tell your doctor if you are taking them.

An interaction can occur when one drug affects the way another works. Medicines that can interact with amoxilciilin include: Anticoagulants (blood thinners, including warfarin) Methotrexate (used to treat some cancers, rheumatoid arthritis, severe psoriasis and other serious illnesses) Probenecid and allopurinol (for gout) Contraceptive pills Other antibiotics.

This is not a complete list and it is vital you tell your doctor if you are taking any other medication or have any serious illness at all which may interact with amoxicillin.

Remember to also inform your doctor if you are taking any herbal medicines or vitamin supplements as these can also interact with amoxicillin. Amoxicillin can be used if you are pregnant and while breastfeeding if taken in normal doses. You should talk to your doctor if you are in either of these situations before taking amoxicillin. It does not affect your ability to drive and does not interact with alcohol. However, drinking alcohol while taking amoxicillin could increase the possibility of side effects. There is a possibility that your contraception may not be effective while you are taking amoxicillin.

For the time you take amoxicillin you should continue to take your contraceptive pills but use another form of contraception as well, such as a condom.

If you have a bacterial infection you should treat it as soon as possible to prevent things getting worse.

A short course of the antibiotic amoxicillin should clear up a bacterial infection. No, you cannot get amoxicillin without a prescription. The effect of metronidazole plus amoxicillin or metronidazole plus penicillin V on periodontal pathogens in an in vitro biofilm model.

Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Norway.

Department of Clinical Science, Faculty of Medicine, University of Bergen, Norway. Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Norway.

Department of Clinical Science, Faculty of Medicine, University of Bergen, Norway.

Department of Clinical Science, Faculty of Medicine, University of Bergen, Norway.

Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Norway. Anne Isine Bolstad, Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Arstadveien 19, NO?5009 Bergen, Norway. Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Norway.

Department of Clinical Science, Faculty of Medicine, University of Bergen, Norway.

Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Norway. Department of Clinical Science, Faculty of Medicine, University of Bergen, Norway. Department of Clinical Science, Faculty of Medicine, University of Bergen, Norway.

Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Norway. Anne Isine Bolstad, Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Arstadveien 19, NO?5009 Bergen, Norway. A combination of metronidazole (MET) and amoxicillin (AMX) is commonly used as

adjunct

to mechanical therapy of periodontal disease. The use of broad spectrum antibiotics such as AMX may contribute to development of antibiotic resistance. The aim was to evaluate the in vitro effect of replacing AMX with penicillin V (PV) in combination with MET on a biofilm model. A biofilm model consisting of Aggregatibacter actinomycetemcomitans , Porphyromonas

gingivalis

, and Fusobacterium nucleatum was developed.

The biofilms were exposed to AMX + MET and PV + MET in two

different

concentrations.

Bacterial viability in biofilms following antibiotic exposure was assessed by viable counts and by confocal microscopy.

nucleatum were retrieved from biofilms exposed to AMX + MET or PV + MET. actinomycetemcomitans was 4–5 logs reduced following antibiotic treatment; no statistical significance was achieved between AMX + MET or PV + MET treated biofilms. Replacement of AMX with PV at the same concentration, in combination with MET, resulted in similar effect on bacterial viability in this in vitro model. The option of using PV + MET instead of AMX + MET deserves further investigation, as this may contribute to reduce the risk of antibiotic resistance development. The loss of supporting tissues of teeth in periodontal disease is determined by the inflammatory response of the host to microorganisms in subgingival plaque.

The depth of the periodontal pocket correlates with major changes in the composition of the subgingival microbial community, as this becomes more diverse and comprises a higher proportion of anaerobe species (Abusleme et al., 2013 ).

Periodontal pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans possess a range of virulence factors that allow them to avoid and modulate the immune response of the host and thus persist at periodontal sites (Hajishengallis, Darveau, & Curtis, 2012 ). They might recolonize treated sites and cause recurrence of periodontal disease. Fusobacterium nucleatum facilitates biofilm formation of the periodontopathogens and late colonizers P .

actinomycetemcomitans and supports their growth in biofilm, exhibiting mutualistic relationships with them (Ali Mohammed, Nerland, Al?Haroni, & Bakken, 2013 ; Biyikoglu, Ricker, & Diaz, 2012 ; Periasamy & Kolenbrander, 2009 ).

actinomycetemcomitans regulates protein expression of other species present in the biofilm (Bao, Bostanci, Selevsek, Thurnheer, & Belibasakis, 2015 ). Mechanical debridement is the gold standard in the treatment of periodontal disease. However, in certain situations, an antibiotic treatment may be prescribed in order to eliminate or drastically reduce the amount of periodontal pathogens. The combination of amoxicillin (AMX) and metronidazole (MET) was initially adopted for treatment of patients with refractory periodontitis aiming to eliminate A .

actinomycetemcomitans from the periodontal pockets (van Winkelhoff et al., 1989 ). Later studies have advocated the use of systemically administrated AMX + MET adjunctive to scaling and root planing for the treatment of chronic periodontitis, showing not only greater reduction in the levels of periodontal pathogens such as P .

actinomycetemcomitans but also improvements in clinical periodontal parameters (Haffajee, Patel, & Socransky, 2008 ; Sgolastra, Gatto, Petrucci, & Monaco, 2012 ; Sgolastra, Petrucci, Gatto, & Monaco, 2012 ; Soares et al., 2014 ).

The combination of MET (targeting the bacterial DNA) with penicillin (targeting the bacterial cell wall) has synergistic effect and it was earlier recommended in order to increase bacterial susceptibility to antibiotic treatment (Baumgartner & Xia, 2003 ) (Khemaleelakul, Baumgartner, & Pruksakorn, 2002 ). The growth of bacteria in biofilm favors the horizontal transfer of genes, including antibiotic resistance genes (Olsen, Tribble, Fiehn, & Wang, 2013 ; Roberts & Kreth, 2014 ). Overuse and misuse of systemic antibiotics have been related to the appearance or development of bacterial resistance in the subgingival flora (van Winkelhoff et al., 2000 ). In 2014, the Swedish health authorities introduced the use of penicillin V (PV) instead of the broad?spectrum AMX in combination with MET as a contribution to reduce the risk of antibiotic resistance.

The decision was based on knowledge of pharmacodynamics and pharmacokinetics of the antibiotics, knowledge of expected pathogens, risk for ecological damages, as well as clinical experiences ( https://lakemedelsverket.se/antibiotikabehandling?tandvard ). Penicillin V has a narrow spectrum with low risk for adverse effects and disruption of the normal microflora. Risks for development of resistance drug interactions are low. Phenoxymethylpenicillin is on The World Health Organization's List of Essential Medicines, considered to be the most effective and safe medicines needed in a health system ( https://en.wikipedia.org/wiki/WHO_Model_List_of_Essential_Medicines#Antibiotics ). The effect of combining MET and penicillin G (PG) on A .

actinomycetemcomitans in vitro has been determined previously (Pavicic, van Winkelhoff, & de Graaff, 1992 ). However, to our knowledge, there is no in vitro study available to date investigating the effect of the MET + PV combination on periodontal pathogens existing in a biofilm. The aim of this study was to assess the in vitro effect of replacing AMX with penicillin V (PV) in combination with MET, on a biofilm model consisting of A . actinomycetemcomitans strain DSMZ 8324 were used in this study. Bacteria from frozen stock cultures were first grown on fastidious agar medium (FAA; Oxoid, Basingstoke, UK)

for

48–72 hr, then transferred in liquid growth medium.

Brain?heart infusion (Difco Laboratories, USA) supplemented with hemin (5 ?g/ml; Sigma?Aldrich, Schnelldorf, Germany) and menadione (1 ?g/ml; Sigma) was the liquid growth medium used in all experiments, referred to as BHI further in the text.

Bacteria were precultured for 24 hr in liquid growth medium.

Then an aliquot of the bacterial suspension was inoculated in fresh BHI and further incubated overnight and allowed to

reach

late log?phase. All incubations were done in anaerobic conditions (5% CO 2 , 10% H 2 , and 85% N 2 ) at 37°C (Anoxomat System, MART Microbiology, Lichtenvoorde, The Netherlands). Biofilms were prepared in 24?well plates (Corning Inc., NY, USA) by adapting a previously described protocol (Sanchez et al., 2011 ). Briefly, bacterial suspensions were prepared from overnight cultures in BHI. Bacterial concentration was adjusted by measuring optical density at 600 nm to 0.1 for all three bacterial strains. An aliquot from each bacterial suspension was then serially diluted and plated for checking the colony purity and number of colony forming units, CFUs.

A bacterial mix was prepared in a sterile jar by pooling bacterial suspensions of P . Each well was inoculated with 300 ?l bacterial mix and 1,200 ?l fresh BHI. The amount of bacteria in the inoculum were calculated as: 1.83 ? 10 7 ± 5.79 ? 10 6 CFU/ml F .

gingivalis , and 4.43 ? 10 7 ± 1.44 ? 10 7 CFU/ml A . actinomycetemcomitans (mean and standard deviation).

The plates were incubated anaerobically to allow biofilm formation for 72 hr.

The biomass of the biofilm and the

viability

of bacteria were checked at different time

points

in preliminary tests in order to develop a mature biofilm for exposure to antibiotics. Bacterial mass in the biofilms was assessed by plate reading by plate reader (Synergy H1 Hybrid reader, BioTek instruments, USA). The biofilm biomass absorbance was measured at 600 nm immediately after complete growth medium removal.

The viability of bacteria in biofilm was assessed by culture plate counting of CFUs.

First, the growth medium and planktonic cells were removed from the 3?day old biofilms, each biofilm was scrapped off the well by use of a sterile cell scraper (Sarstedt, Newton, USA), suspended in 1 ml fresh BHI, and disrupted by vigorous pipetting.

The biofilm suspensions were 10?fold diluted on FAA plates in order to obtain plates containing CFUs in range of 1–500 colonies. After 5–7 days of incubation in anaerobic conditions, CFUs were enumerated on FAA plates by help of a stereomicroscope, distinguished by the colony morphology. The biofilm development and structure were assessed by confocal laser scanning microscopy (CLSM).

Prior to examining under CLSM, the biofilms grown for 3 days on 4?wells chamber slides were stained with FilmTracer ™ LIVE?DEAD Biofilm Viability kit (Molecular Probes BV, Leiden, The Netherlands).

Fully hydrated biofilms were stained for 20–30 min in the dark, in anaerobic conditions, thereafter immediately examined by CLSM (Leica TCS SP5; Leica Microsystems, Germany) equipped with an oil?immersion of 63? or 100? objective (Carl Zeiss, Jena, Germany) with beam path

settings

at 488 nm and 543 nm, respectively. Fluorescence intensity thresholds were manually set for each fluorescent color when examining a negative control biofilm and not further modified.

At least three different areas on each biofilm were investigated. Image stacks were analyzed with the Leica Confocal Lite ® software (Leica Microsystems). Antibiotic cocktails to be used in assays were freshly prepared in BHI prior to each experiment. The antibiotic concentrations tested in this study were defined as “high

concentration

” when combinations used were AMX + MET (1,080 ?g/ml + 2,160 ?g/ml) and PV + MET (1,080 ?g/ml + 2,160 ?g/ml); and “low concentration” when AMX + MET (360 ?g/ml + 720 ?g/ml), respectively, PV + MET (360 ?g/ml + 720 ?g/ml) were used.

Growth medium together with planktonic bacteria were carefully removed and antibiotic solutions in BHI at given concentrations were gently placed in each well, in order not to induce biofilm disruption.



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