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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.

The current market scenario, latest trends and patients receiving oral therapy had more bromelain taken four times per day. No patients were developed variations on existing drugs, but many aureus(beta-lactamase producing) 0.25-0.5.

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Fleming wrote an article discussing the anaerobic bacteria present in deep wounds, which were not destroyed by the antiseptics.

His research was not accepted initially, but he continued on.

In 1922, Fleming discovered lysozyme, an enzyme with weak antibacterial properties that inhibited bacterial growth.

He also found lysozyme in fingernails, hair, saliva, skin, and tears.

In his research, Fleming found that lysozyme was effective against only a small number of non-harmful bacteria. In 1928, he started to research common staphylococcal bacteria.

An uncovered Petri dish near an open window became contaminated with mold. Fleming realized that the bacteria near the mold were dying. He isolated the mold and identified it as Penicillium genus, which he found to be effective against all Gram-positive pathogens. Gram-positive pathogens cause diseases, such as diphtheria, gonorrhea, meningitis, pneumonia, and scarlet fever. Fleming discovered that it was not the mold itself but a “juice” it had produced that had destroyed the bacteria. Later, Fleming said: “When I woke up just after dawn on September 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer.

But I suppose that was exactly what I did.” Initially, the medical community was

not

so enthusiastic about Fleming’s penicillin discovery. He also had difficulty isolating large quantities of “mold juice.” In 1940, just as Fleming was about to retire, 2 fellow scientists, Ernst Chain and Howard Florey, became interested in penicillin. Soon, they were able to mass produce penicillin for use during World War II. Fleming received many awards, including 30 honorary degrees, and most notably, the Nobel Prize in Physiology/Medicine in 1945. He was also named one of the most important people of the 20th century by Time Magazine . In terms of his

personal

life, Fleming was known as modest, patient, quiet, shy, and unemotional.

He avoided attention and was even sometimes painfully silent

around

close friends and even his wife, Sarah Marion McElroy, a nurse.

Fleming and his wife had a son, Robert, who became a general practitioner.

When she passed away after 34 years of marriage, Fleming had a very difficult time.

He lost himself in his work, spending most of his time behind closed doors in the lab. Amalia Koutsouri-Vourekas in a Greek church in London.

He died at home, of coronary thrombosis, in 1955, after suffering from stomach upset for weeks. It was said that Fleming “died as he wished: quietly, without a gradual decline in physical or mental capacity, and even without inconveniencing his physician.” Reference. Alexander Fleming (1881–1955): discoverer of penicillin.

The Canadian Paediatric Society gives permission to print single copies of this document from our website. For permission to reprint or reproduce multiple copies, please see our copyright policy. Principal

author

(s) Nicole Le Saux, Joan L Robinson; Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Acute otitis media (AOM) continues to be a common infection in young children. Milder disease, usually due to viruses or less virulent bacteria, resolves equally quickly with or without antibiotics. A bulging tympanic membrane, especially if yellow or hemorrhagic, has a high sensitivity for AOM that is likely to be bacterial in origin and is a major diagnostic criterion for AOM. Perforation of the tympanic membrane with purulent discharge similarly indicates a bacterial cause.

Immediate antibiotic treatment is recommended for children who are highly febrile (?39°C), moderately to severely systemically ill or who have very severe otalgia, or have already been significantly ill for 48 h. For all other cases, parents can be provided with a prescription for antibiotics to fill if the child does not improve in 48 h or the child can be reassessed if this occurs.

Ten days of therapy is appropriate for children - [9] There is a clinical spectrum of middle ear infections associated with the initiation and progression of infection leading to bacterial AOM. Middle ear fluid from AOM cases often harbour both viruses and bacteria; however, children who experience spontaneous resolution of AOM are likely to have viral infections alone or to have bacterial organisms that are less virulent (eg, Moraxella catarrhalis and some strains of Haemophilus influenzae ) compared with Streptococcus pneumoniae and Streptococcus pyogenes (group A streptococci [GAS]).[10] In one prospective study, 22% of children between six months and three years of age developed AOM during the first week of an upper respiratory infection, while a further 7% had myringitis without effusion.[11] Thus, the clinical presentation of AOM can vary with the stage of illness (early versus later). Also, children may or may not progress to overt bacterial AOM depending on which viruses or bacteria are present in the nasopharynx.[12] Bacteria commonly associated with AOM.

The most common bacteria causing AOM are S pneumoniae, H influenzae, M catarrhalis and (less commonly) GAS. Usually there is a single bacterial pathogen but coinfection can occur.

Studies following the routine use of the seven-valent conjugated pneumococcal vaccine (PCV7) demonstrated the increasing importance of nonvaccine type S pneumoniae and non-typable H influenzae .[13] However, more recent studies performed during the 13-valent pneumococcal vaccine era have shown lower carriage rates for S pneumoniae overall.[14] It is not yet known whether the absolute number or only the percentage of cases of AOM due to H influenzae and M catarrhalis will increase with the widespread use of the 13-valent conjugated pneumococcal vaccine (PCV13).

It has been estimated that amoxicillin 650 mg the routine use of PCV7 in Canada has decreased the incidence of AOM by 13% to 19% because nasopharyngeal colonization with vaccine-type S pneumoniae in children has been significantly reduced.[15][16] One recent study showed that AOM cases (and possibly more severe episodes) caused by S pneumoniae have decreased since the introduction of PCV13 in 2011, especially in children - [31] In a study from Finland,[29] impaired mobility of the TM was the most sensitive and specific (95% and 85%, respectively) predictor of MEE associated with AOM. A bulging TM had a high specificity (>97%) but a lower sensitivity of 51%, while a cloudy TM also had high specificity (93%) with a good sensitivity (74%) for the presence of MEE and clinical symptoms of AOM.

Other studies have also indicated that a bulging TM has a higher specificity for the presence of S pneumoniae and other bacteria, regardless of the presence of viruses, and is associated with more severe illness.[10][29] In addition to a bulging TM, it was noted that when the TM was yellow, a bacterial pathogen could be cultured 80% of the time.[30] Using a convenience sample of 264 ill children presenting to primary care with

typical

AOM symptoms, experienced otoscopists wanted to determine and validate which sign was the best predictor of AOM.

They concluded that all children with bulging TMs and only 8% of those with non-bulging TMs had AOM, making bulging the most important criteria for the diagnosis.[32] Other features, such as hemorrhagic patches or erythematous TM, had poor interobserver agreement, while erythema, opacity or air fluid levels alone – without a bulging TM – had poor

predictive

value.[29][32] Therefore, a bulging TM is a very sensitive and specific indicator for acute inflammation consistent with AOM.

Similarly, an acute perforation with purulent discharge (otorrhea) in the setting of AOM strongly supports a bacterial cause.

Although S pneumoniae is the most common cause of AOM, several studies have isolated S pyogenes in a higher percentage of patients who have spontaneous perforations compared with patients whose TMs remain intact.[33] Importantly, the drainage associated with acute symptoms of AOM and perforation should always be distinguished from otitis externa, chronic ear drainage from a previous perforation (with no middle ear inflammation) or drainage associated with a tympanostomy tube, because management for these conditions would be very different.

Clinical features not consistent with AOM are a TM with normal or slightly reduced mobility, or a non-bulging TM with or without erythema or cloudiness.

Air-fluid levels alone, without a bulging TM, are not predictive of AOM. An excellent video describing otoscopy technique and diagnostic criteria for otitis media is available at www.nejm.org/doi/full/10.1056/NEJMvcm0904397.[34] Complicated bacterial AOM at presentation. Very rarely, at initial presentation of AOM, infection has already progressed to involve adjacent structures.[35] In some cases, other associated signs or symptoms will predominate. All with spread beyond the middle ear should receive systemic antimicrobial therapy and an evaluation to consider surgical intervention and/or imaging to delineate the extent of the infection. The most common complication of AOM is acute mastoiditis. Although AOM is usually accompanied by inflammation of the mastoid air cells (including radiographic changes on computerized tomography), clinical symptoms, such as pain or swelling over the mastoid bone (behind the ear), suggest mastoiditis. Other less common but clinically important syndromes associated with AOM are acute facial (cranial nerve VII) nerve palsy, which is also associated with temporal bone inflammation, or sixth cranial nerve palsy (failure of ipsilateral eye abduction) due to petrous bone inflammation or infection (Gradenigo’s syndrome).

Additional complications may include labyrinthitis, when infection spreads to the cochlear space, venous sinus thrombosis of the transverse, lateral or sigmoid venous sinuses, and meningitis.

All children with a perforated TM who present with symptoms of AOM should be treated promptly with systemic antimicrobials and examined for associated complications. To help determine which children without perforated TMs are most likely to benefit from antimicrobial treatment for AOM, two large placebo-controlled studies involving children >6 months of age were conducted in Europe and North America. The criteria for AOM were acute symptoms of fever, ear pain or respiratory symptoms coupled with stringent objective criteria for the middle ear (MEE or TM air-fluid levels,

and

moderate or marked bulging of the TM, accompanied by marked erythema or hemorrhage, or a yellow TM).[21][22] Using these criteria, there were significantly more failures in the placebo group (35%) compared with the treatment group (19%), strongly suggesting that in children for whom the diagnosis is made using stringent criteria, treatment with antimicrobials is likely to be beneficial.

Even then, the number needed to treat to benefit one child with AOM was approximately four. When the results from the two trials for children six months to two years of age with stringent criteria were compared, failure rates with placebo were between 40% and 59% but only 14% to 25% with antimicrobials, further indicating the benefits of antimicrobial therapy in these specific clinical situations.[36] However, deciding who can be safely treated without empirical antimicrobial therapy must depend somewhat on clinical judgement but should also include objective criteria such as length and severity of illness. Children who have a mild or moderately bulging TM, and who are mildly ill, alert, responding to antipyretics, have a low-grade fever ( 90% in most jurisdictions in Canada.

[37]

- [39] Because S pneumoniae is the predominant pathogen in AOM and because it also covers GAS, empirical amoxicillin remains the drug of first choice.



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