Antibiotics May Not Be Needed After Abscess Incision and Drainage

Karla Gale, MS

April 9, 2010 — Antibiotics don't improve outcomes after incision and drainage of uncomplicated skin abscesses, new research indicates. They might prevent new abscesses at one month, however.

"We're seeing so many abscesses now," lead researcher Dr. Gillian R. Schmitz told Reuters Health. Before methicillin-resistant Staphylococcus aureus (MRSA) became so widespread, most abscess patients had diabetes or were immunocompromised, she said, "but now they're popping up all over the place in people with no traditional risk factors."

"But no one has studied best practice for treating abscesses," Dr. Schmitz added.

In a multicenter trial, she and her colleagues randomized 212 adults to receive trimethoprim-sulfamethoxazole (160 mg/800 mg) or placebo after incision and drainage of community-acquired abscesses. They instructed patients to take 2 pills twice daily for seven days. The primary outcome was treatment failure at 7 days, defined as no improvement after 2 days, development of a new separate abscess within 7 days, or worsening infection within 7 days requiring intervention.

Eighty-eight patients in the antibiotic group and 102 in the placebo group completed 7 days of follow-up; 46 and 50, respectively, returned at 30 days.

According to their March 29th online report in the Annals of Emergency Medicine, all bacterial isolates were uniformly sensitive to trimethoprim-sulfamethoxazole. Still, there was no significant difference in treatment failure rates at 7 days (17% in the antibiotic group and 26% in the placebo group, p = 0.12).

"Antibiotics don't help with resolution of infection," Dr. Schmitz said. "The most important thing is to open the wound, clean it, and get the pus out."

However, the total number of new lesions at 30 days was significantly lower in the antibiotic group: 9% vs 28% (p = 0.02).

"More study needs to be done to draw a conclusion about recurrence, because we lost so many to follow-up at 30 days," Dr. Schmitz said.

A separate trial in children with community-acquired skin abscesses found similar results. In a paper scheduled for print publication in the May issue of same journal, Dr. Myto Duong, currently at Southern Illinois University, Springfield, and associates report outcomes in 149 children after incision and drainage. The 73 children randomized to the intervention group took trimethoprim-sulfamethoxazole for 10 days (10-12 mg trimethoprim/kg/day in 2 divided doses, with a maximum of 160 mg per dose, in a liquid formulation containing 200 mg sulfamethoxazole/40 mg trimethoprim per 5 mL). The other 76 children received placebo.

The authors found no significant difference in failure rates at 10 days – 4.1% in the antibiotic group vs 5.3% in the placebo group. In addition, the antibiotic group had a significantly lower incidence of new lesions at day 10 (12.9%, vs 26.4% in the placebo group).

At 30 days, however, with 46 children in the antibiotics group and 52 in the placebo group evaluable, there was no longer a significant difference in the rate of new lesions (28.3% vs 28.8%, respectively).

"Antibiotics are not required for pediatric skin abscess resolution," Dr. Duong's group concludes, adding that further research is needed to see if antibiotics help prevent new lesions in the short term.

Both studies were limited by attrition of patients and by inclusion of subjects who were otherwise healthy, so the results can't be generalized to patients with comorbidities. In Dr. Duong's trial, medication compliance was only 66%.

In an editorial, Dr. David A. Talan of Olive View--UCLA Medical Center in Sylmar, California, states, "Antibiotics for drained simple abscesses are not required to meet the standard of care."

He told Reuters Health, "The rate of resolution of patient groups described in these studies is very high, so doctors can feel that the odds are on their side" if they forego antibiotic treatment, "and they can reassure patients there's a good chance that things will work out fine."

But, he continued, physicians should be aware of the tendency for abscesses to return, and they should advise patients to seek attention if new symptoms appear after first infection resolves.

Ann Emerg Med. Published online March 29, 2010.

 

Loneliness During the Holidays: Physician's Prize-Winning Essay

年紀大了才深覺這個問題的嚴重性！ 「我很寂寞！」 誰能解決這些老年人最切身的問題？？

其實，從扶養無依孤兒、或慰藉孤獨老人所得到的滿足感，都不亞於贏得學術大獎。

 

Megan Brooks

December 20, 2010 — It's December — "the most wonderful time of the year" — as the famous Andy Williams song goes, filled with holiday parties, family, and friends. For most of us, there's too much to do, too many people to see, not enough time.

But for some, there's too little to do, no one to see, and too much time on our hands. That's when loneliness creeps in.

Loneliness is the subject of this year's Wakley Prize–winning essay published online December 16 in The Lancet.

The annual prize honors Thomas Wakley, who founded The Lancet in 1823. The prize “seeks to exemplify the spirit of a man who was passionately committed to reforming the practice of medicine and to improving the lives of patients,” the editors of the journal note. “The prize is given to the best essay on a topic of international health importance.”

Someone to Talk to

In the essay, An Epidemic of Loneliness, Ishani Kar-Purkayastha, MD, MRCP, of the Health Protection Agency in London, United Kingdom, tells the story of Doris, an elderly widow she encountered as a junior physician on a hospital ward around the holidays.

It's 2 days before Christmas, and most patients on the hospital ward are eager to get home for Christmas; Doris is not.

She came to the hospital with a flutter in her chest that turned out to be nothing. That was 3 weeks ago. Complaint after complaint followed; they all came to nothing.

Truth is, Doris is an incredibly healthy 82-year-old with only 1 problem. She's lonely and would rather spend Christmas in the hospital than isolated, alone, at home.

Doris tells the young physician about her husband; pointing to his picture, she says, "My George, he's been gone 20 years, but it feels like yesterday we were...you know...dancing slowly together in the backyard, a glass of wine, Venus twinkling away in the sky." Doris' grown children have their own lives now, living far away.

It's time to go home, the young physician tells Doris.

Doris hesitates, turns, a tear runs down her wrinkled face. "It's just that I'm all alone," she says, "and there are so many hours in the day."

"Doctor," she asks, "can you give me a cure for loneliness?"

Thousands Like Her

"We have on our hands," Dr. Kar-Purkayastha writes, "an epidemic of loneliness, insidiously affecting those among us who have seen the ebb and flow of countless seasons, seen the world grow smaller then grow too large again." There are probably thousands like Doris.

The most difficult part, she writes, is not knowing how to solve it. For now, the young physician simply insists that Doris spend this Christmas on the ward and watches as the old woman's mood lifts instantly. At least Doris will have company this Christmas.

An editorial comment published with the essay suggests, for those "who might have a little spare time on our hands over the holidays, a visit to an older neighbor who lives alone might be just what they need to make their holiday a merry one."

Lancet. Published online December 16, 2010.

Medscape Medical News © 2010 WebMD, LLC

 

10. Nicolas Andry de Bois-Regard

這位是繼 Leeuwenhoek之後對顯微鏡下的小動物發生興趣的十七、十八世紀學者。也是骨科學祖先之一。

Nicolas Andry de Bois-Regard (1658–1742)是法國醫師兼作者，在寄生蟲學及

骨科學有貢獻； orthopedic (骨科)一字就是他首創的。他生於法國Lyon，早年學神學，不過學問廣博，三十四歲時就出版有關法文的書。1697年在Reims及巴黎取得醫師學位，再四年就取得以研究為主的Collège de France (法國學院)敎職，及Journal des savants [歐洲最早發行的科學期刊，法國革命時停刊一時期，以後逐漸失去權威性] 的編輯職位。他讀過Leeuwenhoek有關顯微鏡下微生物的文章，自己也用顯微鏡，將其所見應用在醫

學現象的說明，也引發對「自然發生」的學說開始有疑問。

1701年發表一本 “An Account of the Breeding of Worms in Human Bodies” (人體內生長的虫)，詳細描述精虫，及其他很多微生物，又解剖狗的的睪丸；也和Leeuwenhoek一樣，認為精虫是產生所有動物的起因。不過他誤以為精虫是特殊的寄生蟲之ㄧ(spermatic worms)。以為他看到的很多微生物就是天花(smallpox)及其他疾病的病原 [原則上很正確]，對「自然發生」學說質疑。他的書寫的平實易懂，也是教育大眾的，很快就被接受，成為這方面的標準教科書。1724年他成為巴黎醫學學院(Faculté de Médecine de Paris)院長。

1741年他在骨科學方面出書，書名是Orthopédie。這個新名詞(希臘文ortho=straight=直的；pais=小孩；意思就是要矯正小孩不正常的骨格發育)，一直用到現在。他的書封面畫了主幹歪曲的幼樹，用繩子被綁在一根直柱用以矯直，象徵骨科作業，在很多機構被用為骨科學的象徵；1975年法國哲學家Michel Foucault的書Discipline and punish還用這圖片。可見他當時在學術界的份量。

 

借這兩篇，也吐不完心中的悶氣啊！！

台灣選民的思考能力，為什麼如此薄弱?!  馬桶政府的奧步被揭穿了，恐怕選民還是、、、

 

<李筱峰專欄>烏鴉不快樂

「老師，你快樂嗎？」有學生這樣問我。

「那麼快樂幹什麼？」我回答。

學生噗嗤而笑，反問：「哪有人不希望自己快樂的？」

我解釋，當然人人都應該快樂，這正是每位政治家、教育家努力的目標。但身為知識份子，不該滿足於現狀，就不可能事事快樂。胡適說過：「言論的自由可以鼓勵人人肯說『憂於未形，恐於未熾』的正論危言，來替代小人們天天歌功頌德、鼓吹昇平的濫調。」其中所謂「憂於未形，恐於未熾」（在事態還未形成、還未嚴重之前就憂心戒慎）雖不必要求於眾人，但是以天下為己任的知識份子，應有如此胸懷與責任。這就是范仲淹所言「先天下之憂而憂，後天下之樂而樂」吧！中國宋朝范仲淹因上書直諫而遭貶抑，友人梅聖俞寫一篇〈靈烏賦〉勸他勿做惹人厭的烏鴉，要做討人愛的鳳凰。范不以為然，也寫一〈靈烏賦〉，仿烏鴉口吻表達其理想與抱負。這篇〈靈烏賦〉後來給胡適寫下〈老鴉〉的靈感，自比一隻「不能呢呢喃喃討人家歡喜」的老烏鴉。我曾深受感動，也經常以烏鴉自許。

五都選後，我這隻烏鴉快得憂鬱症了。因為眼前的社會病態，豈止「未形」，豈止「未熾」？簡直病入膏肓！

這次五都選舉，雖然民進黨只拿下二都，但有人以民進黨總得票數多於國民黨四十萬票，認為沒有選輸。但在我看來，輸贏都是其次，我憂心的是以下現象：

台北市政府在選前數月爆發新生高架橋弊案，貪污數字偌大，被起訴的官員已擴及郝龍斌身旁；「花博」報價高出市價數十倍甚至百倍，也一一被昭彰，花博成為「亂花錢博覽會」。出此重大弊案，結果郝龍斌不僅順利當選連任，還贏得七十九萬多票。其對手蘇貞昌弊絕風清（從屏東到台北主政期間，不許其弟在其轄區內做生意）且政績卓著，有目共睹，卻以十七萬票的落差敗選。此事非同小可，這表示台灣的首善之都，有多數選民不在乎郝市府貪贓枉法。若問這七十九萬選民，是否在乎扁珍家族的「海角七億」，則各個必成「反貪」先鋒。如此以立場論是非，等於不講是非，台灣危矣！

投票前夕發生槍擊案，案發當初兇手透露係因與國民黨候選人陳鴻源家族的土地糾紛。這個初步的「黑金」資訊，不難令選民體認陳家的背景，正常選民都應該會聞之謹慎，望之卻步，沒想到陳鴻源卻反而高票當選，大受肯定。選民的價值觀念如此錯亂！夫復何言？

槍擊案發生，有正常思考力的人都可以判斷，不管行兇動機如何，都與民進黨無關。但經過國民黨政客的栽贓操弄，竟然有那麼多選民聽信其謠言，而用選票「制裁」民進黨，終至選情翻盤。台灣民眾思考力竟薄弱至此！林肯說過：「選票比槍彈的力量還大。」看來在台灣剛好相反，這個國家危矣！

楊秋興違背初選前「任何一方出線，願無條件輔選」的承諾而參選，進而否定自己過去的立場，莫名其妙向馬英九道歉輸誠。他雖然終於落選，但我仍訝異他還能獲得四十多萬票。這四十多萬人果真認為政治人物背信、當變色龍沒有關係嗎？

以上選舉行為顯示出台灣社會價值錯亂、是非不明、民智薄弱。社會病態至此，我實在快樂不起來！台灣人睡了四百年，還喚不醒。我雖然不至於像「心煩慮亂，不知所從」的屈原那樣投江死諫，但是，在風雨如晦之時，真的「夜聞風雨之聲，難安蓆枕」！

（作者李筱峰現任國立台北教育大學台灣文化研究所教授，http://www.jimlee.org.tw）

曹長青專欄>「中國時報」的「假新聞」

最近，中國時報資深記者（也是中級主管）黃哲斌辭職事件引起很大反響，他的辭職信在網上廣泛流傳，「美國之音」等媒體也對這個事件做了報導。

一個記者辭職，怎麼會產生如此影響？因為他是抗議中時等刊登「造假新聞」而辭職。所謂造假，是馬英九政府或企業花大錢，把他們的廣告宣傳作為新聞來發表（稱為「業配新聞」）而欺騙讀者。黃哲斌說，在中國時報，「新聞變成論字計價的商品」，馬政府的公關稿不僅佔據了新聞版面，而且還被交代「一個字都不能刪」。

黃哲斌披露說，在「花博、ＥＣＦＡ、國光石化」等專案上，馬政府甚至連廣告都免了，在中國時報上「直接砸錢買新聞」。這位資深記者憤怒地說，「這是一種最最混蛋加三級的媒體控制。」他所以辭職，因不願再做這個「媒體欺騙」的同謀。他認為，「業配新聞是欺瞞讀者的，違反專業倫理的，是破壞社會信賴的怪物。」

媒體夥同政府欺騙公眾，馬英九上台後更加刺眼。黃哲斌的同事在網上回應說「你說出了我（和其他同事）的心聲。」另一位前無線電視台新聞記者說，他「每天至少說兩次謊言，每天說給幾百萬人聽！」美國之音報導說，「前些時候，聯合報記者朱淑娟也因為業界現象而辭職。」朱作為獨立記者後，最近一舉獲得曾虛白報導獎等三項新聞大獎。

國民黨利用媒體給民眾洗腦有漫長的歷史，即使台灣政黨輪替後，國民黨仍熱中此道。黃哲斌辭職信發表後，前「中視」新聞企劃室主管劉蕙苓撰文說，她也是因抗議這種「假新聞」而辭職的。她回憶說，二○○四年總統大選發生三一九槍擊案後，她所服務的中視「被國民黨要求去錄製多場的座談會」，做成專題節目。電視台高層告訴她，「黨沒有叫我們白做，他們是有付錢的！」簡直就是明火執仗地花錢買新聞，製造假新聞。

這位前中視主管痛苦地說：國民黨的「業配」最難做，因為它是中視的「大老闆」，任何一個黨務主管似乎都可以對中視的人呼來喚去。當時，他們私下稱自己就像「奴才」！

美國之音在報導這個事件時，文內標題是：媒體失格，為錢自毀貞操；並引述黃哲斌的話說，台灣媒體受到商業和政治的過多干擾，記者們被迫喪失職業道德與操守。黃哲斌說，有次澳門賭場請中時等記者，「包吃包喝包住包女人，只要寫篇豪華賭場見聞即可，我還是咬著牙拒絕了，一位相熟的同業，三天兩夜帶了一打保險套。」

「中國時報」等媒體的這種「業配新聞」，幾乎要跟對岸共產黨媒體的「有償新聞」比肩了。當今許多中國記者用報導新聞的形式，寫宣傳歌頌企業或個人的稿件，對方就要付費，這被稱為「潛規則」，即不成文的規定。報紙編輯甚至公開賣版面，電視把廣告變成新聞播放；連記者在產品記者會上舉個手提問，企業都要付費（因活躍了氣氛）。很多中國記者都因此腰纏萬貫，有目擊者說，在《人民日報》的記者停車場，一排排幾乎全是高檔車。

「中國時報」被親北京商人買去後，辦報方針特別強調兩岸是一家人。現在從「業配新聞」和對岸「有償新聞」的遙相呼應來看，還真有點「不分彼此」了，快要「假成一家」了。「中國時報」真是越來越「中國」。（作者曹長青為獨立評論員，http://caochangqing.com）

CDC Issues 2010 Treatment Guidelines for Sexually Transmitted Diseases

Laurie Barclay, MD

December 17, 2010 — The US Centers for Disease Control and Prevention (CDC) has issued updated Sexually Transmitted Diseases (STDs) Treatment Guidelines, published in the December 17 issue of the Morbidity and Mortality Weekly Report.

"The term [STDs] is used to refer to a variety of clinical syndromes caused by pathogens that can be acquired and transmitted through sexual activity," write Kimberly A. Workowski, MD, from the Division of STD Prevention National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, and colleagues. "Physicians and other health-care providers play a critical role in preventing and treating STDs. These guidelines for the treatment of STDs are intended to assist with that effort."

Estimated annual US prevalence of STD infections is 19 million. Without treatment, complications of STDs may include infertility and heightened risk for HIV infection. The present guidelines represent an update of CDC's 2006 recommendations, based on consultation with a group of experts knowledgeable in the area of STDs who were convened in Atlanta on April 18 to 30, 2009.

These guidelines were developed to offer recommendations for the treatment of persons who have or who are at risk for STDs, including human papillomavirus virus (HPV) and gonorrhoea, with updated information regarding the most effective treatment regimens, screening strategies, prevention, and vaccination schedules.

Prevention and control of STDs are based on 5 major strategies:

• educating and counseling persons at risk on strategies to reduce risk for STDs by changing sexual behaviors and using recommended prevention services;


• diagnosing asymptomatic infected persons and symptomatic persons who are unlikely to obtain diagnostic and management services;


• accurately diagnosing and effectively treating and counseling persons infected with STDs;


• evaluating, treating, and counseling sex partners of persons infected with an STD; and


• pre-exposure vaccination of persons at risk for vaccine-preventable STDs.

Although HPV is the most prevalent STD, most infected individuals remain asymptomatic, and in 90% of cases, the infection resolves spontaneously within 2 years. In other cases, genital warts or cervical cancer may result, depending on the HPV strain. HPV testing can be incorporated into cervical cancer screening among women older than 30 years but is not recommended for women younger than 20 years or for men.

One of the most effective methods of preventing HPV transmission is preexposure vaccination. To prevent cervical precancerous lesions and cancer, 2 types of HPV vaccines are licensed for females aged 9 through 26 years: bivalent HPV vaccine (Cervarix; GlaxoSmithKline) and quadrivalent HPV vaccine (Gardasil; Merck), which also prevents genital warts.

Routine vaccination with either bivalent or quadrivalent HPV vaccine is recommended for girls aged 11 or 12 years, and catch-up vaccination is recommended for females aged 13 through 26 years. Males aged 9 through 26 years may also be vaccinated with quadrivalent HPV vaccine to prevent genital warts.

Reported rates of gonorrhea are at the lowest recorded in US history, but bacterial resistance has developed and is increasing to fluoroquinolones and other antimicrobial classes recommended for treatment of Neisseria gonorrhoeae. The current recommended treatment for gonorrhea is cephalosporins, which are still effective among patients in the United States, but Southeast Asia has experienced treatment failures with oral cephalosporins. Based on previous experience with antibiotic-resistant gonorrhea, the CDC anticipates that resistant strains may spread to the United States, and therefore offers updated treatment recommendations in the 2010 guidelines.

For urogenital gonorrheal infection, the new recommendations are for ceftriaxone 250 mg intramuscularly or cefixime 400 mg orally. Treatment with azithromycin or doxycycline is recommended to cover the likelihood of coinfection with Chlamydia trachomatis in patients with gonorrhoeal infection.

Azithromycin in 1 dose has also been shown to be clinically effective for treatment of chlamydial infections in pregnancy. Pregnant women should be tested again for chlamydia 3 weeks after treatment, and women treated in the first trimester should be tested again 3 months later. Annual screening for chlamydia infection is recommended for sexually active women beginning at age 25 years or younger, using nucleic acid amplification samples from the urine, vagina, or endocervix.

Updated information and recommendations in the new guidelines also include the following:

• expanded diagnostic evaluation for cervicitis, including testing for C trachomatis and N gonorrhoeae by nucleic acid amplification, and testing for bacterial vaginosis (BV) and trichomoniasis;


• new treatment recommendations for BV (metronidazole 500 mg orally twice a day for 7 days, or metronidazole gel 0.75%, 1 full applicator [5 g] intravaginally, once a day for 5 days, or clindamycin cream 2%, 1 full applicator [5 g] intravaginally, at bedtime for 7 days) and for genital warts (including waiting for spontaneous resolution, or podofilox 0.5% solution or gel, or imiquimod 5% cream, or sinecatechins 15% ointment);


• the role of Mycoplasma genitalium and trichomoniasis in urethritis/cervicitis and treatment-related implications (for nongonococcal urethritis not caused by C trachomatis, single-dose azithromycin or doxycycline for 7 days, followed by single-dose metronidazole or tinidazole if symptoms persist);


• lymphogranuloma venereum proctocolitis among men who have sex with men;


• criteria for spinal fluid examination to evaluate for neurosyphilis;


• emergence of azithromycin-resistant Treponema pallidum — azithromycin should not be routinely used to treat syphilis, which is still best treated with penicillin or with a 14-day course of doxycycline in penicillin-allergic patients;


• recognition of an increased role for sexual transmission of hepatitis C, especially in individuals coinfected with HIV;


• diagnostic evaluation after sexual assault by an experienced clinician in a manner that minimizes further trauma, with the decision to obtain genital or other specimens for STD diagnosis to be made on an individual basis;


• prophylaxis and treatment after sexual assault including postexposure hepatitis B vaccination without hepatitis B immune globulin, and one-time antibiotic treatment with ceftriaxone or cefixime, metronidazole, and azithromycin; and


• STD prevention approaches, including abstinence and reduction of number of sex partners, preexposure vaccination (including against hepatitis A and B), barrier methods, male circumcision, and high-intensity behavioral counseling for all sexually active adolescents and for adults at increased risk for STDs and HIV.

"These recommendations should be regarded as a source of clinical guidance and not prescriptive standards; health-care providers should always consider the clinical circumstances of each person in the context of local disease prevalence," the guidelines authors write. "They are applicable to various patient-care settings, including family-planning clinics, private physicians' offices, managed care organizations, and other primary-care facilities. These guidelines focus on the treatment and counseling of individual patients and do not address other community services and interventions that are essential to STD/human immunodeficiency virus (HIV) prevention efforts."

Morb Mortal Wkly Rep. 2010;59:1-109.

Medscape Medical News © 2010 WebMD, LLC

 

Doripenem: A New Carbapenem Antibiotic

Elias B. Chahine; Mary J. Ferrill; Mara N. Poulakos

Posted: 12/06/2010; American Journal of Health-System Pharmacy. 2010;67(23):2015-2024. © 2010 American Society of Health-System Pharmacists, Inc.

Abstract and Introduction

Abstract

Purpose. The chemistry, pharmacology, antimicrobial activity, pharmacokinetics, pharmacodynamics, efficacy and safety in humans, and formulary considerations of doripenem are reviewed.
Summary. Doripenem, a member of the β-lactam class of antibiotics, is the newest addition to the carbapenems. It exhibits concentration-independent bactericidal activity against gram-positive bacteria; enteric and nonenteric gram-negative bacteria, including extended-spectrum β-lactamase-producing strains; and anaerobic pathogens. Doripenem was found to be noninferior to meropenem in the treatment of complicated intraabdominal infections and noninferior to levofloxacin in the treatment of complicated urinary tract infections including pyelonephritis and was granted marketing approval by the Food and Drug Administration for these two indications. Doripenem was also found to be noninferior to imipenem in the treatment of ventilator-associated pneumonia and noninferior to piperacillin–tazobactam in the treatment of hospital-acquired pneumonia. It has a favorable safety profile, with gastrointestinal complaints and headache being the most common adverse effects and allergic reactions the most serious adverse effects. Doripenem has a relatively low potential to induce seizures. The only known clinically relevant drug interaction is that coadministration with valproic acid may result in reductions of valproic acid serum concentrations. As with most renally eliminated antibiotics, the dose of doripenem should be adjusted according to kidney function.
Conclusion. Doripenem is an injectable carbapenem antibiotic with a spectrum of activity comparable to that of imipenem and meropenem. Its safety is similar to that of other carbapenems.

[和 imipenem or meropenem 差不多就是了！]

Treatment for Acute Hematogenous Osteomyelitis of Childhood

Short- versus Long-term Antimicrobial Treatment for Acute Hematogenous Osteomyelitis of Childhood: Prospective, Randomized Trial on 131 Culture-positive Cases

Heikki Peltola, MD; Markus Pääkkönen, MD; Pentti Kallio, MD, PhD; Markku J. T. Kallio, MD

Posted: 12/06/2010; Pediatr Infect Dis J. 2010;29(12):1123-1128. © 2010 Lippincott Williams & Wilkins

Abstract and Introduction

Abstract

Background: Considerable uncertainty exists on the optimal duration of antimicrobials for acute hematogenous osteomyelitis (AHOM) in children. Often they are administered for 1 to 2 months, the first 1 to 2 weeks intravenously, and decompressive surgery is usually added. No prospective, randomized, sufficiently powered comparative trial has been available.

Methods: Children aged 3 months to 15 years with culture-positive AHOM were randomly assigned to receive clindamycin or a first-generation cephalosporin for 20 or 30 days, including an intravenous phase for the first 2 to 4 days. Surgery was kept at minimum. Illness was monitored with preset criteria. Antimicrobial was discontinued once most signs had subsided and serum C-reactive protein decreased ≤20 mg/L. The primary end point was full recovery without need for further antimicrobial therapy because of an osteoarticular indication during the 12 months after the primary therapy.

Results: Of the 131 cases, 18% also involved the adjacent joint. Staphylococcus aureus caused 89% of cases, and all strains were methicillin susceptible. The median duration of treatment was 20 days for 67 children, and 30 days for 64 children. Most children underwent only the diagnostic percutaneous aspiration or drilling, and 24% had no surgery. Except for 1 mild sequela in both treatment groups, all patients recovered entirely.

Conclusions: Most cases of childhood AHOM can be treated for 20 days, including a short period intravenously, with large doses of a well-absorbed antimicrobial such as clindamycin or a first-generation cephalosporin, provided the clinical response is good and C-reactive protein normalizes within 7 to 10 days. Extensive surgery is rarely needed.

 

 

「中華民國」是非法佔據台灣的流亡政府

學者批國史館 沒有台灣意識

〔記者林曉雲／台北報導〕國史館舉辦「民國百人」票選活動，將中國已故領導人毛澤東、鄧小平等人列入成為票選最佩服的人物，引發爭議。國立台北教育大學台灣文化研究所教授李筱峰直批，國史館「太荒唐」，他表示，國史館會把鄧小平、毛澤東等人放入民國百年名人誌的候選名單中，凸顯了國史館完全不是以台灣主體意識作為立足點，連慶祝哪一個國家百年都搞不清楚，所以出現如此荒謬名單與票選。

李筱峰並質疑，一九一二年開國時的中華民國，其範圍是所謂的「秋海棠」，並不包括台灣；但一九四九年以後掛名「中華民國」的範圍卻只有台灣，而沒有「秋海棠」，國號雖然相同，但範圍剛好顛倒過來，這是世界絕無僅有的奇觀，也正是台灣尷尬的處境，事實上，中華民國早在一九四九年就消失了，不知道要慶祝哪個百年？

政大台灣史研究所教授薛化元也表示，中華民國建國與台灣無關，台灣那時候是日治時期，就學術立場來看，國史館若是定義在慶祝中華民國百年名人誌，那麼把中華民國統治大陸時期的人物列入可以理解，國民黨被共產黨打敗才來到台灣，因此把一九四九年之前的共產黨重要人物列入也算合理，但絕不能把一九四九年之後的中國人物列入。

 

 

Refractory lymphoma可以用 Brentuximab治療

Brentuximab shows :Amazing" responses in refractory lymphoma

Zosia Chustecka

December 8, 2010 (Orlando, Florida) — The experimental agent brentuximab vedotin has shown "amazing responses" in patients with resistant and refractory Hodgkin's lymphoma, researchers reported here at the American Society of Hematology (ASH) 52nd Annual Meeting. It offers hope for patients who have no other options and a poor prognosis, they said.

Brentuximab represents "a big breakthrough for this patient population," said Ginna Laport, MD, associate professor of medicine at Stanford University Medical Center, California.

"This is a very exciting drug for Hodgkin's lymphoma," she told journalists at an ASH press briefing.

Lymphoma expert Andre Goy, MD, from the John Thuerer Cancer Center at Hackensack University in New Jersey, agreed.

Dr. Goy told Medscape Medical News that the responses that have been seen in refractory patients have been "very impressive," and he predicted that even better responses will be seen with the drug in less advanced patients. In the future, he said, it could be used up front in combination with chemotherapy, which could be "phenomenal."

The drug is being developed by Seattle Genetics and Millennium/Takeda, and the companies plan to apply for approval in early 2011.

Dr. Goy praised the researchers for their persistence in developing the drug; there have been several previous frustrating failed attempts.

The product is an antibody–drug conjugate. The antibody targets CD30, a protein expressed on cancer cells in Hodgkin's lymphoma. It is also expressed in anaplastic large cell lymphoma, an aggressive type of T cell non-Hodgkin's lymphoma, which also responds to treatment with this drug.

The antibody latches onto the CD30 expressed on the cancer cell surface, and then delivers the attached drug (monomethyl auristatin E), which is toxic to the cell. It is this double action that led to success; previous attempts using just antibodies had been unsuccessful.

New Hope for Patients

The indication of refractory and resistant Hodgkin's lymphoma has been allocated fast-track approval by the US Food and Drug Administration (FDA), because these patients have no other treatment options.

These patients tend to be young; average age at diagnosis is about 30 years. Once they have failed autologous stem cell transplantation and several lines of chemotherapy, there is really little else that remains, and survival then is only about 2 and a half years, explained Anas Younes, MD, from the University of Texas M.D. Anderson Cancer Center in Houston. He was involved in the clinical trials of brentuximab, and headed a recently published phase 1 study (N Engl J Med. 2010;363:1812-1821).

This new drug offers hope for these patients, he said. Hodgkin's lymphoma is a highly curable disease, he noted, but about 20% of patients become refractory or resistant to further treatment.

The responses to brentuximab that have been reported "are amazing with a single agent in such a refractory patient population," Dr. Younes told Medscape Medical News.

New details from 2 phase 2 clinical trials, which will be used for the approval application, were presented at the ASH meeting and highlighted in the final Best of ASH session. Top-line results were released last month, and reported by Medscape Medical News at the time.

Dramatic Response Rates

Dr. Robert Chen

The results in refractory and resistant Hodgkin's lymphoma were reported by Robert Chen, MD, assistant professor at the City of Hope National Medical Center in Duarte, California.

They come from a single-group multicenter study of 102 patients, all of whom had failed autologous stem cell transplantation and a median of 4 chemotherapy regimens (range, 1 to 13). The median age of patients was 31 years (range, 15 to 77 years).

Brentuximab 1.8 mg/kg was administered as a 30-minute outpatient intravenous infusion once every 3 weeks, up to 16 cycles of therapy (median, 9 cycles).

Responses were "dramatic," Dr. Chen said. The objective response rate was 75%, and tumor reduction was demonstrated in 94 patients (96%). Around one third of patients (34%) achieved complete remission; the median duration for complete remission has not yet been reached.

Adverse effects were "very manageable," Dr. Chen said. The most common were peripheral sensory neuropathy (reported by 43% of patients), fatigue (40%), nausea (35%), neutropenia (19%), diarrhea (18%), and pyrexia (16%). Most were grade 1 or 2. The neuropathy resolved once the drug was discontinued in most patients, he said. It was discontinued in 10% of patients because of neuropathy and another 9% had a dose reduction because of this adverse effect.

Kristie Blum, MD, from Ohio State University in Columbus, highlighted these brentuximab data in an educational session on future treatments for Hodgkin's lymphoma, alongside other new agents that are being investigated in this disease. These include the experimental agent panobinostat (Novartis), everolimus, and lenalidomide.

"Brentuximab is the one that is furthest along and it has shown the highest response rates so far," she told Medscape Medical News. Some of the other new drugs have responses that are not as high but are very durable, with patients remaining in remission for 2 to 3 years so far.

Dr. Blum highlighted the problem of peripheral neuropathy with brentuximab, and said that she has had patients who have had to discontinue the drug because of this adverse effect.

Results in Anaplastic Large Cell Lymphoma

Results in refractory and resistant anaplastic large cell lymphoma were presented at the meeting by Andrei Shustov, MD, from the Fred Hutchinson Cancer Research Center, University of Washington, Seattle. They come from a phase 2 study of 58 patients who had failed on a median of 2 chemotherapy regimens (range, 1 to 6); 44% of patients had also undergone radiation.

Dr. Shustov noted that the only FDA-approved therapy for these patients is pralatrexate (Folotyn), which has shown an objective response rate of 27% and complete remission in 8% of patients.

In this trial, brentuximab treatment resulted in an objective response rate of 86% and complete remission in 54%. This complete remission rate is "remarkable," said Robert Hromas, MD, from the University of New Mexico, Albuquerque, who highlighted these results in the Best of ASH session at the end of the meeting.

"All but 1 patient had shrinkage of their tumor," Dr. Shustov reported, adding that this result (in 57 of 58 patients) was confirmed by an independent review. The median duration of response has not been reached, he added.

The adverse effects were manageable, he said. The median time to onset of peripheral neuropathy was 16 weeks, and the neuropathy was reversible in about half of patients, he said.

All the brentuximab studies were funded by the manufacturer.

American Society of Hematology (ASH) 52nd Annual Meeting: Abstract 283, presented December 6, 2010; Abstract 961, presented December 7, 2010.

Medscape Medical News © 2010 WebMD, LLC
Send comments and news tips to news@medscape.net.

Ceftraroline, a 5th. generation cephalosporin

FDA approves Ceftraroline for CABP and cSSSI

Fran Lowry

September 8, 2010 — The Anti-Infective Drugs Advisory Committee of the US Food and Drug Administration (FDA) has heartily endorsed ceftaroline (Cerexa Inc) for the treatment of community-acquired bacterial pneumonia (CABP) and complicated skin and skin structure infections (cSSSI).

At yesterday's meeting, in the morning session, the committee voted 21 to 0 in favor of ceftaroline for CABP, and in the afternoon, a slightly smaller committee voted 18 to 0 in favor of its use for cSSSI. There were no abstentions.

The committee was warm in its praise of the sponsor and the data it presented for both indications.

Ceftaroline is a beta-lactam of the cephalosporin class of antimicrobials with activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria associated with skin and respiratory infections. It also has activity against methicillin-resistant Staphylococcus aureus and Streptococcus pneumonia.

Members of the committee said they found it very easy to cast their affirmative votes when asked whether the sponsor had demonstrated safety and efficacy in CABP and cSSSI.

CABP Indication

"I thought this was a relatively easy decision to make," commented Dean Follmann, MD, from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, Bethesda, Maryland, in explaining his yes vote for the CABP indication.

"It was a very easy decision to make. The noninferiority margin was preserved in instances. In fact, it seemed that cefteroline was strong enough to perhaps star in its own Old Spice commercial," said committee chair Thomas Moore, MD, from Ochsner Health System, New Orleans, Louisiana.

Erica Brittain, PhD, from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, said she wished all noninferiority trials were this easy to interpret, adding that she was "very impressed that there were hints of superiority all over the place" for ceftaroline.

John E. Bennett, MD, also from the National Institutes of Health, congratulated the manufacturer for a "well-designed, carefully conducted and conservatively analyzed study" and said he was impressed by the quality of the data.

However, he voiced one concern about the generalizability of the data supporting the CABP indication, which were collected in an eastern European population, to patients in the United States. "This population seems to be less sick than patients in this country, but apparently it's impossible to conduct these kinds of studies in the United States. I believe they tried, but I'm not completely assured that we could extrapolate those results to our patients."

One of the pediatricians on the panel, Sheldon L. Kaplan, MD, from Baylor College of Medicine and Texas Children's Hospital, Houston, said he was looking forward to the pediatric studies that the sponsor had promised. "I think this is a potentially fabulous drug for pediatric patients — one that will be very helpful to us — and I hope that we will have much more information on penetration into the [cerebrospinal fluid] because that is always a concern in patients who have pneumococcal bacteremia in particular."

cSSSI Indication

The committee was equally positive about ceftaroline for cSSSI, although some members voiced minor concerns.

Peter Katona, MD, from the David Geffen School of Medicine at the University of California–Los Angeles, said, "I have to admit, I have a weak spot for anything that could replace 2 drugs with 1 drug, which I hope is something that this drug could eventually do."

"I'm impressed at how difficult it is to get a homogeneous group of patients with skin and soft tissue [infections] together," commented Kent A. Sepkowitz, MD, from Memorial Sloan-Kettering Cancer Center, New York City. "The sponsor did a decent job."

Dr. Moore said that cefteroline is now the poster child of how to get through the new FDA endpoints. He also thanked the FDA for their hard work "in crunching the data," adding that this emphasized the effectiveness of the drug.

Medscape Medical News © 2010 WebMD, LLC

[Ceftaroline is a broad-spectrum cephalosporin. Ceftaroline has the ability to bind to penicillin-binding protein (PBP) 2a , an MRSA-specific PBP that has low affinity for most other β-lactam antibacterials. The high binding affinity of ceftaroline to PBP 2a (median inhibitory concentration 0.90 μg/mL) correlates well with its low minimum inhibitory concentration for MRSA. Ceftaroline is active in vitro against Gram-positive cocci, including MRSA, meticillin-resistant Staphylococcus epidermidis, penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant Enterococcus faecalis (not E. faecium). The broad-spectrum activity of ceftaroline includes many Gram-negative pathogens but does not extend to extended-spectrum β-lactamase-producing or AmpC-derepressed Enterobacteriaceae or most nonfermentative Gram-negative bacilli. Ceftaroline demonstrates limited activity against anaerobes such as Bacteroides fragilis and non-fragilis Bacteroides spp. Limited data show that ceftaroline has a low propensity to select for resistant subpopulations.

Ceftaroline fosamil (prodrug) is rapidly converted by plasma phosphatases to active ceftaroline. For multiple intravenous doses of 600 mg given over 1 h every 12 hours for 14 days, the maximum plasma concentration was 19.0 μg/mL and 21.0 μg/mL for first and last dose, respectively. Ceftaroline has a volume of distribution of 0.37 L /kg ( 28.3 L ), low protein binding (<20%) and a serum half-life of 2.6 hours. No drug accumulation occurs with multiple doses and elimination occurs primarily through renal excretion (49.6%). Based on Monte Carlo simulations, dosage adjustment is recommended for patients with moderate renal impairment (creatinine clearance 30–50 mL/min); no adjustment is needed for mild renal impairment.

Currently, limited clinical trial data are available for ceftaroline. A phase II study randomized 100 patients with cSSSI to intravenous ceftaroline 600 mg every 12 hours or intravenous vancomycin 1 g every 12 hours with or without intravenous aztreonam 1 g every 8 hours (standard therapy) for 7–14 days. Clinical cure rates were 96.7% for ceftaroline compared with 88.9% for standard therapy. Adverse events were similar between groups and generally mild in nature. In a phase III trial, 702 patients with cSSSI were randomized to ceftaroline 600 mg or vancomycin 1 g plus aztreonam 1 g, each administered intravenously every 12 hours for 5–14 days. Ceftaroline was noninferior to vancomycin plus aztreonam in treating cSSSI caused by both Gram-positive and -negative pathogens. Adverse event rates were similar between groups.

Ceftaroline is well tolerated, which is consistent with the good safety and tolerability profile of the cephalosporin class. In summary, ceftaroline is a promising treatment for cSSSI and CAP, and has potential to be used as monotherapy for polymicrobial infections because of its broad-spectrum activity. Further clinical studies are needed to determine the efficacy and safety of ceftaroline, and to define its role in patient care.]

 

[Ceftaroline (INN) ( brand name Teflaro) is a fifth-generation cephalosporin antibiotic. It is notable for its activity against methicillin-resistant Staphylococcus aureus (MRSA) and Gram positive bacteria. It retains the activity of later generation cephalosporins having broad spectrum activity against Gram negative bacteria. It is currently being investigated for community-acquired pneumonia and complicated skin and skin structure infection.

Ceftaroline is being developed by Forest Laboratories, under a license from Takeda. Ceftaroline has received approval from the U.S. Food and Drug Administration for the treatment of community-acquired bacterial pneumonia and acute bacterial skin infections on October 29, 2010. In vitro studies show that it has a similar spectrum to ceftobiprole, the only other fifth-generation cephalosporin to date, although no head to head clinical trials have been conducted. Currently, ceftaroline and ceftobiprole are on an unnamed subclass of cephalosporins by the Clinical and Laboratory Standards Institute (CLSI).]

Avian influenza A (H5N1)

Clinical course of avian influenza A(H5N1) in patients at the Persahabatan Hospital, Jakarta, Indonesia, 2005-2008.

Chest.  2010; 138(3):665-73 (ISSN: 1931-3543)

Soepandi PZ; Burhan E; Mangunnegoro H; Nawas A; Aditama TY; Partakusuma L; Isbaniah F; Ikhsan M; Swidarmoko B; Sutiyoso A; Malik S; Benamore R; Baird JK; Taylor WR
Rumah Sakit Persahabatan, Jakarta timur, Indonesia.

BACKGROUND: Limited understanding of the presentation and course of influenza A(H5N1) infection in humans hinders evidence-based management. METHODS: We reviewed the case records of patients admitted to the Persahabatan Hospital (RSP), Jakarta, Indonesia, with influenza A(H5N1) confirmed by real-time polymerase chain reaction. RESULTS: Twenty-two previously well patients, aged 3 to 47 years (median 24.5 years), were identified. All attended a clinic or hospital after a median of 2 days of illness (range 0-7). Times to first dose of oseltamivir (three died before receiving oseltamivir) were 2 to 12 days (median 7 days), administered mostly (n = 15) at RSP. Nineteen patients required mechanical ventilation. Deaths numbered 18 (case fatality = 82%) occurring within hours to 6 days of RSP admission, corresponding to 6 to 16 days of illness. Admission hyperglycemia ( >or= 140 mg/dL), unrelated to steroids or known underlying diabetes mellitus, and elevated D-dimer levels (0.81-5.2 mg/L, upper limit of normal < 0.5 mg/L) were present in 14/21 (67%) and 20/21 (95%) patients, respectively. Fibrinogen concentrations were mostly low/normal at 129.9 to 517.9 mg/dL (median 241.1, normal 200-400 mg/dL), whereas C-reactive protein (9/11) and ferritin (6/8) levels were increased. Risk factors for death (univariate analysis) included: (1) increased D-dimers, (2) hyperglycema, (3) increased urea, (4) more extensive chest radiograph shadowing, and (5) lower admission oxygen saturation. CONCLUSIONS: Early diagnosis and effective treatment of human influenza A(H5N1) infection remains challenging. Most patients were referred late with advanced disease. Oseltamivir had limited clinical impact. Elevated D-dimer levels, consistent with fibrinolysis, and hyperglycemia warrant more research to determine their underlying mechanisms and optimal treatment.

[D-dimer is a fibrin degradation product, a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two crosslinked D fragments of the fibrinogen protein.

D-dimer concentration may be determined by a blood test to help diagnose thrombosis. Since its introduction in the 1990s, it has become an important test performed in patients suspected of thrombotic disorders. While a negative result practically rules out thrombosis, a positive result can indicate thrombosis but does not rule out other potential causes. Its main use, therefore, is to exclude thromboembolic disease where the probability is low. In addition, it is used in the diagnosis of the blood disorder disseminated intravascular coagulation.]

A new molecular assay for C. difficile

November 23, 2010 (San Jose, California) — A self-contained molecular assay for Clostridium difficile allows sensitive and specific identification within 24 hours, and detects the toxin A gene (tcdA) in addition to the toxin B gene (tcdB).

C difficile–associated diarrhea is on the rise in both hospital and community settings, and with it comes an increased need for a rapid diagnostic test to identify the presence of C difficile and help guide treatment, noted Brianne Couturier, PhD, from the ARUP Institute for Clinical Experimental Pathology at the University of Utah School of Medicine, Salt Lake City, during her poster presentation here at the Association for Molecular Pathology 2010 Annual Meeting.

Dr. Couturier presented the results of a new molecular assay that rapidly detects tcdA, along with the traditional tcdB of C difficile, which is considered "essential for virulence," Dr. Couturier said.

She said the results of her study might reopen the debate on the importance of toxin A in clinical disease that many thought had been settled a decade ago.

The study involved 40 clinical isolates from 20 species of C difficile and non–C difficile samples. The researchers compared the abilities of 2 assays to recognize various C difficile strain types and toxin classes and to determine crossreactivity with other Clostridium spp.: the illumigene C difficile assay (Meridian Biosciences), which targets the highly conserved 5′ region of tcdA, using LAMP (loop-mediated isothermal amplification), and tcdB; and the GeneOhm C difficile assay (BD Diagnostics).

The technology had not been cleared by the US Food and Drug Administration at the time the Utah team submitted their study abstract, but subsequently was cleared.

Dr. Couturier explained to Medscape Medical News that although tcdA is present, it is not necessarily upregulated to produce all of the toxin proteins. "The majority of toxins in [toxin] A strains are due to large deletions in the 3′ end of the gene; however, the 5′ end is highly conserved," which is where the assay primer attaches. "Even if it is a toxin A–negative strain, the illumigene assay is able to pick it up."

She said the 2 assays were 100% concordant in identifying the B⁺ strains of C difficile. The illumigene assay was able to detect toxin A⁺B⁺ strains of toxinotypes 0 (16 strains), III (6 strains), V (6 strains), XII (1 strain), and IX/XXIII (1 strain). It also amplified A^–B⁺ strains of toxinotypes VIII (3 strains) and X (1 strain).

As a negative control, neither assay was able to amplify 34 non–C difficile, Clostridium spp. isolates, including the closely related Clostridium sordelii (n = 3).

One of the samples was positive on the illumigene assay and negative on the GeneOhm assay. When she looked more closely, Dr. Couturier found that the sample contained 2 polytypes. "When I isolated them out, one was C difficile A⁺B⁺ and the other was Clostridium symbiosum."

Dr. Couturier prefers the illumigene assay because it is self-contained and a bit quicker. "The BD GeneOhm has the same license mechanism; however, you have to make up the master mix separately. If you don't make full runs, you're wasting reagent, whereas with the illumigene [assay], you don't waste reagents." The workflow is improved and technician time is saved.

Donna Wolk, PhD, D(ABMM), a microbiologist at the University of Arizona, Tucson, pointed out that evidence emerged several years ago to suggest that toxin B is the essential virulence factor for clinical disease caused by C difficile. Toxin A is thought to act in synergy with toxin B. The role of toxin A is still evolving, and reports are conflicting. This study suggests that "maybe the story is not over," Dr. Wolk noted.

"Researchers made an interesting disease association, and these results will require further confirmation to determine whether toxin A alone is sufficient to cause disease. The assay may be a useful tool for exploring those disease connections," she said.

The study was underwritten by Meridian Biosciences. Dr. Couturier is employed by the ARUP Institute for Clinical and Experimental Pathology at the University of Utah. Dr. Wolk has disclosed no relevant financial relationships.

Association for Molecular Pathology (AMP) 2010 Annual Meeting: Abstract ID55. Presented November 18, 2010.

Fidaxomycin better than vancomycin in treating C. difficile colitis

September 15, 2010 (Boston, Massachusetts) by Alice Goodman, — Fidaxomicin is superior to vancomycin in treating recurrences of gastrointestinal Clostridium difficile infection, according to a blinded randomized trial presented here at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

"Over 20 years, vancomycin has been the best drug for efficacy [in the treatment of C difficile infection. The problem is that the recurrence rate in sick people, like those we included in the study, is about 30%. Now we know we can prevent recurrences after vancomycin with fidaxomicin. Fidaxomicin was also superior as first-line treatment in phase 3 studies. In my view, this is a dramatic change," said Oliver A. Cornely, MD, from the University Hospital of Cologne in Germany.

Fidaxomicin is a first-in-class oral macrocyclic antibiotic developed by Optimer Pharmaceuticals. The drug has a narrow spectrum of activity against normal gut flora, with potent bactericidal activity against C difficile. It attacks the pathogenic bacteria while sparing normal protective gastrointestinal flora. In contrast, vancomycin, which is approved for this indication, and metronidazole, which is often used as treatment, suppress the growth of normal endogenous flora.

The study presented at ICAAC focused on a prespecified nested population of 178 patients with a first recurrence within 90 days of a previous episode. Patients were then randomized to receive either fidaxomicin or vancomycin. These 178 patients came from 2 randomized phase 3 trials of 1164 patients with acute C difficile infection. In both phase 3 trials, fidaxomicin was noninferior to oral vancomycin in preventing symptom recurrence within 30 days of completing 10 days of therapy.

Recurrence was defined as 3 or more unformed bowel movements in the 24 hours prior to randomization and the presence of C difficile toxin A or B in the stool within 48 hours of randomization; this definition was used in the original phase 3 trials and in the nested trial.

For 10 days, patients received oral fidaxomicin 200 mg twice daily or oral vancomycin 125 mg 4 times daily. More than 90% of both groups responded to initial therapy in the phase 3 trials.

In the nested trial, 55% were female, 53% were inpatients, and the mean age was 63 years. Among 122 evaluable patients, fidaxomicin was significantly superior to vancomycin for the primary end point of a second recurrence within 28 days (19.7% vs 35.5%; P = .045). Fidaxomicin was also significantly superior to vancomycin in preventing a second recurrence in up to 14 days (7.6% vs 27.4%; P = .003).

"Recurrences occurred later with fidaxomicin — on about day 17 compared with day 8 — for patients on vancomycin," Dr. Cornely said.

Older age is a known risk factor for recurrent C difficile, he continued. In the nested study, patients 75 years and older were 2.7 times more likely to experience a recurrence than those between 18 and 54 years of age. No difference in recurrence rate was seen between patients in the 2 age groups.

Dr. Cornely believes that an explanation for the superiority of fidaxomicin in these studies is that the healthy flora protected against the re-emergence of C difficile in patients who received the newer drug, whereas persistent spores of the bacteria remained in the gut of patients who received vancomycin.

"The subgroup analysis of initial studies suggests that fidaxomicin may be a very important tool for preventing recurrence after initial infection, but large prospective trials are needed to address that issue properly," said David M. Aronoff, MD, comoderator of the session in which Dr. Cornely presented the study results. Dr. Aronoff is assistant professor of infectious diseases at the University of Michigan in Ann Arbor.

Dr. Aronoff noted that fidaxomicin might be a good drug for first-line therapy as well. "It may be as effective as vancomycin in treating initial infection, as well as in preventing recurrence."

He said that further study is needed to determine the putative connection between the differential effects of vancomycin and fidaxomicin on the bacterial environment of the gut and whether those differential effects are causally related to the clinical effects of these drugs.

Dr. Cornely reports serving as a consultant to Optimer Pharmaceuticals, and having ties with other pharmaceutical companies, but none that make anti–C difficile drugs. Dr. Aronoff has disclosed no relevant financial relationships.

50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract L1-1305. Presented September 13, 2010.

Medscape Medical News © 2010 WebMD, LLC

26. Shiga Kiyoshi (志賀 潔)--Shigella赤痢桿菌以他的姓命名

Shigella, shiga toxin, shigellosis這些名稱就是以這位學者命名。

Shiga Kiyoshi (志賀 潔1871-1957)。日本的醫師細菌學家，發現赤痢及其毒素，細菌 屬名(genus)被命名為Shigella，毒素稱為shiga toxin，是唯一以日本人名給細菌命名者。曾任朝鮮総督府醫院長、京城(指的是南韓Seoul)醫學専門學校校長、京城帝国大學総長。末年清貧，其原因多受猜測。

明治3年生於現在的仙台市，仙台藩士之子。姓佐藤(Sato)，幼名直吉(Naokichi)，八歲時做母親娘家養子，改姓志賀，改名潔。志賀家是歷代仙台藩之藩医。在仙台讀完高中後，1892年入學帝国大學醫醫科大學（以後的東京帝国大學醫學部）。1896年畢業，進入「大日本私立衛生會傳染病研究所，師事北里柴三郎。[當時細菌學是最新的熱門科學]。1897年發生赤痢大流行，90,000人得病，後半年間全國死亡22,300人(病人死亡率24.9%)。當時以為是阿米巴引起。志賀在北里指導下，從糞便眾多細菌中發現赤痢菌，在「細菌學雑誌」發表日文的『赤痢病原研究報告第一』。1898年再用德文發表[Zentralbl f. Bakteriol , 1 Abt., XXIV (1898)]。自此赤痢菌之属名(genus)被稱為Shigella。1899年任内務省技師・傳染病研究所第一部長。

[但在1901年在德國留學時，在Hanburg的萬國自然科學學會裡，Bonn大學的W. Kruse( 1864-1943年）報告他發現了赤痢菌。志賀立即起來用德語辯駁說，他已經在四年前發現了，引起激辯，當場無法決定誰對誰錯，結果由「赤痢菌調査委員會」決定命名為Shiga-Kruse bacilli。此後曉得赤痢菌有許多種類，結果將志賀發現的設為赤痢本型菌，shigella作為屬名]。[筆者按:在科學界或任何國際場合，不會用共通語言發表溝通，是會吃虧!當時德國醫學研究成果最豐盛，英法語系的無法相較，因此醫學國際語言是德文，我們1950年代醫學基夲教育包含德文一年。六零年代以後英文已經取代為國際科學語言]。

1901到1903年間，他到柏林Paul Ehrlich之The Royal Prussian Institute for Experimental Therapy研究治療Trypanosomiaisis(原生虫疾病，會引起sleeping sickness)，研究出benzene類紅色素藥物 “Trypan Rot”(Rot = red)，和Ehrlich聯名於1904年發表；Beyer公司也出品。是發現Salvarsan化學療法的先驅。 他也曾到Heidelberg之institute for physiological chemistry工作。

1905年歸國取得醫學博士學位。他又研究脚気病，用實驗否定東大學派之細菌為病原之學說。1912年再到德國師事Paul Ehrlich。1914年和北里一起從傳染病研究所(因為無預警地被併入東大之下—日本式學派鬥爭的結果!)辭職。翌年入新創立的北里研究所（現在的北里大学）。當時有關痲瘋病的爭論，「大学派」以国際所持，認為「不考慮傳染性高低，強制隔離是落後的想法」、「痲瘋病感染和體質遺伝有關，健康人、栄養好的人不容易傳染」，「神経癩絕不會傳染」。當時任京城帝国大学総長的志賀潔在『朝鮮』一九三一年三月号刊登論文「衛生上的改良及食料営養状態的改善可以減少癩病傳染」。對此村田正太（在大阪療養所的外島保養院長）和他的老師光田健輔等「療養所派」，則主張癩病是非常危險的急性傳染病，需要絕對隔離。再利用皇室的壓力使大學派無法批判「療養所派」。1941年十一月在大阪招開的第十五次「日本癩學會」大學派最受批評。[按：沒有證據時，任何爭論都無意義。尤其是未能「學術歸學術」地討論時，各方堅持己說，學問只會退步]。

1920年（大正9年）就職慶應義塾大學醫學部教授，但同年秋轉任朝鮮総督府醫院長、京城醫學學専門學校校長。1926年（大正15年）轉任新創立的京城帝国大學（現在的韓城Seoul大學）醫學部長。1929年（昭和4年）升任其大学総長。1930年在開学記念講演「痲瘋病歴史及麻瘋病研究」。這演講內容被解釋為志賀主張痲瘋病患要割去睪丸、割除卵巢，斷種，受到痲瘋學會及醫學部教授的嚴重批判，因而任職未期滿就辭職!

1931年他回日本當北里研究所顧問。1945年東京大空襲時家財盡失疏散到仙台。1957年（昭和32年）老衰死亡。由仙台市舉行市葬。葬在青葉區北山輪王寺。

他有哈佛榮譽博士學位、日本學士院院士、及德國、英國、Pasteur 研究所等的各種會員資歷，但有細菌屬名以他的名字命名才是無上的榮譽。1944年（昭和19年）授頒文化勲章(Orders of Culture)，1936年被任命「錦鶏間祗侯」(kinkei no ma shikou)(大日本帝国憲法下宮廷中之ㄧ個地位。華族或官吏有功勞者之獎勵。次於「麝香間祗侯」。「錦鶏間」為京都皇宮中學者房間)；其後又受「正三位勲一等瑞宝章=Orders of Sacred Treasure」。著有「一個細菌學者的回想」及其他教材書。

至於為何志賀之末年會如此赤貧，有人以為是他受到國內學派壓制的結果；或是因為空襲時，失去一切；或是兩者都有。

 一位記者專訪時，這位老人和生病的兒子、媳婦、三個孫子住在一破舊的房子；家裡的「障子」[註]全用舊報紙張貼修補、家中暗淡，令人心情沈重。他取出綬頒的各種絢麗獎章，在破損的褟褟米上對照之下，訪者不禁心酸，湧出漠然的不平與寂寞感。這位穿著像一位鄉下老公公的學者、戴著自己修理的眼鏡，謙虛地表示，「為學問、為人類福祉，盡力五十年，雖然貧窮，心中仍是竊竊地感到欣慰」。[註：日本房子用可以稍透光、特製白紙張貼的sliding door-wall]。

 

記者離開時，三個幼小的孫子到屋外一直對他搖手，到他的影子消 失在樹林中。

[土門拳—攝影家1909-1990:『風貌』より。http://homepage1.nifty.com/namakemono/life2/siga.html]