Resuscitation Council (UK) Adult Advanced Life Support Introduction This section on adult advanced life support (ALS) adheres to the same general principles as in Guidelines 2000, but incorporates some important changes. The guidelines in this section apply to healthcare professionals trained in ALS techniques. Laypeople, first responders, and automated external defibrillator (AED) users are referred to the basic life support (BLS) and AED sections. Guideline changes
a fact sheet from react – action on antibiotic resistance, www.reactgroup.org First edition May 2008 Burden of Antibiotic Resistance
on Women's Health
u Sepsis is still one of the major cau-
adequate treatment of the mother
Newborn babies may become blind.
ses of death following abortion and
and her child cannot be guaranteed.
childbirth. Resistance is common
u An estimated 3 million treatment
among several of the bacterial spe-
u Improvement of maternal health
failures due to resistant gonorrhoea
cies causing infections, but in spite of
as stated in millennium Develop-
occur each year in the world and will
the serious consequences, the size as
ment Goal (mDG) 5 will be difficult
incur an additional cost of US$ 500
well as the burden of such resistance
to achieve for such reasons.
million. When treatment guidelines
is to a large extent unknown.
recently had to be changed in the
u Antibiotic resistance may also be a
US, due to increasing resistance to
u Infections during pregnancy may
serious problem when women cont-
ciprofloxacin, the cost of treatment
also lead to pre-term delivery, still-
ract sexually transmitted infections
increased fivefold. the risk of HIV-
birth and death of the infant in sep-
(StI), especially gonorrhoea. Unt-
transmission increases considerably
sis. As long as the prevalence of anti-
reated or untreatable infections may
if StI are impossible to treat adequa-
biotic resistance is almost unknown,
lead to pelvic inflammatory disease,
and the urgent need of new effective
causing chronic pain and discomfort,
antibiotics is not being provided for,
infertility, and ectopic pregnancies.
Scope of tHe pRoBlem
Infections in the female genital tract – RTI (reproductive tract infections) – include endogenous infections as well as iatrogenic and sexually trans-mitted infections (STI).1 Infections during pregnancy and after childbirth may follow any of these. Resistance to antibiotics commonly used for treating such infections has emerged in many parts of the world.2 However, data is lacking or very scarce regarding the burden of antibiotic resistance within the field of women´s health, although the consequences can be severe.
Infections following abortions,
pregnancy and childbirth
With the institution of antiseptic prac-
tices and later the availability of antibi-
otics, the incidence of puerperal sepsis
decreased considerably, but it is still,
along with haemorrhage, one of the
main causes of maternal deaths world- about 13% of all pregnancy related case per 100,000. Three hundred and deaths in the world.10,11,12 Deaths due forty nine cases of congenital syphilis Infections include metritis, pelvic to abortion are most common in the were reported there in 2006.17 cellulitis and abscess, peritonitis fol- Caribbean and Latin America. The spe- lowing uterine perforation, and septi- cific cause of death is often unknown but is considered to be haemorrhage or sepsis in most cases. In a study in StI and other infections of the
Malawi, 77.1% of the deaths after Infections are often caused by several abortions were due to sepsis.4 species of bacteria. E coli, beta haemo- Untreated infections increase the prob- There is so far no knowledge about lytic streptococci, S aureus and anaer- ability of acquisition and transmission the impact of antibiotic resistance obes are all common pathogens.6, 15, 19, 20 when fatal infections occur.
Other agents include Klebsiella spp, An estimated 340 million cases of enterococci, and N. gonorrhoeae. C. curable STI occur annually in adults. puerperal sepsis and infections
trachomatis and Mycoplasma spe- Most are in south and south-east Asia cies may also be responsible, as may and sub-Saharan Africa. Infections More than 500,000 women die each (rarely) Clostridia.6 may lead to acute and chronic symp- year due to complications during toms and long term consequences.
pregnancy and childbirth.3, 13 Sepsis is As many as 70% of infections in estimated to be the cause of maternal Effective and early treatment of STI women may be asymptomatic.9 Infec- deaths in 0.5-15% of cases. It is signifi- is essential to decrease the transmis- tions during pregnancy can have cantly more common in Africa, Asia, sion of the actual disease, and of HIV. adverse effects and may cause infec- Latin America and the Caribbean The choice of antibiotic for treatment tions in the newborn baby.
than in developed countries.3 Infec- depends on knowledge of local resist- Syphilis during pregnancy may tion occurs even more often after Cae- ance patterns. As an example, since result in stillbirth, neonatal death or sarean section.14,15 On rare occasions 2007 ciprofloxacin is no longer rec- congenital syphilis. amniocentesis may also lead to serious ommended by the CDC as the first-line STI caused by Clamydia trachoma treatment for gonorrhoea in the US tis and N. gonorrhoeae: due to high level of resistance.28, 32 The If not treated adequately, complica- same decision had to be made in India.34 tions may lead to pelvic inflammatory An estimated 62 million cases of gon- Penicillins have remained effective for disease (PID), infertility, chronic pain orrhoea occur each year in the world.9 the treatment of early syphilis.31 and ectopic pregnancies.9 40-50% of In the US, reported rates of gonor- Resistance among aerobic Gram- ectopic pregnancies can be attributed rhoea and C. trachomatis infections negative bacteria like E. coli is common to earlier PID. Transmission of infec- among women were respectively 124.3 and several strains are also resistant to tion to the infant during birth may lead and 515.8 per 100,000 in 2006.17 third-generation cephalosporins (see to blindness and in the case of C. tra Infection may be 10-100 times more factsheet on MRGN). E. coli carried as chomatis also to pneumonia.
common in low-income communities part of the normal flora can be resist- according to the WHO.
ant, and maternal colonisation with resistant bacteria may lead to neonatal sepsis.21 Prophylactic treatment given More than 1 million infants are born against Group B streptococci may lead Sepsis following abortion
with congenital syphilis each year in to neonatal infections with resistant An estimated 19-20 million unsafe ter- bacteria, e.g. E coli.22-24 minations take place each year in the In the US, syphilis in women is The number of community- and hos- world, and around 68,000 women die much more uncommon than in men pital-associated methicillin resistant S. as a consequence, which accounts for and increased by 11.1% in 2006 to one aureus (MRSA) infections is increasing in the post-partum period.20,25,26 Two out of 305 women screened had vaginal colonisation with MRSA.
Penicillinase-producing N. gonorr hoeae (PPNG) emerged in 1976. Surveillance programmes in several countries,27, 28, 29 and the global gono- u react links a wide range of individuals, u react believes that anti biotics should coccal antimicrobial surveillance pro- organisations and networks around the be used appropriately, their use reduced gramme (GASP) of the WHO monitor world taking concerted action to when of no benefit and their correct and development of resistance among N. respond to antibiotic resistance.
specific use increased when needed.
gonorrhoeae. In the US, 19.6% of N. u our vision is that current and future u react believes that awareness of ecolo- gonorrhoeae were resistant to penicil- generations of people around the globe gical balance is needed as part of an inte- lin, tetracycline or both in 2005, an should have access to effective treatment gral concept of health.
increase from 15.9% in 2004.5 In the of bacterial infections.
UK, 17.9% of isolates were penicillin-resistant in 2005 but the figure fell to 9.5% in 2006. Tetracycline resistance The risk of HIV-transmission increases was present in 36.9% of isolates, again considerably if STI are imposible to treat a decrease from 48%.27 In India, peni- cillin resistance increased significantly to 68.4% in 2003 but decreased to 18.2% in 2006. In other parts of Asia, 9-90% of isolates are penicillin-resist- failures globally each year due to anti- ant, as are over 35% in sub-Saharan n Increased mortality and morbid- biotic resistance in gonorrhoea has ity, e.g. chronic pelvic inflamma- been made. This would incur an extra Resistance to fluoroquinolones is tory disease (PID) with infertility, cost of US$ 500 millions each year.35 increasingly prevalent globally. The chronic pain, ectopic pregnancy The cost of treatment of resistant go prevalence in Hongkong and other with severe consequences33 norrhoea is five times higher when parts of China is 99%.1 In India resist- n High cost of second-line treatment ciprofloxacin has had to be replaced ance to ciprofloxacine increased to and hospital care by ceftriaxone. The cost of treatment 97.2% in 2006.34 n Psychological effects of MRSA infections is probably three Overall quinolone resistance among times higher than that incurred by sus- N. gonorrhoeae has increased steadily ceptible strains.
to around 13% in the US in 200628 and to 21.7% in the UK in 2005.27 n Increased cost of diagnostic proce- Dearth of resources
Confirmed resistance to ceftriaxone n Lack of access to skilled antenatal has still not been recorded worldwide n High costs of alternative drugs, which but isolates with intermediate suscep- may have to be administered i.m. n Lack of safe conditions during tibility have been identified.28 n Availability of drugs In India, 5,5% of isolates were less n Need for higher level of care, pos- n Lack of access to effective contra- susceptible in 2006.34 Resistance to sibility of emergency operations (in ceptives and safe abortions cefixime has not yet been identified. the case of ectopic pregnancies), n Lack of adherence to STI manage- Isolates with higher azithromycin increased workload for healthcare MIC were also found to have increased n Lack of quality-assured culture and over the years, and 5% of the isolates antimicrobial susceptibility testing were resistant to azithromycin in Europe in 2004.29 In the Caribbean n Maternal death with far-reaching n Lack of adequate and affordable and South America, these figures vary consequences for the whole family, drugs for treatment from 16% to 70%.2 long-term illness and lack of pro- n Lack of knowledge about overuse Resistance to spectinomycin varies or misuse of medicines from 0% to about 5%.2 n Stillbirths or deaths of newborn Antibiotic resistance among C. babies; need for care of sick new- Urgent needs
trachomatis is still low, but in vitro n Train caregivers in appropriate resistance to macrolide antibiotics has n Need for care of orphans infection control and rational drug been detected.30 Since 2002 treatment n Need for care of disabled children failures have occurred in the US when n Increased transmission of HIV n Improve diagnostic capacity and early syphilis has been treated with documentation of infection, aetio- azithromycin. A high prevalence of the logical agents and their antimicro- resistant bacteria has also been found bial susceptibilities. coNSeQUeNceS of
n Develop hospital-based and com- munity-based surveillance systems to monitor antibiotic resistance QUAlItAtIVe coNSeQUeNceS
Quantification of morbidity, mortality trends, antibiotic use and treatment or costs due to antimicrobial resistance associated with infections during preg- n Perform clinical trials to identify the Infections due to resistant bacteria can nancy or delivery is impossible for the most effective drugs/combinations be severe and may require readmis- time being because of lack of reliable for specific indications.
sion, intensive and prolonged care, data. Difficulties include inadequate n Develop locally relevant guidelines, and facilities for culture and suscep- diagnostics, uncertain aetiology of taking into account local suscepti- tibility testing. Mortality increases if infections, other coexisting conditions bility patterns, availability and cost initial therapy is inappropriate. Excess (haemorrhage, ecclampsia etc) and of drugs, diagnostic facilities etc.
cost of therapy is high. sometimes lack of proper records.
n Develop new medicines which can Based on figures from the USA, cure STI and other infections suf- an assumption of 3 million treatment fered by women.
1. Global Strategy for the prevention 13. Hill K et al. Estimates of maternal 25. Saiman L et al. Hospital transmis- and control of sexually transmitted mortality worldwide between 1990 sion of communicquired methicil- infections; 2006-2015 WHO 2007 and 2005: an assessment of available lin-resistant Staphylococcus aureus 2. Okeke IN et al. Antimicrobial resist- data. Lancet 2007; 370: 1311-19 among postpartum women. Clin ance in developing countries. Part 14. Liu S et al. Maternal mortality and Infect Dis, 2003. 37(10): 1313-9.
I: recent trends and current status. severe morbidity associated with 26. Rotas M et al. Methicillin-resistant Lancet Infect Dis, 2005. 5(8): 481- low-risk planned cesarean delivery Staphylococcus aureus necrotizing versus planned vaginal delivery at pneumonia arising from an infected 3. Khan KS, Wojdyla D, Say L, Gulm- term. Cmaj, 2007. 176(4): 455-60.
episiotomy site. Obstet Gynecol, ezoglu AM and Van Look PF. WHO 15. Kankuri E et al. Incidence, treatment 2007. 109(2 Pt2): 533-6.
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27. GRASP. The Gonococcal Resistance a systematic review. Lancet, 2006. Acta Obstet Gynecol Scand, 2003. to Antimicrobials Surveillance pro- 367(9516): 1066-74.
gramme, year 2006 report. London 4. Lema VM, Changole J, Kanyighe 16. Elchalal U et al. Maternal mortality Health Protection agency, 2007.
C and Malunga EV. Maternal mor- following diagnostic 2nd-trimester 28. CDC´s Sexually Transmitted Dis- tality at the Queen Elizabeth Cen- amniocentesis. Fetal Diagn Ther, eases Treatment Guidelines, 2006; tral Teaching Hospital, Blantyre, 2004. 19(2): 195-8.
Fluoroquinolones No longer Rec- Malawi.East Afr Med J, 2005. 17. www.cdc.gov/std/stats.htm March ommended for Treatment of Gono- coccal Infections. MMWR 2007; 5. Sharma M, Uprety D, Pokhrel M, 18. Va´squez-Manzanilla O et al. Con- Karki A, Sharma U and Babu S. genital syphilis in Valera, Venezuela, 29. Martin IM, Hoffmann S, Ison Ca. Maternal mortality at BP Koirala Journal of Tropical Pediatrics 2007; European Surveillance of Sexually Institute of Health Sciences, Nepal: Transmitted Infections (ESSTI): review of 6 years. Trop Doct, 2005. the first combined antimicrobial 35(1): 25-6.
19. Bilal NE, Gedebou M, and Al- susceptibility data for Neisseria Ghamdi S, Endemic nosocomial 6. Cunningham FG et al. Williams gonorrhoeae in Western Europe. J. infections and misuse of antibiotics Obstetrics, 22nd Edition. 2005: Antimicrob Chemother 2006; 58: in a maternity hospital in Saudi Ara- McGraw-Hill Companies, Inc.
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drottninggatan 4, 3 tr fax: +46 18 471 6609
Uppsala University se - 751 05 Uppsalasweden
Eur J Vasc Endovasc Surg 22, 389–395 (2001)doi:10.1053/ejvs.2001.1492, available online at http://www.idealibrary.com on Apoptosis in Vascular Disease T. C. F. Sykes∗1,2, A. G. Morris1, A. W. Bradbury2 and D. Mosquera2 1Biological Sciences, University of Warwick, Coventry CV4 7AL, 2Department of Vascular Surgery,