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Infezioni urinarie in Gravidanza

Giuseppe GernoneStruttura Complessa di Nefrologia e Dialisi Putignano

Azienda Sanitaria Bari http://www.asl.bari.it/UnitaOperativa.aspx?Organizzazione=821

Rene e gravidanzaGestione multidisciplinare, recenti

acquisizioni e future strategieTaormina, 15-16 aprile 2011

Infezione delle Vie Urinarie

• E’ la più comune complicanza infettiva della Gravidanza (G.)

Stamm WE: NEJM 1993, 329: 1328-1334

Forme clinicheASINTOMATICHE

• Batteriuria Asintomatica (BA)

SINTOMATICHE

• Cistite Acuta (CA)

• Pielonefrite Acuta (PNA)

Prevalenza in G.Batteriuria Asintomatica (BA): 2-8%

• bacteriuria is more common in diabetic women: 8 – 14 %

•Cistite Acuta (CA): 1-2%

Pielonefrite Acuta (PNA): 1-2%

Rubin RH, et al 1998Nicolle LE, et al. 2005

Fattori di rischio per le infezioni urinarie in Gravidanza

•Infezioni ricorrenti delle vie urinarie o IVU antecedente la prima visita prenatale•Basso livello socioeconomico•Diabete Mellito•Malformazioni urinarie•Alcune nefropatie (nefropatie interstiziali, da reflusso)

•Età anagrafica avanzata•Anemia falciforme•Attività sessuale •Multiparità•Epoca gestazionale (III trimestre)

Linee guida Rene e Gravidanza della Società Italiana di Nefrologia. Giornale Italiano di Nefrologia 17: 24–46, 2000 Smaill FM, Vasquez JC Cochrane Database Syst Rev 2007 Issue 2

• I due più forti predittori di batteriuria alla prima visita prenatale sono stati un’ IVU antecedente la prima visita prenatale o una storia pregravidica di IVU (escluse donne con diabete mellito, anomalie urologiche, HIV).

Pastore LM, et al. Predictors of urinary tract infection at the first prenatal visit. Epidemiology 1999; 10:282

• Per le donne caucasiche, un grado di istruzionesuperiore ed un’ età di 30 anni erano inversamenteassociate ad infezioni del tratto urinario; tra le afro-americane la presenza di emoglobina S quasiraddoppiava la prevalenza della batteriuria.

Pastore LM, et al. Predictors of urinary tract infection at the first prenatal visit. Epidemiology 1999; 10:282

1. Stasi urinaria conseguente alla dilatazione ureterale durante la G.: Cause Ormonali

Idrouretere Fisiologico

della Gravidanza

Idronefrosi Fisiologica della G: cause meccaniche

2. Changes in renal function during pregnancy: pregnancy-induced glycosuria and aminoaciduria

3. Immune system of the pregnant mother: Modified to accomodate a semiallogeneic fetus

Nowicki B Current Infectious Disease Report 2002

In pregnant mothers NO is operating at a maximum or near-maximum capacity, and therefore has limited capacity to increase in response to a spreading virulent infection, and TLR4 is down-regulated. The simultaneous limited/diminished responsiveness of both NO and TLR4 plays a key role in a reduced gestational responsiveness to inflammation/infection.

Nowicki B, et al. Pathogenesis of gestational urinary tract infection. BJOG 2011;118:109–112

presence of a positive urine culture in an asymptomatic person.

Hooton TM. Urinary tract infections and asymptomatic bacteriuria in pregnancy. Up to Date 19.1 1-2011

Asymptomatic Bacteriuria

Asymptomatic Bacteriuria: Epidemiology

• Bacteriuria has been associated with an increased risk of abortion, preterm birth (2 fold increased risk), low birth weight (54 % increased risk), and perinatal mortality.

• The relationship between asymptomatic bacteriuria, low birthweight and preterm delivery is controversial. Pro-inflammatory cytokines secreted in response to bacterial products (for example, endotoxin) may initiate labour. Intrauterine infection is associated with preterm delivery.

KASS EH. Arch Intern Med 1960; 105:194. Naeye RL. N Engl J Med 1979; 300:819. Mittendorf R, et al. Clin Infect Dis 1992; 14:9 27. Millar LK, et al. Infect Dis Clin North Am 1997; 11:13. Patterson TF, et al. Infect Dis Clin North Am 1997; 11:593. Delzell JE Jr, et al. Am Fam Physician 2000; 61:713. Smaill FM, Vasquez JC Cochrane Database Syst Rev 2007 Issue 2

Other studies suggest that microorganisms may produce arachidonic acid, phospholipase A2

and prostaglandins that play an important role in cervical softening and increasing myometrial free calcium content, which stimulates uterine tone and contractions and consequent preterm labour.

Vazquez JC, Abalos E. Treatments for symptomatic urinary tract infections during pregnancy. CochraneDatabase of Systematic Reviews 2011, Issue 1. Art. No.: CD002256.


• If untreated, persists in 60-85% of cases and is complicated with acute pyelonephritis in 15 to 45% of pregnant women.

• additional complications such as gestational IA / PE (5-fold increased risk) .

Mittendorf R et al: J Reprod Med 41; 491: 1996 Linee guida Rene e Gravidanza della Società Italiana di Nefrologia. Giornale Italiano di Nefrologia 17: 24–46, 2000. Nicolle LE, et al. Clin Infect Dis 2005; 40:643. Smaill FM, Vasquez JC Cochrane Database Syst Rev 2007 Issue 2

Isolamento su due campioni consecutivi di urina di un unico microorganismo ≥ 100.000 cfu/mL. Nicolle LE, et al. Clin Infect Dis 2005; 40:643.

La conferma dello stesso risultato in un secondo esame colturale eseguito a distanza di 4-5 gg, aumenta la predittività nei confronti di una infezione sostenuta dall'organismo identificato a più del 95 %;

80% di predittività nel caso di un unico campioneLinee guida Rene e Gravidanza della Società Italiana di Nefrologia. Giornale Italiano di Nefrologia 17: 24–46, 2000

Smaill FM, Vasquez JC Cochrane Database Syst Rev 2007 Issue 2

Batteriuria Asintomatica: diagnosi

Nella pratica clinica, tuttavia, anche un solo campione di urina è considerato sufficiente ed il trattamento è iniziato per colture ≥ 105

ufc/ml senza aspettare una coltura di conferma.



Test rapidi di screening (dipstick, screening enzimatici, es. sedimento etc.) non hanno sensibilità, specificità e valore predittivo paragonabile all’urinocoltura, pertanto non devono essere usati. L’antibiogramma inoltre è utile nel guidare la terapia. Ciò è particolarmente importante in gravidanza, dove le alternative terapeutiche sono ridotte.Millar L, et al. Obstet Gynecol 2000; 95:601. McNair RD, et al. Am J Obstet Gynecol 2000; 182:1076. Shelton SD, et al. Obstet Gynecol 2001; 97:583. Guinto VT, et al. Cochrane Database Syst Rev 2010 Issue 9

Pyuria is common in subjects with asymptomatic bacteriuria (30%–70% of pregnant women). However pyuria is not an indication for antimicrobial treatment. Nicolle LE, et al. Clin Infect Dis 2005; 40:643. Hooton TM, et al. N Engl J Med. 2000;343(14):992.


Batteriologia IVU in G.

• 80% Escherichia Coli

• 20% Altri Gram- (Klebsiella, Enterobacter, Proteus M., Pseudomonas, Citrobacter)

Gram + (Enterococchi, Stafilocco Aureo, Streptococchi gruppo B)

Macejko AM, Schaeffer AJ. Urol Clin North Am 2007; 34: 35-42.


Quando eseguire lo screening

Se negativo, ripeterlo all’inizio del III Trimestre (1-2% delle donne con prima coltura negativa sviluppa una IVU) od in presenza di sintomi urinari

Se positivo, ripeterlo dopo un ciclo di terapia e poi ogni mese anche se si è negativizzato

Cabiddu F, Castellino S, Daidone G, Giannattasio M, Gesualdo L, Imbasciati E, Gregorini G, Manfellotto D, Montanaro D., Stratta P.: Linee-guida Rene e Gravidanza. G. Ital. Nefrol. 2000; 17: 24-46

Screening for asymptomatic bacteriuria should be performed at 12 to 16 weeks gestation (or the first prenatal visit, if that occurs later).

Lin K, Fajardo K, U.S. Preventive Services Task Force. Screening for asymptomatic bacteriuria in adults. Ann Intern Med 2008; 149:W20.

• Negativizza la coltura nel 90% delle pz con IVU

• Riduce l’incidenza di PNA del 60-75%

• Riduce l’incidenza di “low birthweight”

• Riduce il rischio di parto pretermine.

Antibioticoterapia

Linee guida Rene e Gravidanza. Giornale Italiano di Nefrologia 17: 24–46, 2000. Nicolle LE, et al. Clin Infect Dis 2005; 40:643. USPFTF 2004 . www.guideline.gov aug. 2007. Smaill FM, Vasquez JC Cochrane Database Syst Rev 2007 Issue 2. Guinto VT, et al. Cochrane Database Syst Rev 2010 Issue 9.

•Treatment of bacteriuria with antibiotics may also eradicate organisms colonizing the cervix and vagina that are associated with adverse pregnancy outcomes.

http://www.guideline.gov/

Smaill, F. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2001; Issue 2: CD000490 (Modified)

Antibiotici per la terapia della BA in G

Favour treatment Favour no treatment

Smaill, F. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2001; Issue 2 :CD000490 (Modified)


Favour treatment Favour no treatment

Smaill, F. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2001;Issue 2 :CD000490 (Modified)


Favour no treatmentFavour treatment

Il ricorso ai farmaci in G. deve essere limitato all'indispensabile, in particolare durante il primo trimestre.

Molti antibiotici attraversano la placenta e la totale sicurezza non è stata accertata per nessun antibiotico.

Scelta degli antibiotici in G.


• Antibiotics with a good safety profile in pregnant women include the cephalosporins, penicillins, erythromycin (except the estolate), azithromycin, and clindamycin.

• Ceftriaxone (very high protein binding), may be inappropriate the day before parturition because of the possibility of bilirubin displacement and subsequent kernicterus.

• Fosfomycin is considered safe in pregnancy.

Charles J Lockwood, Urania Magriples, The initial prenatal assessment and routine prenatal care. Up to Date 19.1 1-2011. Hooton TM. Urinary tract infections and asymptomatic bacteriuria in pregnancy. Up to Date 19.1 1-2011. Guinto VT, et al. Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy (Review). Cochrane Database Syst Rev 2010 Issue 9. Stein GE. Single-dose treatment of acute cystitis with fosfomycin tromethamine. Ann Pharmacother 1998; 32:215.

• Aminoglycosides are relatively safe, but carry a risk of ototoxicity and nephrotoxicity.

• Doxycycline is avoided during pregnancy because other tetracyclines have been associated with transient suppression of bone growth and with staining of developing teeth, but available data do not show teratogenic effects from doxycycline.

• Fluoroquinolones are generally avoided during pregnancy and lactation because they are toxic to developing cartilage in experimental animal studies. However, neither adverse effects on cartilage nor an increase in congenital malformations from use during human pregnancy has been documented

www.Reprotox.com. (Accessed November 19, 2009). Cooper WO, et al. Paediatr Perinat Epidemiol 2009;

23:18.

• Trimethoprim is generally avoided in the first trimester because it is a folic acid antagonist, has caused variety of birth defects in experimental animals. However, it is not a proven teratogen in humans.

The safest course is to avoid using trimethoprim in the first trimester if another antibiotic that is safe and effective is available.

www.Reprotox.org. (Accessed July 1, 2009). Crider KS, Cleves MA, Reefhuis J, et al. Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study. Arch Pediatr Adolesc Med 2009; 163:978. Hernández-Díaz S, et al. N Engl J Med 2000; 343:1608. Hernández-Díaz S, et al. Am J Epidemiol 2001; 153:961.

• Nitrofurantoin and sulfonamides have been reported statistically significant associations between a variety of birth defects.

• Nitrofurantoin has also been reported to cause hemolytic anemia in the mother and fetus with G-6PD deficiency.

As above, the safest course is to avoid using nitrofurantoin in the first trimester if another antibiotic that is safe and effective is available.

• Sulfonamides should be avoided in the last days before delivery because they can increase the level of unbound bilirubin in the neonate (Sulfonamides compete with bilirubin for albumin binding sites) and theoretically may increase the risk of kernicterous although kernicterus related solely to in utero sulfonamide exposure has never been reported.

For this reason, these drugs are avoided in the third trimester if another antibiotic is available.

Ben David S, et al. Fundam Clin Pharmacol 1995; 9:503. Crider KS, et al. Arch Pediatr Adolesc Med 2009; 163:978. Urbina O. et al. Enferm Infecc Microbiol Clin 2010 28(6):400-403. Hooton TM. Up to Date 19.1 1-2011.

Quale protocollo terapeutico nella terapia della Batteriuria Asintomatica in G.?

1. Singola dose

2. Ciclo breve (4-7gg)

3. Ciclo lungo (10-14 gg)

Vantaggi: migliore complianceminore esposizione per il fetominori effetti collateralicosti più bassi

Svantaggi: più alto tasso di recidive.

Batteriuria Asintomatica: Dose Singola


Quale protocollo terapeutico nella BA in G

Single-dose therapy and shorter courses of three

days were used with success in some studies.Lucas MJ, Cunningham FG. Urinary infection in pregnancy.Clinical Obstetrics and Gynecology 1993;36(4):855–68.

A more recent meta-analysis, demonstrated no

significant difference between single dose and

longer duration regimens in terms to cure

asymptomatic bacteriuria and prevent its

recurrence.Villar J, Lydon-Rochelle MT, et al. Duration of treatment for asymptomatic bacteriuria during pregnancy Cochrane Library, Issue 2, 2003. Oxford: Update Software.


Villar J, Lydon-Rochelle MT, Gülmezoglu AM, Roganti A. Duration of treatment for asymptomatic

bacteriuria during pregnancy (Cochrane Review). In: The Cochrane Library, Issue 2, 2003. Oxford: Update

Software.

Single dose Short course


Villar J, Lydon-Rochelle MT, Gülmezoglu AM, Roganti A. Duration of treatment for asymptomatic

bacteriuria during pregnancy (Cochrane Review). In: The Cochrane Library, Issue 2, 2003. Oxford: Update

Software.

Short courseSingle dose

While short-course therapy of asymptomatic

bacteriuria has become accepted practice, the

optimal duration of treatment is unknown and

standard treatment regimens are currently

recommended.

Smaill FM, Vasquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy (Review) Cochrane Database Syst Rev 2007 Issue 2 Art. No.: CD000490

Sebbene il trattamento breve della batteriuria asintomatica è divenuto una pratica accettata, la durata ottimale del trattamento è sconosciuta, pertanto sono attualmente raccomandati regimi di trattamento standard.

Although there were no significant differences in

symptomatic infections, preterm deliveries and

tolerance of subjects observed between the short and

long dosing schedules, more treatment failures,

however, were seen in the short-dosing (one to three

day) schedule, suggesting the superiority of the

traditional-(seven day)-dosing schedule.

Guinto VT, De Guia B., Festin MR, Dowswell T. Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy (Review). Cochrane Database Syst Rev 2010 Issue 9. Art. No.: CD007855.

Sebbene non vi siano differenze significative nell’incidenza di infezioni sintomatiche, parto pretermine e tolleranza alla terapia tra i trattamenti brevi e quelli di più lunga durata, un maggior numero di insuccessi terapeutici è stato osservato proprio con i cicli brevi (1-3 giorni) il che suggerisce la superiorità del trattamento tradizionale (7 giorni).

Fosfomycin in a single dose versus a 7-day course of amoxicillin-clavulanate for the treatment of asymptomatic bacteriuria during pregnancy.Estebanez A, Pascual R, Gil V. Ortiz F, Santibáñez M, Pérez Barba C.Eur J Clin Microbiol Infect Dis. 2009 Dec; 28(12):1457-64

A randomised, prospective, interventional, analytical, longitudinal study. One hundred and nine patients were randomly assigned to two groups: 56 were treated with amoxicillin-clavulanate and 53 with fosfomycin.

•The efficacy of the two regimens was similar and the eradication rate was over 80% in both groups (P = 0.720) (relative risk [RR] 1.195, 95% confidence interval [CI]: 0.451-3.165). •The number of reinfections was greater in the amoxicillin-clavulanate group (P = 0.045). •The secondary effects were lower in the fosfomycin group (P = 0.008). •There were no significant differences in the number of persistences (P = 0.39), development of symptomatic urinary infections (P = 0.319) or recurrences (P = 0.96). Treatment with a single dose of fosfomycin is as effective as the standard course of treatment with amoxicillin-clavulanate and may be preferable due to its simpler administration and the smaller number of reinfections.

If bacteriuria persists after two or more courses of therapy continuous suppressive therapy is considered for the duration of pregnancy.

Guinto VT, et al. Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2010 Issue 9

If the follow-up culture is positive, another course of antimicrobial should be given either the same antimicrobial in a longer course or a different antimicrobial.

Hooton TM. Urinary tract infections and asymptomatic bacteriuria in pregnancy. Up to Date 19.1 1-2011.

Follow-up

Schema soppressivo per tutta la durata della gravidanza:

quotidiano: basse dosi serali di antibiotico fino a 4-6 mesi post-partum (es. cefalexina 250 -500 mg, nitrofurantoina 50-100 mg)

ovvero

intermittente: assumendo la stessa posologia del farmaco subito dopo ogni rapporto sessuale

IVU ricorrenti o persistenti Protocolli terapeutici

Cabiddu F, Castellino S, Daidone G, Giannattasio M, Gesualdo L, Imbasciati E, Gregorini G, Manfellotto D, Montanaro D., Stratta P.: Linee-guida Rene e Gravidanza. G. Ital. Nefrol. 2000; 17: 24-46Hooton TM. Urinary tract infections and asymptomatic bacteriuria in pregnancy. Up to Date 19.1 1-2011.

Cistite acuta in G.

Prevalenza 1-2%

Sintomi specifici: disuria, dolore sovrapubico, talora macroematuria

non specifici: frequenza e urgenza minzionale

Hooton TM. Acute cystitis in women. Up to Date 19.1 1-2011.

Vazquez JC, Abalos E. Treatments for symptomatic urinary tract infections during pregnancy. CochraneDatabase of Systematic Reviews 2011, Issue 1. Art. No.: CD002256.

• No correlation has been established between acute cystitis and increased risk of low birth weight, preterm delivery or pyelonephritis, perhaps because pregnant women with symptomatic UTI usually receive treatment.

Millar LK, Cox SM. Urinary tract infections complicating pregnancy. Infect Dis Clin North Am 1997; 11:13.

Acute cystitis Epidemiology

In pazienti sintomatiche anche una concentrazione inferiore a 105 ufc/ml può essere indicativa di una infezione.

Kass, EH. Pyelonephritis and bacteriuria: A major problem in preventive medicine. Ann Intern Med 1962; 56:46.

Diagnosi

Avviare empiricamente il trattamento delle forme sintomatiche anche prima del risultato dell’urinocoltura, in base alle prevalenze batteriologiche note

Indagare già in G. con l’ecografia le IVU ricorrenti, concludendo le indagini dopo il parto

Trattamento: raccomandazioni


Acute Cystitis Treatment

Pregnant women with acute cystitis should be

treated with a three to seven day course of

antibiotics as long as they do not have symptoms

suggestive of pyelonephritis (eg, flank pain,

nausea/vomiting, fever [>38ºC], and/or

costovertebral angle tenderness).


• All of the antibiotics studied were very effective during pregnancy in terms of cure rates, recurrent infection, incidence of preterm delivery, and the need for a change of antibiotics.

• Complications were very rare.

• There was not enough evidence to recommend a particular treatment scheme.

Vazquez JC, Abalos E. Treatments for symptomatic urinary tract infections during pregnancy. CochraneDatabase of Systematic Reviews 2011, Issue 1. Art. No.: CD002256.…intravenous and oral cephradine versus intravenous and oral

cefuroxime (Santiago 2000);intramuscular cephazolin versus intravenous ampicillin plus

gentamicin (Los Angeles 1998);intramuscular ceftriaxone versus intravenous ampicillin plus

gentamicin (Los Angeles 1998);intramuscular ceftriaxone versus intravenous cephazolin (Los

Angeles 1998);oral ampicillin versus oral nitrofurantoin (Mexico 1989);oral fosfomycin trometamol versus oral ceftibuten

(Bratislava 2001) …

Empiric Treatment Regimens

Pending urine culture and sensitivity testing:

• Nitrofurantoin (100 mg orally every 12 hours for five to seven days)

• Cefpodoxime (100 mg twice daily for three to seven days)

• Amoxicillin-clavulanate (500 mg orally every 12 hours for three to seven days)

• Fosfomycin (3 g orally as a single dose)

Other regimens include TMP-SMX [DS] (twice daily for three days) in the second trimester (avoid in first trimester or near term).


Schema soppressivo (chemioprofilassi) per tutta la durata della gravidanza (pz. diabetiche già dal primo episodio):quotidiano: basse dosi serali di antibibiotico fino a 4-6 mesi

post-partum (es. cefalexina 250 -500 mg, nitrofurantoina 50-100 mg)

ovvero

intermittente: assumendo la stessa posologia del farmaco subito dopo ogni rapporto sessuale (IVU antecedenti)

IVU ricorrenti o persistenti Protocolli terapeutici



Acute Pyelonephritis

• Is suggested by flank pain, abdominal or pelvic pain, nausea/vomiting, fever (>38ºC), and/or costovertebral angle tenderness and may occur in the presence or absence of cystitis symptoms.

• Rarely, patients with acute pyelonephritis present with sepsis, multiple organ system dysfunction, shock, and/or acute renal failure.Hooton TM. Clinical manifestations; diagnosis; and treatment of acute pyelonephritis Up to Date 19.1 1-2011

Prevalenza: 1-2%; seconda metà G.; unilaterale dx.Cabiddu F, Castellino S, Daidone G, Giannattasio M, Gesualdo L, Imbasciati E, Gregorini G, Manfellotto D, Montanaro D., Stratta P.: Linee-guida Rene e Gravidanza. G. Ital. Nefrol. 2000; 17: 24-46. Hill JB, et al Acute pyelonephritis in pregnancy. Obstet Gynecol 2005; 105:18. Archabald KL, et al. Impact of trimester on morbidity of acute pyelonephritis in pregnancy. Am J Obstet Gynecol 2009; 201:406.e1.

Complications and pregnancy outcomes

• Complications included anemia (23 %), bacteremia (17 %) with septic shock (1-2 %), respiratory insufficiency (7 %) up to ARDS (2%), and renal dysfunction (2 %) with Acute renal failure associated with microabscesses in isolated cases.

Cabiddu F, Castellino S, Daidone G, Giannattasio M, Gesualdo L, Imbasciati E, Gregorini G, Manfellotto D, Montanaro D., Stratta P.: Linee-guida Rene e Gravidanza. G. Ital. Nefrol. 2000; 17: 24-46. Hill JB, et al Acute pyelonephritis in pregnancy. Obstet Gynecol 2005; 105:18.

• Preterm birth occurred in only 5 percent of women with acute pyelonephritis which is similar to the rate in the general obstetric population.

PNA: Trattamento

Ospedalizzazione Antibioticoterapia ev

Antibioticoterapia per os dopo 48h di defervescenza

Terapia profilattica continua sino a 2 sett. post-partum

Sorveglianza continuaovvero



**

* Carbapenems are usually effective in the treatment of ESBL infections

Treatment

• Patients should have definite improvement within 24 to

48 hours. Once afebrile for 48 hours, patients can be

switched to oral therapy (guided by culture susceptibility

results) and discharged to complete 10 to 14 days of

treatment.

• If symptoms and fever persist beyond the first 24 to 48

hours of treatment, a repeat urine culture and urinary

tract imaging studies should be performed to rule out

persistent infection and urinary tract pathology.

American College of Obstetricians and Gynecologists. Antimicrobial therapy for obstetric patients. ACOG educational bulletin 245. 1998; Washington, DC.

• Le pazienti devono mostrare un deciso miglioramento entro 24-48 ore. Una volta apirettiche per 48 ore, le pazienti possono essere trattate con terapia orale (guidata dai risultati dell’antibiogramma) quindi dimesse con l’indicazione al trattamento per 10 - 14 giorni.

• Se i sintomi e la febbre persistono oltre le prime 24-48 ore di trattamento, è necessario ripetere l’urinocoltura ed effettuare uno studio delle vie urinarie per escludere foci d’infezione persistente e patologie del tratto urinario.

Acute Pyelonephritis: Follow-up

• Recurrent pyelonephritis occurs in 6 to 8 % of

women.

• As a result, low dose antimicrobial prophylaxis

- nitrofurantoin (50 to 100 mg orally at bedtime)

- cephalexin (250 to 500 mg orally at bedtime)

and periodic urinary surveillance are

recommended for the remainder of the

pregnancy.Lenke RR, VanDorsten JP, Schifrin BS. Pyelonephritis in pregnancy: a prospective randomized trial to prevent recurrent disease evaluating suppressive therapy with nitrofurantoin and close surveillance. Am J Obstet Gynecol 1983; 146:953. American College of Obstetricians and Gynecologists. Antimicrobial therapy for obstetric patients. ACOG educational bulletin 245. 1998; Washington, DC. Cabiddu F, Castellino S, Daidone G, Giannattasio M, Gesualdo L, Imbasciati E, Gregorini G, Manfellotto D, Montanaro D., Stratta P.: Linee-guida Rene e Gravidanza. G. Ital. Nefrol. 2000; 17: 24-46

Conclusioni Trattare le batteriurie asintomatiche con

l’obiettivo di eradicarle per tutta la durata della gravidanza (A)

Avviare empiricamente il trattamento delle forme sintomatiche anche prima del risultato dell’urinocoltura, in base alle prevalenze batteriologiche note (C)

Ospedalizzazione per il trattamento della PNA Accortezza in scelta dell’antibiotico e durata

del trattamento.

Il mirtillo contiene acido malico, acido citrico, glucosio, fruttosio e acido quinico.

Quest’ultimo causa l’escrezione di elevate quantità di acido ippurico che

agisce come agente anitibatterico

Succo di mirtillo nelle IVU

Kenney, 1979

• Cranberries have a complex phytochemical profile,

which includes 3 classes of flavonoids (flavonols,

anthocyanins and proanthocyanidins), catechins,

hydroxycinnamic and other phenolic acids, and

triterpenoids.

• Inhibition of adherence of E. coli to uroepithelial

cells, this may help prevent bladder and other

urinary tract infections.

Neto CC: Cranberry and its phytochemicals: a review of in vitro anticancer studies. J Nutr, suppl., 2007; 137: 186S. Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database of Systematic Reviews. 2008. Issue 1. art. No.: CD 001321.

Succo di mirtillo nelle IVU

Jepson RG, Craig JC. Cranberries for preventing urinarytract infections. Cochrane Database of SystematicReviews. 2008. Issue 1. art. No.: CD 001321.

• There is some evidence that cranberry juice maydecrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs.

• Cranberry juice may not be acceptable over long period of time.

• It is not clear what is the optimum dosage or method of administration (e.g. juice, tablets or capsules).

J Urol. 2008 Oct;180(4):1367-72.

Daily cranberry juice for the prevention of asymptomatic bacteriuria in

pregnancy: a randomized, controlled pilot study.

Wing DA, Rumney PJ, Preslicka CW, Chung JH.

Department of Obstetrics and Gynecology, University of California, Irvine,

Orange, California 92868, USA.

A total of 188 women were randomized to cranberry or placebo in 3 treatment arms A-cranberry 3 times daily (58), B-cranberry at breakfast then placebo at lunch and dinner (67), C-placebo 3 times daily (63). After 27.7% (52 of 188) of the subjects were enrolled in the study the dosing regimens were changed to twice daily dosing to improve compliance.

RESULTS: 27 urinary tract infections in 18 subjects in this cohort, with 6 in 4 group A, 10 in 7 group B and 11 in 7 group C (p = 0.71). There was a 57% and 41% reduction in the frequency of asymptomatic bacteriuria and all urinary tract infections, respectively, in the multiple daily dosing group. Of 188 subjects 73 (38.8%) withdrew, most for gastrointestinal upset.

CONCLUSIONS: These data suggest there may be a protective effect of cranberry ingestion against asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. Further studies are planned to evaluate this effect.

Plamen H. Yovchevski, Emma E. Keuleyan and Nencho P. Smilov

Departments of Nephrology and Urology and Clinical Microbiology Laboratory Medical

Institute of the Ministry of the Interior Sofia, Bulgaria

Re: Daily Cranberry Juice for the Prevention of Asymptomatic

Bacteriuria in Pregnancy: A Randomized, Controlled Pilot Study

J Urol. 2009 Mar;181(3):1503-4; author reply 1504.

We recommend any of the following regimens (if the organism is susceptible):

•Nitrofurantoin (100 mg orally every 12 hours for five to seven days)

•Amoxicillin (500 mg orally every 12 hours for three to seven days)

•Amoxicillin-clavulanate (500 mg orally every 12 hours for three to seven days)

•Cephalexin (500 mg orally every 12 hours for three to seven days)

•Fosfomycin (3 g orally as a single dose)


Nitrofurantoin and fosfomycin are active in vitro against many infections caused by ESBL-producing strains

Rodríguez-Baño J, et al. Community infections caused by extended-spectrum beta-lactamase-producing E. coli. Arch Intern Med 2008; 168:1897.


• Multiparous women

• Similar prevalence as seen in nonpregnant women

• The organisms are also similar in pregnant and nonpregnant women

• Bacteriuria often develops in the first month of pregnancy

Nicolle LE, et al. Clin Infect Dis 2005; 40:643.

Macejko AM, Schaeffer AJ. Urol Clin North Am 2007; 34: 35-42.

Guinto VT, et al. Cochrane Database Syst Rev 2010 Issue 9


Posologia: considerare modifiche della farmacocinetica in G. che condizionano livelli ematici ridotti e richiedono aumento posologico soprattutto in presenza di infezioni severe:

- aumento del volume di distribuzione- aumentata eliminazione renale- accelerazione metabolismo epatico per attivazione degli enzimi microsomiali epatici indotta dal progesterone.

Allattamento: la maggior parte degli antibiotici si ritrova nel latte, per cui non è raccomandabile l’allattamento nelle donne in terapia.

Scelta degli antibiotici in G. (II)


CURRENT CONCEPTS IN THE PATHOGENESIS OF NONGESTATIONAL UTI

“RECEPTOR MEDIATED ASCENDING INFECTION”

Nowicki B Current Infectious Disease Report 2002

infezioni urinarie in gravidanza - nephromeet · infezioni urinarie in gravidanza giuseppe gernone...

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