Le infezioni dei presidi elettronici intracardiaci
Gianfranco Dedivitiis
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CIED: casistica, complicanze e mortalità.
Fattori di rischio.
Classificazione delle infezioni CIED.
Microbiologia delle infezioni CIED.
Clinica.
Diagnosi.
Terapia.
Questioni aperte.
Approximately 67,000 AICDs and 178,000 PMs were implanted in
2004 in the United States, increasing 60% and 19%, respectively,
since 1997.
Cardiac Device Implantation in the United States from 1997 through 2004: A Population-based Analysis
A.Chunliu Zhan, MD; J Gen Intern Med. 2007;23(suppl 1)13-196
About 70% of the patients
were aged 65 years or
older and more than 75%
of the patients had 1 or
more comorbid diseases.
Cardiac Device Implantation in the United States from1997
through 2004: A Population-based Analysis
AChunliu Zhan, MD; J Gen Intern Med. 2007;23(suppl 1)13-19
Selected outcome estimates for AICD patients for the years 1997 to 2003
(tables for other comes and other patient groups available upon request).
Mean LOS decreased continuously, whereas charges nearly doubled.
In-hospital mortality rates decreased and complication rates fluctuated
slightly during the period.
Overall, adverse outcomes were associated with advanced age,
comorbid conditions and emergency admissions, and there was no
consistent volume–outcome relationship across different outcome
measures and patient groups.
Cardiac Device Implantation in the United States from 1997 through 2004: A Population-based Analysis
AChunliu Zhan, MD; J Gen Intern Med. 2007;23(suppl 1)13-19
Between 1975 and 2004, 1291 adult patients underwent PPM implantation.
The incidence of PPM placement by 5-year interval: adjusted incidence
increased from 36.6 per 100 000 person-years in 1975 to 1979 to 99.0 per
100 000 person-years in 2000 to 2004.
Temporal trends in permanent pacemakerimplantation: A population-based study
Daniel Z. Uslan, MD,a Imad M. Tleyjeh, MD,b Larry M. Baddour, MD, Am Heart J. 2008;155:896-903
The mean age at PPM implantation was 76 ± 12.6 years, and 52% were female.
Permanent pacemaker implantation increased across all age groups.
Permanent
pacemaker
implant
incidence
increased from 7.06,
140.7, 306.2, and 422.0
per 100 000 personyears in 1975 to 1979
for age quartiles 18 to
69, 70 to 79, 80 to 84
and
85
to
110,
respectively
to
21.5,
364.1,
901.6,
and
1026.8 per 100 000
person-years in 2000 to
2004 (P b.0001 for all
trends).
Temporal trends in permanent pacemakerimplantation: A population-based study
Daniel Z. Uslan, MD,a Imad M. Tleyjeh, MD,b Larry M. Baddour, MD, Am Heart J. 2008;155:896-903
Between 1975 and 2004, dual-chamber pacing has became used
much more frequently than single-chamber pacing.
Between 1993 and 2008, over 4.2 million primary implantations of
PM (3,204,700 records) and ICD (1,124,000 records)
16-Year Trends in the Infection Burden for Pacemakers and ImplantableCardioverter-Defibrillators in the United States
1993 to 2008
Arnold J. Greenspon, MD,* Jasmine D. Patel,
The importance of the rice in ICD implantations is highlighted by the
increase in 2008 to 35% off all CIED implants.
16-Year Trends in the Infection Burden for Pacemakers and ImplantableCardioverter-Defibrillators in the United States
1993 to 2008
Arnold J. Greenspon, MD,* Jasmine D. Patel,
Italia
Distribuzione degli impianti registrati dal 1981 al 2011
A Proclemer, et al: Registro Italiano Pacemaker e Defibrillatori - Bollettino Periodico 2011
Complication Rates Associated With Pacemaker or Implantable Cardioverter-Defibrillator Generator Replacements and
Upgrade Procedures. Results From the REPLACE Registry
Jeanne E. Poole, MD; Marye J. Gleva, MD;
CIED infections were more commonly observed in elderly patients
The annual rate cardiac implantable electrophysiological device
(CIED) infection remained fairly constant until 2004 when there was a
marked increase. The infection rate increased from 1,53% in 2004 to
2,41% in 2008.
16-Year Trends in the Infection Burden for Pacemakers and Implantable Cardioverter-Defibrillators in the United States
1993 to 2008
Arnold J. Greenspon, MD,* Jasmine D. Patel,
The increased infection burden was associated with increased
financial cost and higher impatient mortality, in hospital
charges increased to over $146.000, which represents an
increase of 47% decade
Increased Long-Term Mortality in Patients with Cardiovascular Implantable Electronic Device Infections
MUHAMMAD RIZWAN SOHAIL, M.D.,* PACE 2014;00:1-9
CIED infection and mortality
• Patients with CIED infection had approximately twice the
mortality at the end of year 1 compared to patients without
device infection.
• Patients with CIED infection, compared to device recipients
without infection, had increased mortality that persisted
for at least 3 years after the admission quarter for all
device types: pacemakers (PMs: 53.8% vs 33%; P < 0.001),
implantable cardioverter defibrillator (ICD: 47.7% vs 31.6%; P
< 0.001), and cardiac resynchronization therapy-defibrillator
(CRT-D: 50.8% vs 36.5%; P < 0.001).
• CIED recipients who develop device infection have increased,
device-dependent, longterm mortality
even after
successful treatment of infection and after discharge
from the hospital.
• The etiology of this durable increase in mortality following CIED
infection is unclear as the cause of death could not be
accurately determined from the administrative database used
in our study. These insights are useful for both clinicians and
patients for making informed decision regarding risks and
benefits of ongoing device therapy after an infectious episode
that requires removal of infected device. Future research
should attempt to identify why patients with CIED infections
have increased long-term risk of death, and evaluate strategies
to minimize this risk.
Patients were divided into group A (bacteremia or device endocarditis) and
group B (localized pocket infection). In-hospital mortality was 29% in
group A and 5% in group B (p 0.02) and was due mostly to sepsis.
Effect of Early Diagnosis and Treatment With Percutaneous Lead Extraction on Survival in Patients With Cardiac Device
Infections
Federico Viganego, MDa, Susan O’Donoghue, MDa, Am J Cardiol 2012;109:1466-1471
RISK FACTORS FOR DEVICE INFECTION
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Risk factors related to infections of implanted pacemakers and
cardioverter-defibrillators: results of a large prospective study.
Circulation. 2007;116:1349 –1355. Klug D, Balde M, Pavin D et al.
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Device-Related Infection Among PatientsWith Pacemakers
Implantable
Defibrillators:
Incidence,
Risk
Factors
Consequences
Pablo B. Nery, M.D.,∗ Russell Fernandes, B.Sc.
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Infections involving cardiac implantable electronic devices.
Hospital Chronicles 2014,vol 9,suppl 1:103-106
Eleni Belesiotou et Al
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Rates of and Factors Associated With Infection in 200 909 Medicare
Implantable Cardioverter-Defibrillator Implants Results From the
National Cardiovascular Data Registry
Jordan M. Prutkin, MD, MHS; Matthew R. Reynolds, MD, Circulation.
2014;130:1037-1043
and
and
PERIOPERATIVE FACTORS
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Use temporary pacing leads before placement of the device ;
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lack of antibiotic prophylaxis before implantation;
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longer operative time;
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operative inesperience ;
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development of postoperative pocket hematoma;
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adverse event during implant requiring reintervention ;
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previous valvular surgery ;
•
reimplantation for device upgrade;
•
malfunction or manufacturer advisory.
NB: Efforts should be made to prevent the need for early
reintervention during the peri-implant time period and
carefully consider when to re-enter the pocket for reasons
other than battery replacement.
DEVICE FACTORS
• abdominal generator placement;
• use epicardic leads;
• ICD e CRR have higher rate of infection than PM;
• dual-or triple-chamber device implantation have higher rate
of infection.
Implantable cardioverter–
batteriemie
defibrillators (ICD) are associated
with a greater risk of infection than
are permanent pacemakers (PPM)
Uslan DZ, et al. Permanent pacemaker and implantable
cardioverter
defibrillator
infection:
a
population-based
study. Arch Intern Med 2007; 167:669-75.
Sohail
MR,
et
al.
Risk
factor
analysis
of
permanent
pacemaker infection. Clin Infect Dis 2007;45: 166-73.
1524 pts (anni 1975-2004) – 7578
anni/persona di FU
Incidenza infezioni: 1.9/1000 anni
device.
Infezioni dei presidi
HOST FACTORS
• Fever within 24 hours before implantation;
• diabetes mellitus;
• heart failure;
• renal dysfunction;
• oral anticoagular use;
• longterm corticosteroid use;
• immunosuppressive drugs;
• underlying malignancy;
• respiratory failure;
• cerebrovascular disease;
• advanced patient age;
• female gender.
Major comorbidities
16-Year Trends in the Infection Burden for Pacemakers and Implantable Cardioverter-Defibrillators in the United States
1993 to 2008
Arnold J. Greenspon, MD,* Jasmine D. Patel,
Studio su 3410 device tra 2000-2007
Risk factors and time delay associated with cardiac device infections: Leiden device registry
J C Lekkerkerker,1 C van Nieuwkoop,2
CLASSIFICAZIONE DELLE INFEZIONI DI CIED
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INFEZIONI DELLA TASCA
– zona cutanea e sottocutanea con coinvolgimento della parte
sottocutanea degli elettrodi
– possibile erosione cutanea senza evidenza di infezione (in
paziente con danni della cute e della ferita per precedenti
trattamenti Rt, steroidei o patologie croniche dermatologiche):
la contaminazione deve essere trattata come una infezione
della tasca.
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INFEZIONI PROFONDE
– porzione intravascolare dell’elettrocatetere  generatore
– generalmente
associata
a
batteriemia
e/o
infezione
endovascolare, possibile una endocardite
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INFEZIONI SECONDARIE
– Dovute a contaminazione dell’impianto da focolai infettivi da
altre sedi (in genere infezioni tardive)
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INFEZIONI PRIMARIE
– A partenza dal CIED (generalmente dovute a contaminazione
durante le procedure di impianto, in genere precoci )
In base alla
sede di
infezione
In base al
timing di
insorgenza
The source of bacteriemia in early and late CIED
16-Year Trends in the Infection Burden for Pacemakers and Implantable Cardioverter-Defibrillators in the United States
1993 to 2008
Arnold J. Greenspon, MD,* Jasmine D. Patel,
Non c’è nessuna differenza significativa nei potenziali fattori di rischio
per l’infezione tra paziente con infezione tardiva o precoce (>12 mesi)
Microbiology of CIED infections
Microbiology of lead infections
TERAPIA ANTIBIOTICA EMPIRICA (PENDING CULTURES)
(88.7%)
MG Bongiorni et al: Microbiology of cardiac implantable electronic device infections.
Europace (2012) 14, 1334–1339
QUANDO SOSPETTARE UNA INFEZIONE DEL CIED
GENERATOR POCKET SITE
• Local pain, swelling, redness, warmth, fluctuance, wound
dehiscence, tenderness, drainage or erosion of the generator or lead
through the skin, and skin and soft-tissue ulceration (70%).
• Occasionally an early postoperative pocket hematoma can mimic
pocket infection, and distinguishing these two may be difficult.
• Close collaboration between an internist, cardiologist, and infectiousdisease specialist and careful observation of the patient may help to
avoid a premature and incorrect diagnosis of pocket infection and
unnecessary removal of the device
LEAD INFECTION:
• fever and signs of systemic infection; the lungs may also be
involved, with emboli or infection.
• Ecocardiographic findings of vegetations.
• An accurate and timely diagnosis of endovascular infection with an
intact pocket can be challenging, especially if echocardiography
shows no conclusive evidence of involvement of the device leads.
Clinical presentation of
CIED infections
Variability in Clinical Features of Early Versus Late
Cardiovascular Implantable Electronic Device Pocket
Infections
MARIKO WELCH, M.D.,* DANIEL Z. USLAN, M.D.
DIAGNOSI NON SEMPRE SEMPLICE
ESEGUIRE
• emocromo + F, VES, PCR, PTC,Tampone colturale (da materiale
purulento dalla tasca se drenata spontaneamente, evitare
aspirazione del materiale se la tasca appare gonfia e fluttuante
per non causare ulteriori contaminazioni).
• 2 SET di emocolture + 1 emocoltura da eventuale CVC.
• TEE (più attendibile del TTE) se esistono segni di infezione
sistemica, anche se emocolture negative.
• Colture intraoperatorie (se si decide la rimozione del device) per
batteri ma anche per funghi e micobatteri se il paziente è
immunodepresso o se le colture dalla tasca sono negative.
• La diagnosi potrebbe rimanere elusiva se, di fronte ad emocolture
positive, non ottenessimo TEE significativo e se la coltura della
tasca e del device fosse negativa.
Soprattutto se emocolutra positiva per S.Aureus fattori che
propendono per CIED infetto sono: emocolture positive per più di
24 ore, valvole protesiche, batteriemia entro 3 mesi dall’impianto
del device, non altri possibili focolai.
• Può essere utile (ma non dirimente) la PET, scintigrafia a leucociti
marcati o la TAC/PET (?).
TIMING DELLA TERAPIA
Sospetto di infezione di CIED
Update on Cardiovascular Implantable Electronic Device
Infections and Their Management: A Scientific Statement
From the American Heart AssociationLarry . M. Baddour
Emocolture1
Emo+, segni di inf sistemica, pregresse T
antibiotiche2
neg
Segni di inf
della tasca3
TEE
Vegetazione
valvolare
Vegetazione
sull’elettrodo
Inf del generatore
o erosione degli
elettrodi
Neg
Non
complicata
Complicato (trombosi venosa
settica, osteomielite)
Inf ≠ S
aureus
Inf da S
aureus
Sostituire
l’intero
presidio
Sostituire
l’intero
presidio
Sostituire
l’intero
presidio
Sostituire
l’intero
presidio
Sostituire
l’intero
presidio
Sostituire
l’intero
presidio
T di EI
T x 4-6w
T x 2w
T x 2-4w
T x 10-14gg
T x 7-10gg
…OCCORRE SEMPRE RIMUOVERE IL DEVICE?
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Infezione
l’impianto
antibiotica
bastare se
superficiale della ferita chirurgica precoce dopo
può esser trattata conservativamente con terapia
senza rimuovere il device (tuttavia questo non può
ci sono altri segni di infezione locali o sistemici).
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Si può lasciare il device in sede in condizioni estreme:
- alto rischio nell’intervento di rimozione per la vita del paziente;
- il paziente rifiuta la rimozione del device;
- il paziente ha un’aspettativa di vita ridotta.
In questi casi è possibile, dopo un ciclo di terapia antibiotica
parenterale ipotizzare una “long-term suppressive therapy “.
STRATEGIE PER PREVENIRE L’INFEZIONE DEL DEVICE
1) Profilassi antibiotica per gli interventi cardiochirurgici nell’adulto:
2) Pazienti colonizzati da MRSA potrebbero essere decolonizzati con
mupirocina topica dopo Tampone Nasale.
Nel 2009 uno studio randomizzato controllato doppio cieco (Cefazolina 1 g preoperatorio vs
placebo) sospeso dopo arruolamento di 649 pts/1000 pts previsti per evidenza di
superiorità della profilassi nel prevenire le infezioni (0.63% vs. 3.28%).
JC de Oliveira et al: Circ Arrhythmia Electrophysiol. 2009;2:29-34
TRATTAMENTO EMPIRICO IN ATTESA DI
DEFINIZIONE EZIOLOGICA
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Terapia antibiotica
– Vancomicina 1 g x 2 ev+ Rifampicina 300 mg x 2 per os
Oppure
– Daptomicina 6 mg/kg ev + RFP 300 mg x 2 x os
• (the Sanford Guide of antimicrobial therapy
2013)
Altri farmaci attivi su S aureus e CONS
– Linezolid 600 mg x 2 ev
– Tigeciclina 100 mg dose carico poi 50 mg x 2 die ev
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Espianto del device infetto
•
Reimpianto di un nuovo sistema
TIMING DEL REIMPIANTO
Impianto di nuovo CIED
Emo+, TEE+
Emo+, TEE-
Ripetere emocolture dopo
rimozione CIED
Ripetere emocolture dopo
rimozione CIED
Vegetazioni
valvolari
Vegetazioni su
elettrodi
Reimpianto dopo
14 gg dalla prima
emocoltura neg
Reimpianto dopo
72 h di
emocolture neg
Nuovo impianto dopo
almeno 72h di
emocolture neg
Infez tasca o erosione
elettrodi
Emo -
Emocolture neg per 72 h
Reimpianto dopo
debridment della
tasca
Baddour et al: Update on Cardiovascular Implantable
Electronic Device Infections and Their Management.
Circulation. 2010;121:458-477
QUESTIONI APERTE
• Come migliorare la qualità della diagnosi di infezione del device
(Scintigrafia/PET)?
• È utile la valutazione preoperatoria dei portatori nasali di S
aureus?
• Come ridurre i casi ad emocolture negative nonostante segni di
infezione sistemica (Maldi-ToF, biologia molecolare)?
• È ipotizzabile modificare la profilassi nei soggetti a maggior
rischio (es acido fusidico, vancomicina, daptomicina)?
Tomografia a
emissione di
positroni
• Quale è la durata ottimale della terapia antibiotica dalla
rimozione del presidio e quali markers di infezione utilizzare
(PCR, procalcitonina)?
• Quale è la durata ottimale della terapia nei casi di impossibilità di
rimozione del device
e quali markers utilizzare per il
monitoraggio?
• Quale è il timing ottimale per il reimpianto?
• Quali indicazioni di profilassi per i pazienti portatori di CIED in
caso di procedure chirurgiche (procedure odontoiatriche,
gastrointestinali, genitourinarie)?
MALDI TOF mass
spectrometer
GRAZIE DELL’ATTENZIONE E BUON LAVORO!!
CASO CLINICO
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Paziente di 83aa
Comorbilità: diabete mellito tipo2, IPB, pregresso impianto di PM
per FA a risposta ventricolare lenta.
‘99 IMA inferiore con successivo BPAC (AMIsx-IVA media e distale,
AO-DI-MO e IVP con vena safena autologa)
2002 ablazione TPSV
2007 ripresa di angina (pervietà dei Bypass, invariate le lesioni a
carico dei vasi nativi)
2009 all’ECO diagnosi di CMD ipocinetica con depressa FE=30%
2010 upgrade da PM bicamerale a ICD BIV
2011 ripresa di angina: alla CVG eseguita PTCA con stent non
medicato in graft venoso
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•
•
•
•
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11/2012 recidiva di NSTEMI ristenosi intrastent (80%) il graft
venoso trattato con PTCA+ stent
5/2013 nuovo ricovero per NSTEMI con nuovo PTCA per lesione a
vallo dello stent precedentemente posizionato (stent medicato);
all’ECO FE=20% con ipocinesia diffusa e acinesia laterale,inferiore
e apicale
Gennaio 2014 ricovero per sostituzione generatore complicato da
ematoma di tasca più grave anemizzazione; nuova procedura
coronarografica con nuova stenosi intrastent graft venoso: nuova
PTCA con stent medicato. Dimesso in duplice terapia
antiaggregante+ TAO per FA
Viene ricoverato per comparsa di sanguinamento ( da circa 20gg)
in sede di impianto ICD con decubito del generatore ed
esposizione del device viene ricoverato per espianto del ICD
eseguito in data 17/9
Dal colturale eseguito sul ICD e su elettrocateteri si isola MRSE
con il seguente ABG
Trattato dal 11/9 con VANCOMICINA (a dosaggio adattato alla
GFR e alla TDL ) + RIFAMPICINA (600mg/die e.v)
Dal colturale eseguito sul ICD e su elettrocateteri si isola MRSE con
il seguente ABG
LEVOFLOXACINA
R (≥8)
TETRACICLINA
I (2)
GENTAMICINA
R (4)
TRIMETOPRIM
S (≤10)
CLINDAMICINA
S (0.25)
ERITROMICINA
S (1)
RIFAMPICINA
R (≥4)
VANCOMICINA
S (1)
LINEZOLID
S (2)
TIGECICLINA
S (0.25)
ACIDO FUSIDICO
S (≤0.5)
OXACILLINA
R (≥4)
DAPTOMICINA
S (0.5)
Trattato dal 11/9 con VANCOMICINA (a dosaggio adattato alla GFR e
alla TDL ) + RIFAMPICINA (600mg/die e.v)
data
9/9/14
16/9/2014
17/9/2014
22/9/2014 25/9/2014 16/9/2014
GB
11330
6000
21000
9400
9960
8510
Hb
14.8
13
11.7
10.5
9.9
9.5
PTL
192000
174000
177000
251000
337000
343000
PCR #
1.4
1.1
24
108
20
16
CREAT
0.86
0.8
0.96
1.04
0.92
0.99
GFR
59.8
64.3
53.6
49.5
55.9
52.5
38
28
ccs/min
DDimero <150
TDL
Vanco *
* picco= 20-40
# <10
27
valle= 5-10
PROCALCITONIN ALGORITHMS FOR ANTIBIOTIS
THERAPY DECISION
We performed a systematic search and included all 14 randomized
controlled trials (N=4467 patients) that investigated procalcitonin
algorithms for antibiotic treatment decisions in adult patients with
respiratory tract infections and sepsis from primary care, emergency
department (ED), and intensive care unit settings.
We found no significant difference in mortality between procalcitonintreated and control patients overall (odds ratio, 0.91; 95%
confidence interval, 0.73-1.14) or in primary care (0.13; 0-6.64), ED
(0.95; 0.67-1.36), and intensive care unit (0.89; 0.66-1.20) settings
individually.
A consistent reduction was observed in antibiotic prescription and/or
duration of therapy, mainly owing to lower prescribing rates in lowacuity primary care and ED patients, and shorter duration of therapy
in moderate- and high-acuity ED and intensive care unit patients.
Arch Intern Med. 2011;171(15):1322-1331
LOW RISK/LOW ACUITY
Patients with a low pretest probability of contracting a bacterial
infection (eg, patients with nonpneumonic upper and lower respiratory
tract infection treated in the primary care setting)
MODERATE RISK/ MODERATE ACUITY
Patients who are clinically stable and are treated at the ED or are
hospitalized with pneumonia
HIGH RISK/HIGH ACUITY
ICU patients with suspected sepsis, postoperative patients in the SICU
Long-Term Suppressive Antimicrobial Therapy for Intravascular Device-Related Infections
LARRY M. BADDOUR, MD; AND THE INFECTIOUS DISEASES SOCIETY OF AMERICA’S
EMERGING INFECTIONS NETWORK
ABSTRACT: Background: Long-term suppressive antimicrobial therapy is an
alternative treatment choice in patients with medical device-related infection who are
not eligible for surgical device removal for attempted cure. There is a paucity of data
published that examines this treatment option. Methods: Members of the Infectious
Diseases Society of America’s Emerging Infections Network were polled to identify
patients with intravascular device-related infections who were not candidates for
surgery and were given long-term antimicrobial therapy to suppress clinical
manifestations of infection. Results: Clinical and microbiologic data were collected
retrospectively for 51 patients. Sixty-nine percent of patients were men; vascular
grafts were the most common type of medical device infected [30 (58.8%) patients].
Sixty-three percent (32 of 51) of cases involved Gram-positive cocci. A variety of
antimicrobials were administered as chronic suppressive therapy, with b-lactams
used most frequently (39.2%). Therapy ranged from 3 months to 10 years. Three
(7.32%) of 41 patients in whom follow-up data were available developed relapsing
infection while on long-term suppressive therapy. Three other patients suffered drug
adverse events.
CONCLUSIONS: Overall, long-term suppressive therapy was well-tolerated and
efficacious in preventing signs of infection relapse.
[Am J MedSci 2001;322(4):209–212.]