Data about the required duration of intravenous therapy for suppurative thrombophlebitis is lacking. Among 36 episodes of proven suppurative thrombophlebitis requiring hospital admission, no relapses occurred when treatment was given for >7 days intravenously and followed by oral therapy. A <4-week course of intravenous antibiotics may be sufficien

Battega, Manuel

Fluckiger, Ursula

Khanlari, Bettina

Mertz, Dominik

Viktorin, Nina

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BRIEF REPORT • CID 2008:46 (1 March) • 741B R I E F R E P O R TTable 1. Demographic and clinical characteristics at hospitaladmission of 29 patients with 36 episodes of suppurativethrombophlebitis.Variable ValueAge, median years (range) 33 (20–45)Male sex, no. (%) of episodes 22 (61.1)Chronic hepatitis C, no. (%) of episodes 30 (88.9)HIV positivity, no. (%) of episodes 4 (11.1)C-reactive protein level, median mg/dL (range) 162.5 (6–417)Leukocyte count, median cells  109 (range) 12 (5.2–31)Temperature, median C (range) 39.1 (35.3–41.3)Less than 28 Days of IntravenousAntibiotic Treatment Is Sufficientfor Suppurative Thrombophlebitisin Injection Drug UsersDominik Mertz, Bettina Khanlari, Nina Viktorin, Manuel Battegay,and Ursula FluckigerDivision of Infectious Diseases and Hospital Epidemiology, University HospitalBasel, Basel, SwitzerlandData about the required duration of intravenous therapy forsuppurative thrombophlebitis is lacking. Among 36 episodesof proven suppurative thrombophlebitis requiring hospitaladmission, no relapses occurred when treatment was givenfor 17 days intravenously and followed by oral therapy. A!4-week course of intravenous antibiotics may be sufficient.Suppurative thrombophlebitis of proximal veins caused by non-sterile injections is a potentially life-threatening condition thatis common among injection drug users (IDUs) [1]. In contrastwith catheter-related thrombophlebitis and Lemierre syndrome[2, 3], little attention is paid to the antibiotic management ofsuppurative thrombophlebitis [4]. Staphylococcus aureus is thepredominant bacteria in suppurative thrombophlebitis of IDUs[5, 6]. In general, conservative antibiotic treatment is recom-mended for suppurative thrombophlebitis of large veins [5, 6].However, the duration and route of administration of antibiotictreatment are uncertain, and experts recommend that therapybe given according to published endocarditis-treatment guide-lines [7]. However, a 4-week course of intravenous therapy isoften not feasible for IDUs [6]. A 2-week course of intravenoustherapy followed by oral ciprofloxacin plus rifampicin, admin-istered according to the guidelines for treatment of right heartendocarditis due to S. aureus in IDUs [8], seems to be analternative [6], but widespread use of this regimen may beReceived 24 August 2007; accepted 29 October 2007; electronically published 30 January2008.Reprints or correspondence: Dr. Ursula Flu¨ckiger, Div. of Infectious Diseases and HospitalEpidemiology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland(flueckigerU@uhbs.ch).Clinical Infectious Diseases 2008; 46:741–4 2008 by the Infectious Diseases Society of America. All rights reserved.1058-4838/2008/4605-0015$15.00DOI: 10.1086/527445difficult, because IDUs are frequently noncompliant to regi-mens that require that they reliably take oral medications.In a retrospective survey of infectious complications among344 admissions of IDUs at our hospital (University HospitalBasel; Basel, Switzerland), we diagnosed a suppurative throm-bophlebitis in 36 cases (11%). In the present study, we analyzethe clinical course, duration of antibiotic therapy, and outcomein these 36 cases of suppurative thrombophlebitis.Methods. We included all IDUs who were hospitalized forsuppurative thrombophlebitis from January 2001 through De-cember 2006 and evaluated by the infectious diseases serviceof the University Hospital Basel, a 780-bed primary and tertiarycare center with ∼27,000 hospital admissions annually. De-mographic and clinical data were extracted from hospital charts,laboratory results, and separate reports of the infectious diseasesservice. The study was approved by the ethics committee ofUniversity Hospital Basel. The diagnosis of suppurative throm-bophlebitis was defined by either 2 positive blood cultureresults or bacteria detected in the thrombus in a patient withnegative blood culture results and detection of a thrombus byCT or ultrasonography [3, 9].Results. Thirty-six hospital admissions for suppurativethrombophlebitis were identified among 29 IDUs (2 readmis-sions to the hospital were considered to be relapses, and 5readmissions were not). Patient characteristics at hospital ad-mission are listed in table 1. Twenty-nine cases (80.6%) met2 systemic inflammatory response syndrome criteria [10] athospital admission.Thrombosis was detected on the basis of ultrasonographicfindings in 32 cases (89%) and on the basis of CT findings in4 cases (11%). Transthoracic echocardiography was performedin 31 (86%) of 36 cases; additional transesophageal echocar-diography was performed in 5 of these 31 cases. Infective en-742 • CID 2008:46 (1 March) • BRIEF REPORTTable 2. Characteristics of suppurative thrombophlebitis.VariableNo. (%)of episodes(n p 36)LocationFemoral vein 21 (58.3)Iliac vein 7 (19.4)Great saphenous vein 2 (5.6)Internal jugular vein 5 (13.9)Subclavian vein 1 (2.8)Predominant pathogenaStaphylococcus aureus 19 (52.8)Streptococcus pyogenes 7 (19.4)Viridans streptrococci 3 (8.3)Streptococcus dysgalactiae 3 (8.3)Streptococcus agalactiae 1 (2.8)Peptostreptococcus asacharolyticus 2 (5.6)Arcanobacterium hemolyticum 1 (2.8)a Additional pathogens in polymicrobial infections were Fusobacterium nec-rophorum, Micromonas micros, Actinomyces species, and Veillonella species.docarditis was diagnosed in 3 cases. Because transthoracic echo-cardiography cannot definitely rule out endocarditis, some casesof infective endocarditis may have been missed.Thromboses were located mainly in the femoral and the iliacvein (table 2). The left side of the body was affected morefrequently (21 cases; 58.3%).In 160 (71.4%) of a total of 224 blood samples obtainedwithin 48 h after hospital admission, the predominant pathogenwas cultured. In all but 10 cases,3 blood samples with positiveculture results were obtained. S. aureus was the most frequentpredominant pathogen (in 19 [53%] of the cases), followed bystreptococci (table 2). No methicillin-resistant S. aureus isolateswere identified. In 12 cases, polymicrobial sepsis was diagnosed.In 1 case with negative blood culture results (in which only 1pair of blood samples was obtained), a thrombectomy wasperformed, and S. aureus was cultured from the biopsy spec-imen. In all cases, intravenous antibiotic therapy was admin-istered as first-line therapy. All but 1 case received b-lactamantibiotics as the main antibiotic therapy (i.e., the antibioticgiven for the longest period intravenously) (table 3).The duration of intravenous therapy varied greatly (table 3).Four patients were treated for 7 days; 2 of these patientsexperienced relapse leading to readmission (after 3 days andafter 5 days). There were no relapses among the patients whowere treated intravenously for 17 days. Six patients were treatedfor 8–14 days, and 10 patients were treated for 15–21 days.Altogether, in 20 (56%) of the episodes, the patients receivedan intravenous therapy for 21 days. The median duration ofintravenous therapy was 19.5 days. In 9 cases, therapy wascontinued 128 days because of additional complications. Asubsequent regimen of oral antibiotic therapy was administeredin 34 of 36 cases. The median duration of oral treatment was9.5 days (range, 0–180 days), and the overall duration of an-tibiotic therapy was a median of 28.5 days (range, 7–220 days).There was no significant difference in the duration of intra-venous therapy between patients treated for S. aureus infectionand those treated for non–S. aureus infection. Documentednegative blood culture results at day 3 of therapy did not in-fluence the duration of intravenous antibiotic treatment (me-dian duration of therapy was 22 days and 21.5 days for patientswith negative and patients with positive blood culture results,respectively).In 33 (91.7%) of the cases, anticoagulation therapy was ini-tiated. In 10 cases (27.8%), oral anticoagulation therapy wasabandoned at hospital discharge because of complianceconcerns.Additional complications associated with IDU were as fol-lows: local skin abscesses in 14 cases (22.2%; incisions weremade in 8 cases); septic arthritis in 2 cases (5.6%; lavage wasnecessary); 1 case of necrotizing fasciitis after suppurativethrombophlebitis of the subclavian vein, resulting in amputa-tion of the limb; 2 cases of acute osteomyelitis; 5 cases ofpulmonary abscesses; and 2 cases of empyemas. In addition tothese 11 cases that required surgical intervention because ofadditional complications, only 1 case involved a patient whounderwent surgery of the involved vein; this patient experi-enced a local abscess formation that required excision of theinternal jugular vein.The median duration of hospitalization was 20 days (range,6–58 days), and the median time to defervescence was 2 days(range, 0–17 days). Negative blood culture results were obtainedat follow-up in 28 cases (77.8%). The median time from startof therapy to the first negative blood culture result was 4.5 days(range, 2–167 days).The overall readmission rate was high (table 4). However,only 2 readmissions were attributable to relapses of suppurativethrombophlebitis. According to the death records of the localauthorities, no patient died after hospital discharge.Discussion. Suppurative thrombophlebitis is a potentiallydangerous complication in IDUs. No studies or clinical trialshave investigated the optimal duration of intravenous antibiotictreatment. Four weeks of therapy is recommended accordingto expert opinions [7]. A long hospital stay for intravenoustherapy may not be feasible because of compliance and ad-herence problems in IDUs [11]. In our study, the intravenousantibiotic treatment duration was quite variable, ranging from!7 days to 128 days. No relapse occurred in cases treated in-travenously for 17 days. In more than one-half of the episodes(20 episodes; 56%), the patient received intravenous therapyfor21 days. The present data suggests that a 2–3-week courseof intravenous therapy followed by therapy with oral antibioticswas safe for suppurative thrombophlebitis. Adherence in IDUsBRIEF REPORT • CID 2008:46 (1 March) • 743Table 3. Therapy for suppurative thrombophlebitis.VariableSuppurativethrombophlebitisepisodes(n p 36)Main antibioticaAmoxicillin-clavulanate 12 (33.3)Penicillin 12 (33.3)Flucloxacillin 9 (25.0)Piperacillin-tazaobactam 1 (2.8)Imipenem-cilastatin 1 (2.8)Vancomycin 1 (2.8)Duration of intravenous therapyOverallMedian days (range) 19.5 (6–85)7 Days 4 (11.1)8–14 Days 6 (16.7)15–21 Days 10 (27.8)22–28 Days 7 (19.4)128 Days 9 (25)For Staphylococcus aureus infectionbNo. of episodes 19Median days (range) 23 (6–85)For non–S. aureus infectionbNo. of episodes 17Median days (range) 18 (7–41)Duration of oral therapy, median days (range) 9.5 (0–180)NOTE. Data are no. (%) of episodes, unless otherwise indicated.a Main antibiotic was considered to be the antibiotic given for the longestperiod intravenously.b for differences between groups, using 2-tailed Mann-WhitneyPp .837U test.Table 4. Outcome of suppurative thrombophlebitis.VariableNo. (%)of episodes(n p 36)Negative blood culture resultsAvailable 28 (77.8)Obtained during therapy 23 (63.9)Hospital readmissionOverall 28 (77.8)Relapse 2 (5.6)is known to be limited. Therefore, it remains uncertain whetherthe oral medications were taken.Two or more systemic inflammatory response syndrome cri-teria [10] were met by 29 cases (80.6%) at hospital admission,emphasizing the severity of illness and confirming that IDUstend to present late in the course of illness. In accordance withthe literature, we found no attributable mortality. A recentreview involving 115 patients showed a mortality rate of !2%[4].We identified S. aureus as the pathogen most frequently cul-tured, which is in accordance with the findings of other studies[5]. S. aureus is one of the most frequently isolated pathogensin infective right-heart endocarditis among IDUs [8]. There-fore, empirical therapy for IDUs with suspected suppurativethrombophlebitis or infective endocarditis should cover thispathogen. In our region, methicillin-resistant S. aureus is rare[12]; therefore, empirical treatment with amoxicillin-clavulan-ate or flucloxacillin is sufficient.Most septic thromboses were identified in veins of the lowerlimbs (83.3%). This might be explained by the use of less hy-gienic injection techniques when injecting in the lower limbs,compared with injection techniques used in the upper limbs.Only 1 suppurative thrombophlebitis was identified in the up-per subclavian vein, which may reflect metastatic infection.An excision of the vein was performed in only 1 patient whopresented with an abscess formation. The other 35 cases weresuccessfully treated with antibiotic and anticoagulation therapy.In the literature, conservative management is proposed for sup-purative thrombophlebitis of large veins, whereas the failure ofconservative therapy and catheter-related or suppurativethrombophlebitis of small peripheral veins are indications forsurgical intervention [5, 6].Our data are not sufficient to make a recommendation con-cerning anticoagulation in IDUs with suppurative thrombo-phlebitis, which is still under discussion. A recently publishedsystematic review showed that there is a lack of comparativetrials studying the effectiveness and toxicity of heparin in pa-tients with suppurative thrombophlebitis [4]. In our study, allbut 3 patients received anticoagulation therapy during hospi-talization; the 3 patients who did not receive anticoagulationtherapy received low–molecular weight heparin in prophylacticdoses.A limitation of our study is the use of a retrospective analysiswith a limited number of cases. Nevertheless, our study is, toour knowledge, the largest case series reported to date. A furtherstrength of our study is the exact information about outcomeparameters: IDUs in our area are not likely to be admitted toany other hospitals, and death records from local authoritieswere available, precluding the possibility that any deaths oc-curred as consequences of relapses without our knowledge.Also, it is extremely unlikely that we have missed any IDUswith suppurative thrombophlebitis during the observation pe-riod in our hospital, because the infectious diseases serviceevaluates all patients with positive blood culture results. There-fore, any selection bias is unlikely.The present data suggest that suppurative thrombophlebitiscould be sufficiently treated with an intravenous antibioticcourse of 14–21 days followed by oral therapy. This observationshould be evaluated in a prospective randomized study com-paring short regimens versus longer regimens.744 • CID 2008:46 (1 March) • BRIEF REPORTAcknowledgmentsFinancial support. The Margarete and Walter Lichtenstein Foundation(unrestricted educational grant to N.V.) and the Stiftung Forschung In-fektionskrankheiten, Basel (unrestricted education grant to D.M.).Potential conflicts of interest. All authors: no conflicts.References1. Scheidegger C, Zimmerli W. Incidence and spectrum of severe medicalcomplications among hospitalized HIV-seronegative and HIV-sero-positive narcotic drug users. AIDS 1996; 10:1407–14.2. Andes DR, Urban AW, Acher CW, Maki DG. Septic thrombosis of thebasilic, axillary, and subclavian veins caused by a peripherally insertedcentral venous catheter. Am J Med 1998; 105:446–50.3. Chirinos JA, Garcia J, Alcaide ML, Toledo G, Baracco GJ, LichtsteinDM. Septic thrombophlebitis: diagnosis and management. Am J Car-diovasc Drugs 2006; 6:9–14.4. Falagas ME, Vardakas KZ, Athanasiou S. Intravenous heparin in com-bination with antibiotics for the treatment of deep vein septic throm-bophlebitis: a systematic review. Eur J Pharmacol 2007; 557:93–8.5. Kniemeyer HW, Grabitz K, Buhl R, Wust HJ, Sandmann W. Surgicaltreatment of septic deep venous thrombosis. Surgery 1995; 118:49–53.6. Fah F, Zimmerli W, Jordi M, Schoenenberger RA. Septic deep venousthrombosis in intravenous drug users. Swiss Med Wkly 2002; 132:386–92.7. Mermel LA, Farr BM, Sherertz RJ, et al. Guidelines for the managementof intravascular catheter-related infections. Clin Infect Dis 2001; 32:1249–72.8. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: di-agnosis, antimicrobial therapy, and management of complications: astatement for healthcare professionals from the Committee on Rheu-matic Fever, Endocarditis, and Kawasaki Disease, Council on Cardio-vascular Disease in the Young, and the Councils on Clinical Cardiology,Stroke, and Cardiovascular Surgery and Anesthesia, American HeartAssociation: endorsed by the Infectious Diseases Society of America.Circulation 2005; 111:394–434.9. Cohen Y, Tit A, Brauner M, Fosse JP, Hoang P. Contribution of com-puterized tomography to the diagnosis of catheter-induced septic cen-tral venous thrombosis. Intensive Care Med 1996; 22:1279–80.10. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organfailure and guidelines for the use of innovative therapies in sepsis. TheACCP/SCCM Consensus Conference Committee. American College ofChest Physicians/Society of Critical Care Medicine. Chest 1992; 101:1644–55.11. Dans PE, Matricciani RM, Otter SE, Reuland DS. Intravenous drugabuse and one academic health center. JAMA 1990; 263:3173–6.12. Mertz D, Frei R, Jaussi B, et al. Throat swabs are necessary to reliablydetect carriers of Staphylococcus aureus. Clin Infect Dis 2007; 45:475–7.

Less than 28 Days of Intravenous Antibiotic Treatment Is Sufficient for Suppurative Thrombophlebitis in Injection Drug Users

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