the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44(suppl 2):S27–72. Correspondence: Michael S. Abers, BA, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 ([email protected]). Clinical Infectious Diseases 2014;58(12):1782–3 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/ciu140

TO THE EDITOR—The placement of an antibiotic-impregnated cement spacer (ACS) during a staged replacement of an infected prosthetic joint is frequently used to increase antibiotic concentration in the joint capsule, and the 2012 Infectious Diseases Society of America Clinical Practice Guidelines for management of prosthetic joint infections state that systemic toxicity from antibiotic-impregnated cement rarely occurs [1]. However, a recent retrospective study found that

tobramycin-containing ACS. Approval for this study was obtained from the Vanderbilt Institutional Review Board. Ten patients were identified with an acute rise in serum creatinine and a detectable serum tobramycin level following placement of a tobramycin-containing ACS out of total of 46 revision arthroplasties with ACS placement performed at our institution during this period (Table 1). Patients ranged in age from 50 to 83 years and 6 were male. All patients had comorbid conditions that could predispose to postoperative renal dysfunction as well as perioperative interventions that may have increased the risk of renal dysfunction (Table 1). All patients also received concomitant oral or parenteral antibiotics, but none received systemic aminoglycosides. All ACSs contained tobramycin (mean dose, 8.2 g), and 9 of 10 also contained vancomycin (mean dose, 7.6 g). The average postoperative increase was 260% of the baseline creatinine and occurred early in the postoperative course (range, postoperative day 1–11). All patients tested had detectable serum tobramycin (mean level, 3.3 µg/mL [range, 0.1–19.8

Table 1. Patient Characteristics, Serum Tobramycin Level, and Postoperative Creatinine Change

Case Sex a

Age, y

Risk Factors for Kidney Injury

Joint

Infecting Organism

Oral or IV Antibioticsb

Preoperative Creatinine, mg/dL

Peak Postoperative Creatinine (% Increase)

Tobramycin Spacer Dose, g

Serum Tobramycin Level, µg/mL/ POD

Vancomycin Spacer Dose, g

1

F

66

HTN, SLE

Knee Unknown

LF, DN

1.6

3.8 (138%)

9.6

19.8/1

8

2

M

50

RA, NSAIDs

Knee S. aureus

VM, RN, DN

0.9

2.3 (156%)

12

1.3/11

10

3

M

63

DM, HTN, CKD

Knee Unknown

CF, DN, LZ

2.2

4.8 (118%)

9.6

3.6/3

0

4

M

76

DM, TF, VP

Knee S. aureus

NC, RN, MF, CF

1.8

9.3 (417%)

4.8

1.1/3

4

5

M

82

HTN

Knee Unknown

VM, DN

0.8

2.4 (200%)

9.6

1.9/8

8

6

F

74

DM, HTN, IV contrast

Hip

Group B Streptococcus

LF, DN

0.8

1.7 (113%)

4.8

0.3/2

5

7

M

62

DM, HTN

Hip

Unknown

NC, VM, RN

1.4

2.3 (64%)

2.4

0.1/3

9

8

M

65

DM, HTN, TF, VP, Knee Unknown NSAIDs

CZ, CX, VM, CF, DN

0.7

4.1 (486%)

9.6

2.4/9

8

9

F

83

CAD, HTN, TF, VP Knee PA, KO, CoNS, CP

VM, CF, DN

1.1

1.8 (64%)

9.6

0.7/9

8

10

F

51

CAD, HTN, TF, VP Knee Unknown

CF, VM, DN

0.9

8.5 (844%)

9.6

2.0/7

8

Abbreviations: CAD, coronary artery disease; CF, ciprofloxacin; CKD, chronic kidney disease; CoNS, coagulase-negative Staphylococcus; CP, Clostridium perfringens; CX, ceftriaxone; CZ, cefazolin; DM, diabetes mellitus; DN, daptomycin; HTN, hypertension; IV, intravenous; KO, Klebsiella oxytoca; LF, levofloxacin; LZ, linezolid; MF, micafungin; NC, nafcillin; NSAID, nonsteroidal anti-inflammatory drug; PA, Pseudomonas aeruginosa; POD, postoperative day; RA, rheumatoid arthritis; RN, rifampin; SLE, systemic lupus erythematosus; TF, blood transfusion; VM, vancomycin; VP, vasopressors. a Index patient. b List may represent sequential selection of antibiotics in response to culture data or toxicity concerns.

CORRESPONDENCE



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Detectable Serum Tobramycin Levels in Patients With Renal Dysfunction and Recent Placement of Antibiotic-Impregnated Cement Knee or Hip Spacers

higher doses of tobramycin in the spacer cement were associated with increased risk of acute kidney injury (AKI) [2–4]. An estimated 1%–2% of the >725 000 total knee and hip arthroplasties performed yearly in United States hospitals become infected over the duration of use [5, 6]; therefore, complications from ACSs could be an important source of postoperative morbidity. A patient developed renal insufficiency after receiving a tobramycin-containing ACS and was found to have a serum tobramycin level of 19.8 µg/mL shortly after surgery and a level of 3.0 µg/mL 4 weeks later with no systemic aminoglycoside administration. To investigate this further, we identified patients with postoperative AKI and detectable serum tobramycin levels after receiving an ACS during 2-stage arthroplasty revision. Between February 2011 and April 2012, physicians on the inpatient infectious diseases consultation service were asked to measure serum tobramycin concentrations in patients with a >50% rise in serum creatinine from the preoperative baseline following placement of a

6. Kurtz SM, Lau E, Schmier J, Ong KL, Zhao K, Parvizi J. Infection burden for hip and knee arthroplasty in the United States. J Arthroplasty 2008; 23:984–91.

Note

TO T HE EDITOR—Rhinovirus (RV) is a common causative agent of acute infections. In addition to the common cold, RV infection is associated with acute otitis media, sinusitis, bronchiolitis, asthma, pneumonia, and severe infections, especially in immunocompromised patients [1]. RV infection in patients with chronic obstructive pulmonary disease may cause mortality [2]. In otherwise healthy subjects, RV shedding lasts 7–13 days [3]. No antiviral drug for RV infection is in clinical use. We have shown that RV may induce persistent lower respiratory tract infections in patients with hypogammaglobulinemia [3, 4]. In addition, chronic RV infections have been reported in lung transplant recipients [5] and during cystic fibrosis [6]. Because RV has been observed to be susceptible to the action of interferon α [7] and because ribavirin potentiates the antiviral effect of interferon α, we treated RV infections in 4 patients who had hypogammaglobulinemia with pegylated interferon α2a and ribavirin. Three adult patients had common variable immunodeficiency disease, and 1 adult patient had X-linked agammaglobulinemia (Table 1). Despite receipt of adequate immunoglobulin replacement therapy, they all had a history of recurrent or chronic RV infection [4]. Episodes of

Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Michael J. Noto, John R. Koethe, Geraldine Miller, and Patty W. Wright Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee

References 1. Osmon DR, Berbari EF, Berendt AR, et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2013; 56: e1–25. 2. Curtis JM, Sternhagen V, Batts D. Acute renal failure after placement of tobramycinimpregnated bone cement in an infected total knee arthroplasty. Pharmacotherapy 2005; 25:876–80. 3. Dovas S, Liakopoulos V, Papatheodorou L, et al. Acute renal failure after antibioticimpregnated bone cement treatment of an infected total knee arthroplasty. Clin Nephrol 2008; 69:207–12. 4. Menge TJ, Koethe JR, Jenkins CA, et al. Acute kidney injury after placement of an antibioticimpregnated cement spacer during revision total knee arthroplasty. J Arthroplasty 2012; 27:1221–7. e1–2. 5. DeFrances CJ, Lucas CA, Buie VC, Golosinskiy A. 2006 National Hospital Discharge Survey. Natl Health Stat Report 2008; 1–20.

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Correspondence: Michael J. Noto, MD, PhD, Division of Infectious Diseases, Vanderbilt University School of Medicine, A2200 Medical Center North, 1161 21st Ave S, Nashville, TN 37232 ([email protected]). Clinical Infectious Diseases 2014;58(12):1783–4 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/ciu159

Treatment of Persistent Rhinovirus Infection With Pegylated Interferon α2a and Ribavirin in Patients With Hypogammaglobulinemia

CORRESPONDENCE

earlier RV infections in these patients served as self-controls during study of the duration of RV shedding after treatment. Three patients had developed bronchiectasis. At the time of treatment, all patients had respiratory symptoms. For all cases, RV was detected by culture of sputum specimens and by polymerase chain reaction analysis of nasal swab and sputum specimens. After patients provided oral informed consent, we treated them with 180 µg of pegylated interferon α2a (Pegasys, Roche, Welwyn Garden City, United Kingdom) subcutaneously once weekly and with 400 mg of ribavirin (Rebetol, MSD, Hertfordshire, United Kingdom) orally twice daily for 2 weeks. We found that interferon α2a and ribavirin treatment was associated with rapid decrease and clearance of RV RNA during the case episodes, compared with the self-control episodes. The efficacy of treatment was exemplified by the rapid increase of blood antiviral MxA levels (Supplementary Figure) [8]. Because of chronic respiratory symptoms and concomitant use of antibiotics, the clinical outcome was difficult to adjust. However, 3 patients reported improved quality of life after treatment. Two patients reported fever as an interferon-induced adverse effect. It is of note that all 4 patients developed RV infection 2–12 months after completion of treatment. The cause of the increased susceptibility of patients with hypogammaglobulinemia to RV infection is unknown [4]. Low levels of MxA before treatment suggest deficient RV-induced interferon induction, which has been reported in subjects with asthma and chronic obstructive pulmonary disease [2]. On the other hand, exogenous interferon induced good levels of MxA, suggesting a normal IFN signaling pathway [9]. Interestingly, Falzarano et al [10] recently reported that interferon α2b and ribavirin treatment induced distinct gene expression, reduced viral replication, reduced levels of serum and lung proinflammatory markers, and improved

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µg/mL]). Of the 9 patients with subsequent laboratory values, serum creatinine levels normalized after an average of 15.9 days postoperatively (range, 10–26 days). The data provide evidence of systemic tobramycin absorption from ACSs placed during revision joint arthroplasty. This finding suggests that patients receiving an ACS may have prolonged exposure to elevated serum aminoglycoside levels, which could increase the risk of toxicity, including nephrotoxicity. Prospective studies are warranted to determine the true incidence of systemic aminoglycoside absorption from ACSs and the operative and patient risk factors that lead to nephrotoxicity.

Detectable serum tobramycin levels in patients with renal dysfunction and recent placement of antibiotic-impregnated cement knee or hip spacers.

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