Discordance between serum CRP and ESR is not uncommon (1,2). This phenomenon may be due to a variety of factors including the fact that the kinetics of these two tests is quite different, as discussed under “Should I order C-reactive protein (CRP) or erythrocyte sedimentation (ESR) on patients suspected of having a new infection?” in this blog. In a study of CRP/ESR discordance (defined as results differing by 2 or 3 quartiles) in adults, a high CRP/low ESR profile was more likely to be associated with urinary, GI, blood stream, and pulmonary infections, myocardial infarction, and venous thromboembolism and less likely to be associated with bone and joint infections (1). In the same study, a high ESR/low CRP was associated with connective tissue diseases, such as systemic lupus erythematosus and strokes (1).
1. Feldman M, Aziz B, Kang GN, et al. C-reactive protein and erythrocyte sedimentation rate discordance: frequency and causes in adults. Translational Research 2013;161:37-43.
2. Colombet I, Pouchot J, Kronz V. Agreement between erythrocyte sedimentation rate and C-reactive protein in hospital practice. Am J Med 2010;123:864.e7-863.e13.
An uncommon but serious side effect of FQs (e.g. ciprofloxacin, levofloxacin, and moxifloxacin) is Achilles tendon rupture. A putative mechanism for this adverse effect is inhibition of host mitochondrial components (1). Recall that mitochondria, the ATP-generating machine within our cells, are thought to be archaic bacterial ancestors that have co-evolved with us. Quinolones are inhibitors of bacterial gyrases and topoisomerases and also appear to be associated with DNA degradation of the mitochondria in some mammalian cells. In vitro, FQs appear to have a tropism for mitochondria in tenocytes, chondrocytes, and osteoblasts. Thus, it is possible that at least in some patients (e.g. those ≥60 years of age, on higher doses of corticosteroids, or with several renal disease or other idiosyncratic factors) the mitochondrial damage is sufficient to cause serious injury to the Achilles tendon (2).
1. Barnhill AE, Brewer MT, Carlson SA. Adverse effects of antimicrobials via predictable or idiosyncratic inhibition of host mitochondrial components. Antimicrob Agents Chemother 2012;56:4046-4051.
2. Shakibaei M, Stahlmann R. Ultrastructure of Achilles tendon from rats after treatment with fleroxacin. Arch Toxicol 2001;75:97-102.
The finding of normal serum albumin in cirrhotic patients is not at all uncommon. In fact, in a meta-analysis involving 8 published articles, the sensitivity of serum albumin (< 3.5 g/dL) in cirrhosis was only 45% (1). It turns out that in many patients with cirrhosis, the synthetic ability of liver with respect to albumin appears well preserved until more advanced stages of liver dysfunction develop (2). So don’t exclude cirrhosis just because serum albumin is normal.
1. Udell JA, Wang CS, Tinmouth J et al. Does this patient with liver disease have cirrhosis? JAMA 2012;307:832-842.
2. Ballmer PE, Washe D. McNurlan M, et al. Albumin synthesis rates in cirrhosis: correlation with Child-Turcotte classification. Hepatology 1993;18:292-297.
There is relative dearth of data addressing this very important issue. A decreased IG response after mitogen stimulation during treatment with oral prednisolone has been reported (1). In a study of patients with autoimmune disorders, 27% of patients on daily prednisolone dose of 10 mg or more had indeterminate QuantiFeron Gold In-Tube test compared to 1% of patients not taking prednisolone (1). A meta-analysis of the performance of IGRAs (including T-SPOT.TB) concluded that these assays were negatively affected by immunosuppressive therapy (2). So, until more data becomes available, caution is advised in interpreting lack of positive test or indeterminate results of IGRAs in patients on corticosteroid therapy.
1. Belard E, Semb S, Ruhwald M, et al. Prednisolone treatment affects the performance of the QuantiFERON Gold In-Tube test and the Tuberculin skin test in patients with autoimmune disorders screened for latent tuberculosis infection. Inflamm Bowel Dis 2011;17:2340-2349.
2. Shahidi N, Fu Y-T, Qian H, et al. Performance of interferon-gamma release assays in patients with inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis 2012;18:2034-2042.
Actually no! In fact, a recent study of CAP from Netherlands demonstrated that empiric treatment with beta-lactam monotherapy was not inferior to strategies using a beta-lactam-macrolide combination or fluoroquinolone monotherapy with regard to 90-day mortality, or length of hospital stay (1). To help exclude Legionella pneumonia (often accounting for <5% of CAP), urine Legionella antigen was routinely performed. So once Legionella has been reasonably excluded, unless suspicion for other atypical causes of CAP (i.e. Mycoplasma pneumoniae or Chlamydophila pneumoniae) remains high, empiric monotherapy with a beta-lactam (e.g. ceftriaxone) may be reasonable in many cases of CAP.
1. Postma DF1, van Werkhoven CH, van Elden LJ, et al. CAP-START Study Group Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med. 2015;372:1312-23.
2. von Baum H, Ewig S, Marre R, et al. Competence Network for Community Acquired Pneumonia Study Group. Community-acquired Legionella pneumonia: new insights from the German competence network for community acquired pneumonia. Clin Infect Dis 2008;46:1356.
Contributed by Jessica A. Hennessey, MD, PhD, Boston, MA
Yes, it is! Ceftriaxone has excellent activity against MSSA . In a retrospective study comparing ceftriaxone to oxacillin for osteoarticular infections due to MSSA, there was no difference in treatment success at 3-6 and > 6 months following completion of IV antibiotics; oxacillin had to be discontinued more often due to toxicity, however (1). In another retrospective study comparing cefazolin to ceftriaxone for treatment of MSSA infections ( ≥50% of patients with osteomyelitis), favorable outcomes, adverse events and complications were similar between the 2 groups (2).
1. Wieland BW, Marcantoni JR, Bommarito KM, et al. A retrospective comparison of ceftriaxone versus oxacillin for osteoarticular infections due to methicillin-susceptible Staphylococcus aureus. Clin Infect Dis 2012;54:585-590
2. Winans SA, Luce Am, Hasbun R. Outpatient parenteral antimicrobial therapy for the treatment of methicillin-susceptible Staphylococcus aureus: a comparison of cefazolin and ceftriaxone. Infection 2103;41:769-774.
Not as good as one would hope. In an often quoted study involving 768 patients with suspected PE who underwent angiography, a combination of normal A-a gradient (<20 mm Hg ), normal PaO2 (>80 mm Hg), and normal PaCO2 (>35 mm Hg) was examined to help exclude PE (1). Among patients with no known cardiopulmonary disease and normal values in all 3 parameters, over 30% still had PE, while among those with cardiopulmonary disease and normal parameters 17% had PE. In short, normal arterial blood gases may make PE less likely, they do not by any means exclude the possibility of PE.
1.Stein PD, Goldhaber SZ, Henry JW, et al. Arterial blood gas analysis in the assessment of suspected acute pulmonary embolism. CHEST 1996; 109:78-81.