Probe-to-bone test for diagnosing diabetic foot osteomyelitis: reliable or relic?

OBJECTIVE: We sought to assess the accuracy of the probe-to-bone (PTB) test in diagnosing foot osteomyelitis in a cohort of diabetic patients with bone culture proven disease. RESEARCH DESIGN AND METHODS: In this 2-year longitudinal cohort study, we enrolled 1,666 consecutive diabetic individuals who underwent an initial standardized detailed foot assessment, followed by examinations at regular intervals. Patients were instructed to immediately come to the foot clinic if they developed a lower-extremity complication. For all patients with a lower-extremity wound, we compared the results of the PTB test with those of a culture of the affected bone. We called PTB positive if the bone or joint was palpable and defined osteomyelitis as a positive bone culture. RESULTS: Over a mean of 27.2 months of follow-up, 247 patients developed a foot wound and 151 developed 199 foot infections. Osteomyelitis was found in 30 patients: 12% of those with a foot wound and 20% in those with a foot infection. When all wounds were considered, the PTB test was highly sensitive (0.87) and specific (0.91); the positive predictive value was only 0.57, but the negative predictive value was 0.98. CONCLUSIONS: The PTB test, when used in a population of diabetic patients with a foot wound among whom the prevalence of osteomyelitis was 12%, had a relatively low positive predictive value, but a negative test may exclude the diagnosis.     

Analysis of the human VH gene repertoire. Differential effects of selection and somatic hypermutation on human peripheral CD5(+)/IgM+ and CD5(-)/IgM+ B cells.

To analyze the immunoglobulin repertoire of human IgM+ B cells and the CD5(+) and CD5(-) subsets, individual CD19(+)/ IgM+/CD5(+) or CD5(-) B cells were sorted and non-productive as well as productive VH gene rearrangements were amplified from genomic DNA and sequenced. In both subsets, the VH3 family was overrepresented largely as a result of preferential usage of a small number of specific individual family members. In the CD5(+) B cell subset, all other VH families were found at a frequency expected from random usage, whereas in the CD5(-) population, VH4 appeared to be overrepresented in the nonproductive repertoire, and also negatively selected since it was found significantly less often in the productive compared to the nonproductive repertoire; the VH1 family was significantly diminished in the productive rearrangements of CD5(-) B cells. 3-23/DP-47 was the most frequently used VH gene segment and was found significantly more often than expected from random usage in productive rearrangements of both CD5(+) and CD5(-) B cells. Evidence for selection based on the D segment and the JH gene usage was noted in CD5(+) B cells. No differences were found between the B cell subsets in CDR3 length, the number of N-nucleotides or evidence of exonuclease activity. Somatically hypermutated VHDJH rearrangements were significantly more frequent and extensive in CD5(-) compared to CD5(+) IgM+ B cells, indicating that IgM+ memory B cells were more frequent in the CD5(-) B cell population. Of note, the frequency of specific VH genes in the mutated population differed from that in the nonmutated population, suggesting that antigen stimulation imposed additional biases on the repertoire of IgM+ B cells. These results indicate that the expressed repertoire of IgM+ B cell subsets is shaped by recombinational bias, as well as selection before and after antigen exposure. Moreover, the influences on the repertoires of CD5(+) and CD5(-) B cells are significantly different, suggesting that human peripheral blood CD5(+) and CD5(-) B cells represent different B cell lineages, with similarities to murine B-1a and B-2 subsets, respectively.     

Prostatitis and urinary tract infection in men: what's new; what's true?

Urinary tract and prostatic infections are common in men, and most are treated by primary providers. Acute bacterial prostatitis is caused by uropathogens, presents with a tender prostate gland, and responds promptly to antibiotic therapy. Chronic bacterial prostatitis is a subacute infection, may present with a variety of pelvic pain and voiding symptoms, and is characterized by recurrent urinary tract infections. Effective treatment may be difficult and requires prolonged antibiotic therapy. Nonbacterial prostatitis and chronic pelvic pain syndrome are more common than bacterial prostatitis, and their etiologies are largely unknown. Treatment for both nonbacterial disorders is primarily symptomatic. An underlying anatomic or functional condition usually complicates urinary tract infections in men, but uncomplicated infections occur, often related to sexual activity. Gram-negative bacilli cause most urinary tract and prostate infections. Therapy for prostatic infections requires an agent that penetrates prostatic tissue and secretions, such as trimethoprim-sulfamethoxazole or, preferably, a fluoroquinolone. Duration of antibiotic therapy is typically 1 to 2 weeks for cystitis, 4 weeks for acute bacterial prostatitis, and 6 to 12 weeks for chronic bacterial prostatitis. Long-term suppressive antibiotic therapy and nonspecific measures aimed at palliation may be useful in selected patients with recurrent bacteriuria or persistent symptoms of chronic bacterial prostatitis.     

Is the clean-catch midstream void procedure necessary for obtaining urine culture specimens from men?

To determine whether the results of voided urine cultures in men are affected by meatal cleansing, midstream sampling, or circumcision status, 308 paired (initial and midstream) specimens were collected from 254 urology clinic patients. Half of the patients cleansed their urethral meatus with povidone-iodine prior to voiding. The circumcision status of all patients was noted. The rates of true bacteriuria (growth of 10(4) or greater colony-forming units/ml urine with a single predominant species) and contamination (growth of 10(3) or greater colony-forming units/ml urine with two or more colonial types) were compared in the various collection technique subgroups. Neither the bacteriuria nor contamination rates were significantly different (p greater than 0.05) in circumcised and uncircumcised patients, or in those who cleansed their meatus and those who did not. Contamination, but not bacteriuria, rates were higher in initial as compared with midstream specimens. These data suggest that the clean-catch midstream void procedure is unnecessary for obtaining routine voided urine culture specimens from men.     

Spectrum of toxicities of amino acid methyl esters for myeloid cells is determined by distinct metabolic pathways.

L-leucine methyl ester (Leu-OMe), Leu-Leu-OMe, Phe-OMe, and Glu-(OMe)2 are toxic to mononuclear phagocytes (M phi) and neutrophils. In the present studies, the mechanism of this toxicity was examined. A concentration of NH4Cl known to neutralize lysosomal pH and to block conversion of Leu-OMe to the dipeptide condensation product Leu-Leu-OMe inhibited Leu-OMe- or Glu-(OMe)2- but not Leu-Leu-OMe-mediated M phi toxicity. Leu-OMe-, Glu-(OMe)2-, or Leu-Leu-OMe-mediated killing of M phi was prevented by Gly-Phe-CHN2, a specific inhibitor of the thiol protease, dipeptidyl peptidase I (DPPI). Neither NH4Cl nor Gly-Phe-CHN2 prevented Phe-OMe-mediated M phi toxicity. In contrast, inhibition of M phi serine esterase activity prevented Phe-OMe- but not Leu-OMe- or Glu-(OMe)2-mediated killing of M phi. The myeloid tumor lines U937, HL60, and THP-1 were found to be uniformly enriched in DPPI and susceptible to Leu-Leu-OMe but not Leu-OMe toxicity. Whereas HL60 were resistant to Phe-OMe, THP-1 cells were killed by this agent. Incubation of peripheral blood mononuclear cells with Leu-OMe resulted in loss of natural killer (NK) functions and cytotoxic T lymphocytes (CTL) precursors, a process that requires the DPPI-dependent generation of membranolytic polymerization products. Phe-OMe had no toxic effects on NK cells or CTL precursors. These results indicate that Leu-OMe and Glu-(OMe)2 toxicity for M phi is related to the production of higher molecular weight hydrophobic polymerization products via the sequential action of two nonserine esterase lysosomal enzymes. In contrast, Phe-OMe toxicity for myeloid cells was found to correlate with serine esterase-mediated intracellular trapping of high concentrations of the free amino acid Phe. These distinct enzymatic mechanisms may provide a unique means of targeting agents capable of selectively deleting cells of myeloid lineage.     

Management of diabetic foot infections in the light of recent literature and new international guidelines

ABSTRACT

Introduction: In May 2019 the International Working Group on the Diabetic Foot (IWGDF) launched their quadrennially updated guidelines on the management of diabetic foot infections (DFIs). Concomitantly, the number of new publications regarding DFI increased.

Areas covered: The IWGDF committee developed and addressed key questions and produced evidence-based recommendations related to diagnosing and treating DFIs. This narrative review provides an overview of this new guideline and also of other recently published literature in the field of DFIs.

Expert opinion: The 2019 IWGDF guidelines provide an authoritative, international, evidence-based approach to diagnosing and treating DFIs. The 27 recommendations are supported by systematic reviews of both diagnosis and interventions. Our review of this guideline, along with other recent publications in the field, allows us to offer state-of-the-art guidance for caring for these difficult infections. As the evidence base for management of DFIs remains suboptimal, we need further research to improve the management of DFIs.     

Improving the appropriateness of vancomycin use by sequential interventions

BACKGROUND: Vancomycin usage is directly associated with the incidence of vancomycin-resistant enterococci. Optimal methods to reduce inappropriate use have not been delineated. We determined the appropriateness of vancomycin prescribing at our hospital on the basis of national guidelines and assessed the effect of sequential administrative and educational interventions. METHODS: In this prospective 3-phase study conducted in a Veterans Affairs Medical Center, we monitored vancomycin prescribing at baseline and in 2 follow-up periods. Administrative interventions included discussions with service chiefs and revising routine perioperative antibiotic prophylaxis orders. Educational interventions included in-services about vancomycin-resistant enterococci and appropriate vancomycin prescribing. In each monitoring period, 50 consecutive new vancomycin orders that could be evaluated were classified for appropriateness and categorized by indication. RESULTS: At baseline, 70% of vancomycin use was inappropriate. Surgical services accounted for 84% of orders. Interventions targeted services with high or frequently inappropriate vancomycin use. After administrative interventions, inappropriate vancomycin use dropped to 40% of orders (P =.003). Improvements were noted in targeted services. Educational interventions further decreased inappropriate vancomycin use, but the effect appeared transient. CONCLUSIONS: The simple, nonrestrictive administrative interventions used resulted in a statistically significant (30%) reduction in inappropriate vancomycin prescribing. However, educational interventions provided only transient benefit on institutional prescribing patterns.     

Association between reactive arthritis and antecedent infection with shigella flexneri carrying a 2-md plasmid and encoding an hla–b27 mimetic epitope

Objective. To determine whether Shigella flexneri strains that cause enteric infection and are associated with reactive arthritis (ReA) carry a 2-Md plasmid, pHS-2, which encodes an HLA–B27 mimetic epitope. Methods. Plasmid DNA from Shigella isolates was characterized by DNA–DNA hybridization, restriction endonuclease digestion, and sequencing. Results. S flexneri strains associated with ReA carried a 2-Md plasmid homologous to pHS-2. Conclusion. The finding of pHS-2 in additional Shigella strains associated with ReA underscores its potential importance in the etiology of the disease.