Ulrich Seybold

Hematogenous osteomyelitis mimicking osteosarcoma due to Community Associated Methicillin-Resistant Staphylococcus aureus.

Community Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen with increasing clinical significance. Initially recognized as a cause of skin and soft tissue infections, it has soon been shown to cause life threatening illnesses. We describe two cases of osteomyelitis of the femur in young otherwise healthy adults. Initially a preliminary diagnosis of osteosarcoma was suggested by radiologic studies and both patients underwent an excisional biopsy. Following identification of the pathogen as CA-MRSA (Panton-Valentine leukocidin positive USA300 clone), both patients were successfully treated with prolonged courses of vancomycin.

Impact of changes in antigen level on CD38/PD‐1 co‐expression on HIV‐specific CD8 T cells in chronic, untreated HIV‐1 infection

Excessive immune activation is a hallmark of chronic uncontrolled HIV infection. During the past years, growing evidence suggests that immune inhibitory signals also play an important role in progressive disease. However, the relationship between positive and negative immune signals on HIV‐specific CD8 T cells has not been studied in detail so far in chronic HIV‐1 infection. In this study, the expression of markers of positive (CD38) and negative (PD‐1) immune signals on virus‐specific CD8 T cells in chronic, untreated HIV‐1 infection was evaluated using intracellular cytokine staining. Viral escape mutations were assessed by autologous virus sequence analysis and subsequent peptide titration assays. Single‐epitope CD8 T‐cell responses toward Gag, Pol, and Nef were compared in 12 HIV‐1 controllers (viral load <5,000 cp/ml) and 12 HIV‐1 progressors (viral load >50,000 cp/ml) and a highly significant increase of CD38/PD‐1 co‐expression on virus‐specific CD8 T cells in progressors was found (P < 0.0001). The level of CD38/PD‐1 co‐expression was independent of epitope specificity. Longitudinal follow‐up revealed a clear drop in CD38/PD‐1 co‐expression on virus‐specific CD8 T cells after the suppression of antigen following either viral escape mutation or the initiation of HAART (P = 0.004). Antigen persistence with a fluctuating viral load revealed stable levels of CD38/PD‐1 co‐expression whereas significant rises in viral load were accompanied or even preceded by substantial increases in CD38/PD‐1 co‐expression. The CD38/PD‐1 phenotype clearly distinguishes HIV‐specific CD8 T‐cell responses between controllers and progressors. Whether it plays a causative role in disease progression remains debatable. J. Med. Virol. 82:358–370, 2010.

Stenotrophomonas maltophilia Induced Post-Cataract-Surgery Endophthalmitis: Outbreak Investigation and Clinical Courses of 26 Patients

Background:Stenotrophomonas maltophilia, a microorganism which colonizes plastic material, is a rare causative agent of iatrogenic endophthalmitis.Patients and Methods:A cluster of 26 cases of acute post-cataract-surgery endophthalmitis (PE) was identified. An outbreak investigation was performed. Information was abstracted from patients’ charts and questionnaires sent to patients and their general practitioners. Vision was examined before, during, as well as one and six months after acute PE. Bacterial isolates were subjected to molecular typing.Results:All patients initially received empiric systemic antibiotic treatment. The source of the infections was identified to be the rinsing solution used during cataract surgery, which was contaminated with two strains of S. maltophilia. Antibiotic therapy was subsequently changed to trimethoprim/sulfamethoxazol and ciprofloxacin for 30 days, complemented with iv fluocortolone and topical treatment with prednisolone, ciprofloxacin, and chloramphenicol. Twenty-one patients (81%) received pars plana vitrectomy and were additionally treated with intravitreal injections of vancomycin, amikacin and dexamethasone, or imipenem and dexamethasone, respectively. In addition, oxacillin, mezlocillin, and prednisolone were applied subconjunctivally after vitrectomy. Six months after acute infection, a final visual acuity of ≥ 0.2 was achieved by 21/26 patients (80%), a visual acuity of ≥ 0.5 by 14/26 patients (54%). Twenty of 26 patients (77%, 17 of whom had undergone vitrectomy) achieved a higher visual acuity than before surgery. Patients from the vitrectomy group had a median final visual acuity of 0.5 compared to 0.4 in the 5 patients without vitrectomy. There was 1 retinal ablation, 2 intra-retinal bleedings, and relapse of infection in 2/26 patients (8%), with isolation of S. maltophilia in one of the relapsing infection cases.Conclusions:Empiric antibiotic treatment of PE may not adequately treat rare pathogens such as S. maltophilia. Administration of an effective systemic or intravitreal antibiotic treatment after identification of S. maltophilia may have contributed to the favorable clinical course and relatively low relapse frequency in our patients. Despite the known problem of persistence of S. maltophilia, visual acuity outcome after treatment is comparable to PE induced by other Gram-positive or Gram-negative bacteria.

Prevalence and risk factors of nasal colonization with Staphylococcus aureus - association with HIV infection in older patients.

Nasal S. aureus colonization was detected in 62/127 patients (49%) at a German infectious diseases clinic; MRSA colonization was infrequent at 2.4%. Male gender (OR=2.71, p=0.04), antimicrobial therapy in hospitalized patients (OR=20.1, p=0.02), and HIV infection in patients>42 y of age (OR=7.74, p=0.02) were independent risk factors for S. aureus colonization.

Calcineurin inhibitor dose‐finding before kidney transplantation in HIV patients

Kidney transplantation in HIV‐infected patients is associated with a higher rate of graft rejection as well as an increased toxicity of the immunosuppressive therapy. Specifically, the use of the calcineurin inhibitor tacrolimus is problematic because of a narrow therapeutic range, a high interindividual variability of trough levels, and multiple interactions with combination antiretroviral therapy (cART). Our objective was to establish the optimal individual immunosuppressive dose for the time after kidney transplantation. We administered a temporary course of immunosuppressive therapy in three HIV‐infected patients with end‐stage renal disease (ESRD) after wait‐listing and prior to transplantation for deceased donor kidney transplantation. Starting with a tacrolimus dose of 1 mg twice daily, the dose was titrated to reach a tacrolimus trough level of 8–12 ng/ml. HIV had been diagnosed 7–14 years prior. All patients had no detectable HIV‐1 RNA while on cART. All three patients had been on chronic dialysis for 4, 7, and 10 years. In two patients, the intended tacrolimus trough levels of 8–12 ng/ml were achieved within a month. The required tacrolimus dose ranged from 0.5 mg thrice weekly to 10 mg daily. In one case, ventricular tachycardia occurred, so the immunosuppressive therapy was switched to cyclosporine A. So far, two patients have been transplanted successfully. In summary, dose‐finding of immunosuppressive therapy with tacrolimus in patients on cART before renal transplantation is feasible and appears useful to minimize immunosuppressive therapy‐related complications in the post‐transplantation period.

MRSA – Hygiene-Management, Diagnostik und Therapie

Methicillin-resistant Staphyococcus aureus strains remain a challenge to both patient care and infection control efforts. In addition to the defining resistance to beta-lactams several other antibiotic classes may be ineffective. Some resistance phenotypes exhibit a characteristic distribution pattern between healthcare-associated, community-associated, and livestock-associated MRSA strains. For patients with defined risk factors a search-, destroy-, follow-up-strategy is recommended in order to identify and eliminate MRSA colonization. Mupirocin nasal ointment and extensive hygiene measures are the mainstays of decolonization efforts. Besides vancomycin several other antimicrobials such as rifampin, trimethoprim-sulfamethoxazol, clindamycin, linezolid, and daptomycin are used to treat specific MRSA infections.

Triple worm infestation in an HIV-infected patient

A 32-year-old female African patient presented to the emergency department for abdominal pain. She had been diagnosed with HIV infection 3 years earlier. She was ART-naive with a CD4-T cell count of 456/ll and a viral load of 626 cp/ml. Her C-reactive protein level was elevated at 84.3 mg/l, and no other laboratory abnormality was noted. Surgery for suspected appendicitis was performed. Histopathological work-up revealed phlegmonous appendicitis with localized eosinophilic infiltration and necrotic epitheloid granulomas (Fig. 1a, b). Differential diagnoses included eosinophilic gastroenteritis, hematologic malignancy, and mycobacterial infection. Finally, three species of intestinal worms, Schistosoma mansoni (Fig. 1c), Strongyloides stercoralis (Fig. 1d), and Dicrocoelium dendriticum (Fig. 1e) were detected in a stool sample. Antihelminthic treatment with praziquantel (1,800 mg on days 1 and 8) and albendazole (800 mg qd on days 1–3 and 8–10) was administered. Further stool samples were negative, and the patient remained asymptomatic. The CD4-Tcell counts measured 1 and 4 months later were somewhat higher at 675 and 633/ll, respectively. More than two billion individuals are estimated to be infected with one or more helminth species [1, 2] and over 22 million are HIV-coinfected [3, 4], especially in sub-Saharan Africa. Typical clinical signs and symptoms or laboratory abnormalities are often absent, despite the frequency of typical histopathologic alterations such as eosinophilic granulomas in chronic schistosomiasis [5]. Helminthic infections are not considered to be opportunistic infections. However, helminth-induced immunomodulation may affect the CD4 count [3–6]. The benefit of deworming in helminth/HIV-coinfection is suggested by several studies, but its effect may vary by individual helminth species [4]. Routine screening for tropical parasites according to travel or origin is recommended by current HIV treatment guidelines [7], reflecting the traveland migration-related increasing overlap of tropical medicine and HIV care also in developed countries [8]. S. Sammet M. Huber U. Seybold (&) Sektion Klinische Infektiologie, Medizinische Klinik und Poliklinik IV, Klinikum der Universitat, Ludwig-Maximilians-Universitat Munchen, Pettenkoferstr. 8a, 80336 Munchen, Germany e-mail: useybold@med.uni-muenchen.de

Auch das Herz ist gefährdet

Herz-Kreislauf-Erkrankungen sind inzwischen die dritthäufigste Todesursache bei über 60-jährigen HIV-Patienten. Deshalb ist bei allen HIV-Patienten ein besonderes Augenmerk auf kardiovaskuläre Risikofaktoren zu legen.

[Long-term efficacy of second-line treatment of HIV infection after class change following virological failure on protease inhibitor-based therapy].

BACKGROUND AND OBJECTIVE While there are evidence-based recommendations for the initial combination antiretroviral treatment (cART) of HIV infection, there are no comparative studies on long-term efficacy of different second-line strategies after initial virological failure. The aim of this study was to compare different second-line strategies after virological failure of an initial protease inhibitor (PI) based regimen, specifically the comparison between change to a different PI and class change to a non-nucleoside reverse transcriptase inhibitor (NNRTI). PATIENTS AND METHODS This cohort study retrospectively analyzed patient data documented for the Clinical Surveillance of HIV Disease project (ClinSurv) between 1999 and 2008, run by the Robert Koch Institute in Berlin, Germany. Follow-up data for at least three months of a treatment switch after virological failure of the first-line regimen were available for 157 patients out of the 14,377 patients in the ClinSurv cohort. Eighty-four (54%) of these had a PI-based first-line regimen and were therefore included into the analysis. Fifty-one (61%) of the 84 patients were switched to a different PI (group 1), 33 (39%) to a NNRTI (group 2). Primary end points were the probability of virological failure of the second-line regimen, the duration of a successful second-line regimen and the time to suppression of viral load below the level of detectability. RESULTS There was no significant difference in the median time to virological suppression with 88 days in group 1 and 57 days in group 2 (p = 0.16). After > 3,000 days more than 50% of patients in group 2 (class switch to NNRTI) were still on an effective regimen, their risk of virologic failure thus was significantly lower than in group 1 (switch to a different PI), where the median duration of second-line therapy was only 581 days. Multivariate Cox regression analysis did not identify any of the available covariates as significant predictors of duration of the second-line treatment or as confounders. For group 1, with patients switching within the PI class, there was a more than two-fold risk of virological failure during the time of observation (HR = 2.3; 95%CI 1.1 - 4.9; p = 0.03). CONCLUSION Class switch to a NNRTI as opposed to changing to a different PI following virological failure of a PI-based first-line regimen is associated with significantly better durability of the second-line regimen.

A multicenter study on optimizing piperacillin-tazobactam use: lessons on why interventions fail.

We examined interventions to optimize piperacillin-tazobactam use at 4 hospitals. Interventions for rotating house staff did not affect use. We could target empiric therapy in only 35% of cases. Because prescribing practices seemed to be institution specific, interventions should address attitudes of local prescribers. Interventions should target empiric therapy and ordering of appropriate cultures.