the missing link - recurrent lymph node enlargement and abscesses in an hiv negative female...

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Initial presentation can be with cellulitis, often at the site of minor trauma Aggressive, toxin mediated infections caused by PVL+ MSSA in young, previously well people. Critical care support may be required, and death has occurred following this infection. METHOD n/a RESULTS n/a CONCLUSIONS The HPA has recently issued guidance on ‘‘The diagnosis and management of PVL-associated Staphylococcus aureus (PVL-SA) in England’’. The epidemiology and treatment of PVL-SA infections will be briefly discussed. 0032 HAS THE INTRODUCTION OF SPUTUM INDUCTION IMPROVED THE DIAGNOSIS OF TUBERCULOSIS AND DECREASED THE LENGTH OF HOSPITAL STAY? Kate WOODS, Lucy LAMB, Katherine TAYLOR and Robert DAVIDSON Northwick Park Hospital, London, United Kingdom Background. We previously showed that Sputum Induction (IS) is more sensitive than gastric washings for the diagnosis of pulmonary tuberculosis and this is not enhanced by the use of bronchoalveolar lavage.[1] IS samples are obtained quickly and easily allowing for shorter, less invasive hospital admissions. We wished to evaluate whether routine use of IS (outside of a study situation) improves microbiological diagnosis of tuberculosis, shortens hospital inpatient stay and reduces costs. Methods. We combined clinical and microbiological data from London TB Register (LTBR), hospital databases and case notes to identify all TB patients treated in our unit 6 months prior to and 6 months after introduction of IS sampling at Northwick Park Hospital. Results. After exclusions, we compared 113 TB patients ‘‘pre’’ and 124 patients ‘‘post-IS’’. There was a higher proportion of culture- confirmed cases (62.7% vs. 70.2% [NS]) ‘‘post-IS’’. Introduction of IS led to a reduction in number of patients admitted (p < 0.0001) and length of stay (p < 0.0001), yielding an estimated cost saving of at least £123 per patient. Conclusions. Our routine use of IS for TB diagnosis has led to significantly fewer patients being admitted, a significantly reduced length of stay and reduction in costs. There was improved microbiological diagnosis of TB post introduction of IS but this did not reach statistical significance. [1] Michael Brown, Hansa Varia, Paul Bassett et al. Prospective Study of Sputum Induction, Gastric Washing, and Bronchoalveolar Lavage for the Diagnosis of Pulmonary Tuberculosis in Patients who are unable to expectorate. CID 2007;44: 1415-20. METHOD Patient Population. All TB patients notified at Northwick Park Hospital (NPH) to the LTBR ‘‘pre’’ (1 January 2004 to 1 August 2004) and ‘‘post’’ (1 January 2007 to 1 August 2007) introduction of routine use of induced sputum. Study Design. Retrospective cohort study. Data was collected from LTBR, hospital databases, and case notes. Exclusions. < 16 years old; not under the care of the ID Physicians; initial investigation and treatment started at another Hospital; data unsuitable for analysis. Specimens. TB smear/culture from any specimen taken before, or within 5 days of, starting treatment. Statistical analysis. StatsDirect software. RESULTS Study profile. Patients: 130 ‘‘pre-IS’’, 148 ‘‘post-IS’’. Data analysed, after exclusions, from 113 and 124 patients respectively. Median ages 30 and 34 (p ¼ 0.0456). Predominantly Asian and HIV negative. Culture results. Pulmonary TB (PTB) represented 56.7% ‘‘pre-IS’’ and 42.7% ‘‘post-IS’’ (p < 0.05). Proportion of culture confirmed cases was higher in the ‘‘post-IS’’ group (62.7% vs. 70.2%) but not statistically significant. This was also true for sputa samples of PTB cases (61.2% vs. 65.3%, NS). Length of stay. Less patients admitted ‘‘post-IS’’ (72.6% vs. 37.9%; p < 0.0001) with reduced length of stay (median 2 vs. 0 days; p < 0.0001). Estimated cost saving: £123.41/ patient. CONCLUSIONS The routine introduction of induced sputum (IS) for TB diagnosis at NPH has resulted in significantly less patients being admitted for investigation of TB. The use of IS has also significantly shortened length of stay for TB patients, with a corresponding reduction in costs, conferring benefits not only on the patient but also for the NHS. Our sample was too small to show a significant change in proportion of culture confirmed TB cases, despite sending more sputum samples. Of note, the Mycobacterium TB resistance pattern within our population did not significantly change from 2004 to 2007. 0033 THE MISSING LINK - RECURRENT LYMPH NODE ENLARGEMENT AND ABSCESSES IN AN HIV NEGATIVE FEMALE RECEIVING CHEMOTHERAPY FOR FULLY SENSITIVE MYCOBACTERIUM TUBERCULOSIS Meghan PERRY 1 , Federica FAGGIAN 1 , Clifford LEEN 1 , Rainer DOFFINGER 2 and Dinakantha KUMARARATNE 2 1 Regional Infectious Diseases Unit, Western General Hospital, Edinburgh, United Kingdom, 2 Department of Immunology, Addenbrookes Hospital, Cambridge, United Kingdom S440

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S440

Initial presentation can be with cellulitis, often at the site of minortraumaAggressive, toxin mediated infections caused by PVL+ MSSA in young,previously well people. Critical care support may be required, anddeath has occurred following this infection.

METHOD

n/a

RESULTS

n/a

CONCLUSIONS

The HPA has recently issued guidance on ‘‘The diagnosis andmanagement of PVL-associated Staphylococcus aureus (PVL-SA) inEngland’’. The epidemiology and treatment of PVL-SA infections willbe briefly discussed.

0032

HAS THE INTRODUCTION OF SPUTUM INDUCTION IMPROVED THE DIAGNOSIS OF TUBERCULOSIS AND DECREASED THELENGTH OF HOSPITAL STAY?

Kate WOODS, Lucy LAMB, Katherine TAYLOR and Robert DAVIDSONNorthwick Park Hospital, London, United Kingdom

Background. We previously showed that Sputum Induction (IS) ismore sensitive than gastric washings for the diagnosis of pulmonarytuberculosis and this is not enhanced by the use of bronchoalveolarlavage.[1] IS samples are obtained quickly and easily allowing forshorter, less invasive hospital admissions. We wished to evaluatewhether routine use of IS (outside of a study situation) improvesmicrobiological diagnosis of tuberculosis, shortens hospital inpatientstay and reduces costs.Methods. We combined clinical and microbiological data fromLondon TB Register (LTBR), hospital databases and case notes toidentify all TB patients treated in our unit 6 months prior to and 6months after introduction of IS sampling at Northwick Park Hospital.Results. After exclusions, we compared 113 TB patients ‘‘pre’’ and124 patients ‘‘post-IS’’. There was a higher proportion of culture-confirmed cases (62.7% vs. 70.2% [NS]) ‘‘post-IS’’. Introduction of ISled to a reduction in number of patients admitted (p< 0.0001) andlength of stay (p< 0.0001), yielding an estimated cost saving of atleast £123 per patient.Conclusions. Our routine use of IS for TB diagnosis has led tosignificantly fewer patients being admitted, a significantly reducedlength of stay and reduction in costs. There was improvedmicrobiological diagnosis of TB post introduction of IS but this did notreach statistical significance.[1] Michael Brown, Hansa Varia, Paul Bassett et al. Prospective Studyof Sputum Induction, Gastric Washing, and Bronchoalveolar Lavagefor the Diagnosis of Pulmonary Tuberculosis in Patients who areunable to expectorate. CID 2007;44: 1415-20.

METHOD

Patient Population. All TB patients notified at Northwick ParkHospital (NPH) to the LTBR ‘‘pre’’ (1 January 2004 to 1 August 2004)and ‘‘post’’ (1 January 2007 to 1 August 2007) introduction of routineuse of induced sputum.

Study Design. Retrospective cohort study. Data was collected fromLTBR, hospital databases, and case notes.Exclusions.< 16 years old; not under the care of the ID Physicians;initial investigation and treatment started at another Hospital; dataunsuitable for analysis.Specimens. TB smear/culture from any specimen taken before, orwithin 5 days of, starting treatment.Statistical analysis. StatsDirect software.

RESULTS

Study profile. Patients: 130 ‘‘pre-IS’’, 148 ‘‘post-IS’’. Data analysed,after exclusions, from 113 and 124 patients respectively. Medianages 30 and 34 (p¼ 0.0456). Predominantly Asian and HIV negative.Culture results. Pulmonary TB (PTB) represented 56.7% ‘‘pre-IS’’and 42.7% ‘‘post-IS’’ (p< 0.05). Proportion of culture confirmedcases was higher in the ‘‘post-IS’’ group (62.7% vs. 70.2%) but notstatistically significant. This was also true for sputa samples of PTBcases (61.2% vs. 65.3%, NS).Length of stay. Less patients admitted ‘‘post-IS’’ (72.6% vs. 37.9%;p< 0.0001) with reduced length of stay (median 2 vs. 0 days;p< 0.0001). Estimated cost saving: £123.41/ patient.

CONCLUSIONS

The routine introduction of induced sputum (IS) for TB diagnosis atNPH has resulted in significantly less patients being admitted forinvestigation of TB. The use of IS has also significantly shortenedlength of stay for TB patients, with a corresponding reduction incosts, conferring benefits not only on the patient but also for theNHS. Our sample was too small to show a significant change inproportion of culture confirmed TB cases, despite sending moresputum samples. Of note, the Mycobacterium TB resistance patternwithin our population did not significantly change from 2004 to 2007.

0033

THE MISSING LINK - RECURRENT LYMPH NODE ENLARGEMENT AND ABSCESSES IN AN HIV NEGATIVE FEMALE RECEIVINGCHEMOTHERAPY FOR FULLY SENSITIVE MYCOBACTERIUM TUBERCULOSIS

Meghan PERRY1, Federica FAGGIAN1, Clifford LEEN1, Rainer DOFFINGER2 and Dinakantha KUMARARATNE2

1Regional Infectious Diseases Unit, Western General Hospital, Edinburgh, United Kingdom, 2Department of Immunology, AddenbrookesHospital, Cambridge, United Kingdom

S441

We present of a case of non-resolving MycobacteriumTuberculosis infection in an HIV negative female with nosignificant past medical history. Following a non-specific febrilepresentation investigations revealed thoracic lymphadenopathyand fully sensitive Mycobacterium Tuberculosis was grown frombronchoalveolar lavage. She did not improve with quadrupletherapy and despite the transient addition of steroids and theextension of her therapy to include Clarithromycin andMoxifloxacin she continued to develop lymph node enlargementand abscesses at multiple sites that were AFB positive onmicroscopy but culture negative. Immunological tests wereperformed following a year of treatment to assess her TH1response; cytokine quantification following whole bloodstimulation showed markedly reduced interferon gammaproduction. There were no other significant immunologicalabnormalities. As there was no clinical improvement onconventional therapy she received subcutaneous interferon-gamma three times a week at 50 mg per metre squared for threemonths. There was complete healing of all her lesions, resolutionof her clinical symptoms and no demonstratable adverse effects.She received one year of TB therapy from the day ofcommencement of the interferon-gamma replacement. Follow-up immunological testing 4 months after the interferonreplacement stopped revealed normal interferon-gammaproduction. However repeat testing following termination oftreatment again demonstrated reduced interferon production.This case demonstrates the need for through consideration ofhost-pathogen interactions in managing complicatedTuberculosis. It also suggests that screening the IFN-gamma/IL12axis of patients without HIV, with disseminated or progressivetuberculosis despite a fully sensitive organism, should beconsidered, as it may allow initiation of appropriate life savingtreatment.

METHOD

A 26 year old Indian female physiotherapist, resident in the UK fortwo and a half years, presented with a 4 week history of headache,myalgia, fever and night sweats. She had no significant past medicalhistory. On examination she was pyrexial with no clinical

lymphadenopathy. Initial investigations revealed a CXR witha prominent right hilum, CRP 46, ESR 69, negative HIV serology anda normal lumbar puncture. CT chest (IMAGE -CT)confirmed hilar,paratracheal and subcarinal lymph nodes and fully sensitiveMycobacterium Tuberculosis was grown from bronchoalveolar lavageand early morning urine. Standard quadruple therapy wascommenced with initial symptomatic improvement

RESULTS

Over the course of the next year, with documented full adherence,she remained symptomatic with development of recurrent lymphnodes and abscesses in different locations. Aspirates of theseabscesses(IMAGE - PHOTO) remained AFB positive on microscopy butnegative on culture throughout this period and her CRP and ESRremained elevated. Normal immunoglobulin and complement levelswere verified and repeat cytology examination found no evidence ofmalignancy or lymphoma. One year following commencement oftherapy definitive imaging in the form of a CT chest (IMAGE-CT)showed improvement of the initial lesions but new nodalenlargement with appearances suggestive of central caseation.

CONCLUSION

After one month of treatment she was managed with a month of highdose prednisolone for a presumed paradoxical reaction and herquadruple therapy was extended after 7 months to cover for theemergence of resistance.Immunological tests were performed revealed markedly reducedinterferon-g production. She received subcutaneous interferon-g forthree months and a further year of Tuberculosis therapy. There wascomplete healing of all her lesions and resolution of her clinicalsymptoms. Follow-up immunological testing revealed normalinterferon-g production 4 months after the interferon therapy hadstopped but repeat testing after termination of treatmentdemonstrated decreased interferon production. This casedemonstrates the need for thorough consideration of host pathogeninteractions and stresses the importance of the IFN-gamma/IL12pathway.

0034

THE MISSING LINK - RECURRENT LYMPH NODE ENLARGEMENT AND ABSCESSES IN AN HIV NEGATIVE FEMALE RECEIVINGCHEMOTHERAPY FOR FULLY SENSITIVE MYCOBACTERIUM TUBERCULOSIS. COVERING LETTER

Meghan PERRY1, Federica FAGGIAN1, Clifford LEEN1, Rainer DOFFINGER2 and Dinakantha KUMARARATNE2

1Regional Infectious Disease Unit, Western General Hospital, Edinburgh, United Kingdom, 2Department of Immunology, AddenbrookesHospital, Cambridge, United Kingdom

Covering letter.We present of a case of non-resolving Mycobacterium Tuberculosisinfection in an HIV negative female with no significant past medicalhistory. Following a non-specific febrile presentation investigationsrevealed thoracic lymphadenopathy and fully sensitiveMycobacterium Tuberculosis was grown from bronchoalveolar lavage.She did not improve with quadruple therapy and despite the transientaddition of steroids and the extension of her therapy to includeClarithromycin and Moxifloxacin she continued to develop lymph nodeenlargement and abscesses that were AFB positive on microscopy butculture negative. Immunological tests were performed followinga year of treatment to assess her TH1 response and cytokinequantification following whole blood stimulation showed markedlyreduced interferon gammaproduction. Therewere noother significant

immunological abnormalities. As there was no clinical improvement onconventional therapy she received subcutaneous interferon-gammathree times a week at 50 mg per metre squared for three months. Therewas complete healing of all her lesions, resolution of her clinicalsymptoms and no demonstratable adverse effects. She received oneyear of TB therapy from the day of commencement of the interferon-gamma replacement. Follow-up immunological testing at this pointrevealed normal interferon-gamma production. This casedemonstrates the need for thorough consideration of pathogen - hostinteractions in managing complicated Tuberculosis. It also suggeststhat screening the IFN-gamma/IL12 axis of patients without HIV withdisseminated or progressive tuberculosis despite a fully sensitiveorganism should be considered, as it may allow initiation ofappropriate life saving treatment.