Vancomycin-Intermediate Staphylococcus aureus (VISA) is stillÂ uncommon among MRSA isolates. In our region, we rarely encountera case of VISA and/or GISA bacteremia. Here, we report a man whoÂ suffered from autoimmune hepatitis on immunosuppressive therapyÂ and thoracic transverse myelitis suspected to be due to polyomavirusÂ infection; he developed persistent MRSA blood stream infection,Â PVL-positive and MLST clonal complex 88 which is reported mostÂ commonly from Africa. A strain with Vancomycin susceptibility ofÂ 4 â€“ 6 Âµg/ml (VISA) was initially identifid, retested again elsewhereÂ and showed MIC of 2Âµg/ml and Teicoplanin susceptibility of 4Âµg/ml.Â Treatment failure occurred while attaining higher serum vancomycinÂ levels than recommended and died

Abu Shanab, Lamya

Fattah Yacoub, Abdel

Wadi Al Ramahi, Jamal Ahmad

International Medical Publisher Journals (iMedPub)

The InTernaTIonal arabIc Journal of anTImIcrobIal agenTs    Issn 2174-9094© Under License of Creative Commons Attribution 3.0 License 12015Vol. 5 No. 2:2 doi: 10.3823/769iMedPub Journalshttp://journals.imed.pubThis article is available from: www.iajaa.org   /   www.medbrary.comA Patient with autoimmune hepatitis and transverse myelitis presented with persistent Staphylococcus aureus bacteremia, the discrepancies in assessing susceptibility; VISA versus Non-VISA1   Internal Medicine, Jordan Hospital.2   Pharmacy Department, Jordan Hospital, Amman, JordanCorresponding author:Jamal Wadi Al Ramahi MD, FIDSA jamalwadimd@yahoo.comJamal Wadi Al Ramahi1 Abdel Fattah Yacoub1, Lamya Abu Shanab2AbstractVancomycin-Intermediate Staphylococcus aureus (VISA) is still uncommon among MRSA isolates. In our region, we rarely encounter a case of VISA and/or GISA bacteremia. Here, we report a man who suffered from autoimmune hepatitis on immunosuppressive therapy and thoracic transverse myelitis suspected to be due to polyomavirus infection; he developed persistent MRSA blood stream infection, PVL-positive and MLST clonal complex 88 which is reported most commonly from Africa. A strain with Vancomycin susceptibility of 4 – 6 µg/ml (VISA) was initially identified, retested again elsewhere and showed MIC of 2µg/ml and Teicoplanin susceptibility of 4µg/ml. Treatment failure occurred while attaining higher serum vancomycin levels than recommended and died. Keywords: Vancomycin-intermediate S. aureus, VISA, S. aureus, Panton-Valentine-Leukocidin. Antimicrobial susceptibility testing The InTernaTIonal arabIc Journal of anTImIcrobIal agenTsIssn 2174-90942015Vol. 5 No. 2:2 doi: 10.3823/7692  This article is available from: www.iajaa.org   /   www.medbrary.com IntroductionSoon after the initial cases of Vancomycin-Inter-mediate Staphylococcus aureus (VISA) were report-ed form Japan in1997, it relentlessly seems to be reported worldwide, predisposing for more vanco-mycin resistant strains i.e. VRSA, though it is still a rare sporadic isolate. However, VISA strains, a more frequent isolates compromise glycopeptides activity and complicate the treatment regimens of patients infected with these strains [1].In an international study, hVISA phenotype (defined as the presence of subpopulations typically at a rate of 1 organism per 105–106 of MRSA with VISA) occurred in more than one-quarter of MRSA blood isolates from pa-tients with infective endocarditis, though it varied in frequency by geographic region [2, 3].In Taiwan, isolates from ten centers collected 1000 MRSA, the prevalence of VISA isolates were 0.2% and hVISA isolates 0.7% [4].In our region, reports from the Arab Countries have been published; In Jordan a case of VISA (MIC = 4 mg/dl) was reported in the year 2006 by F. Bakri and coworkers in a patient with erythroder-mic psoriasis who suffered three months persistent Staphylococcus aureus bacteremia [5]. MRSA strains with decreased susceptibility for vancomycin were reported from Qassim region in Saudi Arabia [6]. VISA, hVISA persistent blood stream infection in spite of high blood vancomycin levels were report-ed from Saudi Arabia as well [7]. Another interest-ing report came from Oman on the treatment of infective endocarditis due to VISA; a patient was treated with a combination of intravenous linezolid and fusidic acid without a need for surgical inter-vention and resulted in complete cure [8]. Moreover, a report on glycopeptide-intermediate Staphylococ-cus aureus (GISA) were reported form north Leba-non, five strains out of 113 (4.4%) were resistant to teicoplanin (GISA) by MIC dilution method and no strain was resistant to vancomycin. Although all MRSA isolates were reported as susceptible by Muller-Hinton agar diffusion method [9], we should consider other methods for testing MRSA for MIC when it is needed. Here, we present a patient who was immuno-suppressed and had had suffered from persistent Staphylococcus aureus blood stream infection in spite of being on unintentional high serum levels of vancomycin. The isolate show discrepant susceptibil-ity testing between different laboratories, once was interpreted as VISA, at another institution was not.Case ReportA 47 year old male patient from Yemen with type 2 diabetes mellitus on insulin, and autoimmune hepatitis since 1996 on Immunosuppressive therapy; dexamethasone 4 mg/day and azathioprine 50 mg twice daily. He was admitted on November 1, 2014 in Jordan hospital complaining of bilateral lower limb weakness of one month duration,it was sudden in onset and progressive, it was noticed when lifting heavy objects, and later falling down spontaneously on walking. Dorsal spine MRI imaging showed le-sion in the anterior part of dorsal spine (Figure 1). Differential diagnosis included viral transverse myeli-Figure 1. A lesion in the anterior part of the spinal cord opposing the lower part of T5 to the lower part of the T6 vertebral bodies,it shows no significant enhancement in post contrast images.The InTernaTIonal arabIc Journal of anTImIcrobIal agenTsIssn 2174-90942015Vol. 5 No. 2:2 doi: 10.3823/769© Under License of Creative Commons Attribution 3.0 License 3tis, demyelination, and low grade neoplasm.He was transferred from another hospital with decrease level of consciousness; he was admit-ted to the ICU, and on admission he was sleepy, generally week and could not move his legs. CSF analysis showed WBC = 44/mm3, RBC =100 /mm3, Protein=308 mg/dl, Glucose =148 mg/dl, he was started on ceftriaxone 2gm/12 hours and vancomy-cin 1gm/12 hours. Dorsal MRI showed a lesion of the anterior part of the spinal cord ,extending op-posite the lower part of D5 to the lower part of the D6 vertebral bodies, it show no significant enhance-ment in the post contrast images (Figure 1). Dexa-methasone was discontinued on November 3rd and methylprednisolone 1gm/24hours was started. On November 6th he started fever (38.60C orally) when an infectious diseases consultation was sought. Lab-oratory tests for Clostridium difficile toxins, CMV IgM, toxoplasma IgM, urine legionella antigen, my-coplasma IgM, and Chlamydophila pneumoniae IgM, HIV antibodies, HCV Antibodies and HBsAg were all negative. Urine sediment for decoy cells was positive, and BK-Polyomavius by Taq-Man real time PCR (Anatolia GeneworkInc, Istanbul, Turkey) was positive. Immunosuppressive therapy was ad-vised to be tapered and ceftriaxone and vancomycin were discontinued as aerobic blood cultures twice showed no growth with abating fever. Few days later he redeveloped fever, and blood culture grew Enterobacter cloacae, he was started on pipracillin/tazobactam 4.5 gm/8hours, fever subsided for sev-eral days and the patient was relatively stable with his baseline neuro-deficit. A repeat dorsal spine MRI showed no significant changes from previous imag-ing and no evidence of new lesions.About a week later, the patient developed high fever (38.4 0C), and his blood cultures grew methi-cillin-resistant Staphylococcus aureus (MRSA), van-comycin 2gm IV loading followed by 1gm/12hours was started, 2D- echocardiogram was normal, and bone scan was reported as multiple abnormal areas of increased radiotracer uptake seen at both sterno-clavicular joints, both knee joints, and irregular tracer uptake is seen at D5-D6 and D12 vertebral bodies. Five days into vancomycin treatment; on November 19th fever persisted, and empiric fluconazole 600mg IV loading then 400mg IV/24hours was added, van-comycin trough levels were monitored aiming to keep levels 15 - 20 µg/ml, althoughin most instances levels were unintentionally elevated due to meas-ured deterioration in renal function (Figure 3). The patient did not have clinical response, vancomycin E-test (bioMérieux Marcy l’Etoile. 376, chemin de l’Orme 69280 Marcy l’Etoile) was done and initially showed complete resistance (CLSI MIC > 16 µg/ml), an immediate repeat of the E-test resulted in van-comycin-intermediate Staphylococcus aureus (VISA) MIC = 4 – 6 µg/ml (CLSI MIC for VISA equals 4 – 8 µg/ml) (Figure 2). Linezolid 600 mg IV/12hours and imipenem/cilastatin 250 mg/6 hours were started; the later and fluconazole were discontinued as re-peat blood cultures showed the same S. aureus isolate. The patient showed continuous clinical de-Figure 2. Muller-Hinton growth media with MRSA growth and E-test strip showing clear zone 4 – 6 µg/ml.The InTernaTIonal arabIc Journal of anTImIcrobIal agenTsIssn 2174-90942015Vol. 5 No. 2:2 doi: 10.3823/7694  This article is available from: www.iajaa.org   /   www.medbrary.com terioration, white lungs on chest radiogram, poor arterial blood gases, electrolytes imbalance, further renal function deterioration, intractable shock and met his demise.MIC and Molecular analysisDue to E-testing discrepancy at our laboratory, a preserved Staphylococcus aureus isolate was retest-ed for susceptibility by the (Antimicrobial Resistance and Healthcare-Associated Infections Reference Unit. Public Health England, 61 Colindale Avenue, London NW9 5EQ, Reference number PHE ref. No.: H1 5020 1048), and showed that vancomycin MIC was 2 µg/ml (CLSI vancomycin susceptible ≤ 2), while teicoplanin MIC was 4 µg/ml (CLSI suscepti-ble ≤ 8). Staphylococcus aureus typing revealed spa type: t690, (repeat succession: 07-12-21-17-13-13-34-34-34-33-34) and Panton-Valentine-Leukocidin (Luk-PV) positive strain.DiscussionIn our region, we rarely document patients with MRSA-induced sepsis with elevated or creeping MIC phenomena, and persistent bacteremia while on vancomycin treatment, due to resources limi-tations. A case was presented by my group (Rula Rashed MD, Fadi Shaqlous PharmD) earlier in2010, in a regional meeting; the isolate demonstrated creeping vancomycin MIC [10] while the patient was on treatment with therapeutic vancomycin lev-els, MIC creped in a month time from 0.125 µg/ml, to 0.75 µg/ml, to 1.5 µg/ml as was verified by E-test. The patient continued to have pus discharge from a traumatized combat-related infected foot wound with repeated surgical debridement, till he was switched to linezolid with almost brisk response and discharged home (unpublished report).Our current patient was immunocompromised, and had thoracic spinal cord transverse myelitis that was suspected to be due polyomavirus infection, which may have been predisposed by immunosup-pressive therapy. Again he showed lack of response to vancomycin therapy, though the strain was with-in the susceptibility range, and vancomycin serum levels were much higher than what was desired (Figure 3). Failure of vancomycin therapy for VISA strains is well described, as the target attainment (AUC/MIC ≥ 400) cannot be reached [11]. Higher failure rates were also reported with “creped” van-comycin MIC, though still within susceptibility rang-es of ≤ 2 µg/ml; the upper CLSI limit for vancomycin susceptibility [12, 13]. Our S. aureus isolate as re-tested in (Antimicrobial Resistance and Healthcare-Associated Infections Reference Unit. Public Health England, 61 Colindale Avenue, London NW9 5EQ), it exhibited vancomycin susceptibility and did not meet CLSI MIC level for GISA [12,14].The isolate belongs to spa type that has been associated with PVL-MRSA and belonging to MLST clonal complex 88 reported most commonly from Africa. This mecA positive S. aureus encodes Pantone-Valentine leuco-cidin (PVL) genes. Infection with PVL-SA most com-monly presents as primary cutaneous lesions [15, 16]. However PVL-positive S. aureus was reported to be associated with serious life threatening disease, namely community-associated pneumonia (CAP) in four patients, all did not have the classical risk fac-tors for infection with strains carrying PVL genes [17].The patient was started on Linezolid but the duration of therapy was not enough to appreciate a response, and he died.In our case, a lesson to be learned; laboratories should pay attention for microorganisms’ antimicro-bial susceptibility testing, taking into account the imported tests kits source, storage and quality; here the E-tests strips that showed discrepant MIC val-ues for .S aureus in the same laboratory and tests strips brand, though labeled as not expired; E-test (bioMérieux Marcy l’Etoile. 376, chemin de l’Orme 69280 Marcy l’Etoile).The InTernaTIonal arabIc Journal of anTImIcrobIal agenTsIssn 2174-90942015Vol. 5 No. 2:2 doi: 10.3823/769© Under License of Creative Commons Attribution 3.0 License 5Another lesson learned from this case, that a persistent fever in -compromised patients is a risk factor for the development of more antibiotic resist-ant patterns of S. aureus infections and moreover in PVL-positive strains. This study also suggests the early implementation of antibiotic treatment based on suspicion of the frank pathogen, in order to cover strains with higher MICs, before the actual MIC is available [18].AcknowledgementWe thank Professor David Livermore for his co-operation, and we thank Doctor Robert Hill for his assistance (Head of Antibiotic Susceptibility. Anti-microbial Resistance and Healthcare-Associated In-fections Reference Unit. Public Health England, 61 Colindale Avenue, London NW9 5EQ)References 1. Hiramatsu K, Aritaka N, Hanaki H, Kawasaki S, Hosoda Y, et al. Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet. 1997;350(9092):1670-3 2. In-GyuBae, Jerome J. Federspiel, Jose´ M. Miro ,´ Christopher W. Woods, Vance G. Fowler Jr et al. Heterogeneous Vancomycin-Intermediate Susceptibility Phenotype in Bloodstream Methicillin-Resistant Staphylococcus aureus Isolates from an International Cohort of Patients with Infective Endocarditis: Prevalence, Genotype, and Clinical Significance. Jour Infect Dis 2009; 200:1355–66 3. Tenover FC, Moellering RC Jr. The rationale for revising the Clinical and Laboratory Standards Institute vancomycin minimal inhibitory concentration interpretive criteria for Staphylococcus aureus. Clin Infect Dis 2007; 44:1208–15 4. Ho CM, Hsueh PR, Liu CY, Lee SY, Chiueh TS, et al. Prevalence and accessory gene regulator (agr) analysis of vancomycin-intermediate Staphylococcus aureus among methicillin-resistant isolates in Taiwan--SMART program, 2003. Eur J ClinMicrobiol Infect Dis 2010;29(4):383-9. doi: 10.1007/s10096-009-0868-4 5. Faris G. Bakri, Nisreen Abu AL-Hommos, AemShehabi, Randa G. Naffa, Longzhu Cui et al. Persistent bacteraemia due to Figure 2. Muller-Hinton growth media with MRSA growth and E-test strip showing clear zone 4 – 6 µg/ml.The InTernaTIonal arabIc Journal of anTImIcrobIal agenTsIssn 2174-90942015Vol. 5 No. 2:2 doi: 10.3823/7696methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in a patient with erythrodermic psoriasis. Scandinavian Journal of Infectious Diseases 2007;39(5):457-460. 6. Abdullateef A. Alzolibani, Ahmad A. Al Robaee, Hani A. Al Shobaili, Jalal A. Bilal, Mohammad Issa Ahmad et al. Documentation of vancomycin-resistant Staphylococcus aureus (VRSA) among children with atopic dermatitis in the Qassim region, Saudi Arabia. ActaDermatovenerologicaAlpina, Pannonica et Adriatica 2012;21:51-53. doi:10.2478/v10162-012-0015-2 7. S. Al-Obeid, Q. Haddad, A. Cherkaoui, J. Schrenzel, and P. Francois. First Detection of an Invasive Staphylococcus aureus Strain (D958) with Reduced Susceptibility to Glycopeptides in Saudi Arabia. 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A Patient with autoimmune hepatitis and transverse myelitis presented with persistent Staphylococcus aureus bacteremia, the discrepancies in assessing susceptibility; VISA versus Non-VISA

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A Patient with autoimmune hepatitis and transverse myelitis presented with persistent Staphylococcus aureus bacteremia, the discrepancies in assessing susceptibility; VISA versus Non-VISA

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