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    SAMJ: South African Medical Journal

    versão On-line ISSN 2078-5135
    versão impressa ISSN 0256-9574

    SAMJ, S. Afr. med. j. vol.108 no.5 Pretoria Mai. 2018

    http://dx.doi.org/10.7196/samj.2018.v108i5.12957 

    IN PRACTICE
    CASE REPORT

     

    Co-infection with Streptococcus pneumoniae and Listeria monocytogenes in an immunocompromised patient

     

     

    C J OppermanI; C BamfordII

    IMB ChB, BSc Hons (Microbiology); Division of Medical Microbiology, National Health Laboratory Service, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
    IIMB ChB, FCPath MMed Pathology(Microbiology) ; Division of Medical Microbiology, National Health Laboratory Service, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa

    Correspondence

     

     


    ABSTRACT

    A 34-year-old HIV-positive man with a history of chronic substance abuse was admitted with dual infection of Streptococcus pneumoniae and Listeria monocytogenes. Combined bacteraemia with S. pneumoniae and L. monocytogenes is very rare. To the best of our knowledge, this is the first such case documented at our institution and in South Africa. Ampicillin should be added to antibiotic regimens to improve patient outcome if L. monocytogenes infection is suspected. Co-infections that occur with L. monocytogenes may have conflicting antibiotic treatment options. This case report emphasises the need for a good relationship between the local microbiology pathologist and physician to select appropriate antibiotic treatment before definitive results are available.


     

     

    In September 2017, the National Institute for Communicable Diseases (NICD) released a statement reporting an unprecedented increase in the number of Listeria cases across South Africa (SA). The increase was noted in the private and public sectors, with 190 confirmed cases of listeriosis across the country between January and August 2017. The NICD also initiated enhanced surveillance at a number of hospitals nationally to gather additional information.[1] An increase in Listeria monocytogenes isolates was detected at our institution. Seven cases were reported at our laboratory in 2016. This figure increased to 14 confirmed listeriosis cases up to October 2017, with 12 of these clustering between June and October (unpublished data -Division of Medical Microbiology, Department of Pathology, Groote Schuur Hospital, Cape Town, SA, 2017). This case report increases awareness about L. monocytogenes and highlights the potential for co-infections.

     

    Case report

    A 34-year-old man presented to a local hospital with a 3-week history of worsening cough and dyspnoea. He had a long-standing history of methamphetamine and cannabis use. The patient was also HIV-positive, with a recent absolute CD4+ count of 32 ceUs/μΕ He was not on antiretroviral therapy and had not been admitted to hospital previously. He required intubation and ventilation because of respiratory distress, and the chest radiograph confirmed a multilobar pneumonia. The patient also required inotropes for septic shock and blood transfusion for severe anaemia (Hb 4.8 g/dL). Laboratory tests showed hypoglycaemia, hypocalcaemia and deranged liver enzymes, with normal kidney function. The patient was treated empirically with ceftriaxone and azithromycin before being transferred to a tertiary hospital intensive care unit.

    Management and investigations

    A blood sample was taken on admission. After 14 hours, a Gram stain showed a combination of Gram-positive cocci in chains and small Gram-positive bacilli. The following day, based on preliminary laboratory results, the presence of Listeria and Streptococcus pneumoniae was suspected. Ampicillin was added to the patient's antibiotic treatment, which had in the interim been escalated to imipenem by the attending clinicians owing to the severity of the illness and apparent concern about Gram-negative infection. The identification of both organisms was subsequently confirmed using routine laboratory methods (Fig. 1), including the Vitek 2 system (bioMérieux, SA). Both organisms were susceptible to penicillin, with minimum inhibitory concentrations (MICs) of <0.06 μg/mL and 0.125 μg/mL for S. pneumoniae and L. monocytogenes, respectively. MIC determinations were done using the Vitek 2 streptococcal antibiotic susceptibility test card (AST-ST01, USA), supported by oxacillin disc testing for S. pneumoniae and Epsilometer testing (E-test) (bioMérieux, SA) for L. monocytogenes (Fig. 2). L. monocytogenes was also cultured from a second blood sample taken on admission,which showed growth after 35 hours. Once antibiotic susceptibility results were available, definitive treatment with ampicillin and co-trimoxazole was initiated and administration of other antibiotics was discontinued. Acute renal failure at the time precluded the use of gentamicin. Meningo-encephalitis was not suspected, as no cells or organisms were present in the cerebrospinal fluid and there was no subsequent growth of bacteria. No pathology was noted on a computed tomography scan of the brain. No additional pathogens were detected and results of laboratory tests for Mycobacterium tuberculosis and Legionella serogroup 1 were negative. An echocardiogram revealed cardiomegaly with signs of biventricular failure, conduction abnormalities and an akinetic septum. An ischaemic hepatic liver injury was suspected. Multiorgan failure followed an acute kidney injury secondary to sepsis, with a metabolic acidosis. A poor response to adequate treatment, decline in clinical presentation, two resuscitating events in the intensive care unit and poor prognosis with multi-organ failure prompted the withdrawal of active treatment. The patient passed away within 7 days of initial admission to hospital.

     

     

     

     

    Discussion

    Dual infection with S. pneumoniae and L. monocytogenes is rare, but not unknown. A retrospective Danish study between 1997 and 2012 reviewed 231 patients with L. monocytogenes bacteraemia and/or meningitis. The investigators documented 4 polymicrobial patients, 2 of whom were co-infected with S. pneumoniae. One patient died after 2 days of definitive treatment with ampicillin in combination with gentamicin. The other patient received benzylpenicillin as monotherapy and survived. The remaining 2 co-infected patients were also infected with Escherichia coli.[2]L. monocytogenes has been documented as a rare concomitant infection in an immunocompetent patient with cryptococcal disease.[3] Interactions between bacteria and viruses are an emerging topic in human infections, with evidence that an indirect interaction between the measles virus and L. mono-cytogenes promotes their co-infection.[4]

    The mortality rate associated with L. monocytogenes is high - ranging from 20% to 30%, even with adequate antibiotic treatment. The variability in mortality can be explained by differences in risk factors, delay in diagnosis and inadequate empirical antibiotic treatment.[2,5] Significant risk factors associated with 30-day mortality in the above-mentioned Danish study included septic shock, altered mental state and inadequate treatment, especially with the cephalosporins[2]The Multicentric Observational NAtional Study on Listeriosis and ListeriA (MONALISA)[6] was a national prospective observational cohort study performed in France between 2009 and 2013. It showed that the most important mortality prognostic factors for both Listeria bacteraemia and neurolisteriosis are multi-organ failure, aggravation of any pre-existing organ dysfunction, ongoing cancer, and monocytopenia.^ It is unfortunate that our patient had multiorgan failure, anaemia, septic shock and an altered mental state, despite being on adequate antibiotic treatment.

    Therapeutic guidelines for the treatment of Listeria lack a strong evidence base, as no clinical trials have been done regarding this disease, which is considered rare. The incidence of listeriosis is estimated at 3 - 6 cases per million population per year in the western hemisphere.[6,7]Listeria is intrinsically resistant to cephalosporins, while ampicillin and benzylpenicillin remain the preferred antibiotics for treatment.[8,9] The addition of a second agent, usually gentamicin, is recommended in cases of meningitis/encephalitis, endocarditis or bacteraemia in immunocompromised hosts.[10,11] Co-trimoxazole is an acceptable alternative, either as monotherapy in patients with anaphylactic reactions to penicillins, or as combination therapy when gentamicin is not tolerated.[12-14

    The diagnosis of Listeria organisms is made by culturing clinical specimens such as blood, cerebrospinal fluid, amniotic fluid, placenta or other sterile body fluids. Ideally, these specimens should be taken before administering antibiotics. In our case, ampicillin was added early, based on the provisional detection of Listeria co-infection. Blood cultures were done before starting antibiotics, and the broad-spectrum antibiotics were subsequently de-escalated to narrowspectrum agents once the organisms had been identified.

     

    Conclusion

    It can be concluded from this case that ampicillin may be added to the antibiotic cover if listeriosis is suspected in a high-risk group. Vulnerable patients include those who are immunocompromised, pregnant women, neonates and the elderly. However, in the setting of the current national listeriosis outbreak, ampicillin should be added to ceftriaxone/ cefotaxime for the empirical treatment of suspected bacterial meningitis in all patients.[15] Challenging empirical antibiotic choices might have to be made regarding co-infections, which require consultation with an infectious diseases specialist or microbiology pathologist. The current case report also highlights the importance of a close relationship between the local microbiologist and physician to select appropriate antibiotic therapy and potentially improve patient outcome.

    Acknowledgement. We thank the family of the deceased patient, who gave permission and their blessing to write this report.

    Author contributions. Both authors contributed equally.

    Funding. None.

    Conflicts of interest. None.

     

    References

    1. National Institute for Communicable Diseases, Division of the National Health Laboratory Service. An unprecedented increase of listeriosis in 2017 in Gauteng Province. Communicable Diseases Communique 2017;16(9):8. http://www.nicd.ac.za/wp-content/uploads/2017/09/NICD-Communicable-Diseases-Communique_September2017_final.pdf (accessed 4 October 2017).         [ Links ]

    2. Thonnings S, Knudsen JD, Sch0nheyder HC, et al. Antibiotic treatment and mortality in patients with Listeria monocytogenes meningitis or bacteraemia. Clin Microbiol Infect 2016;22(8):725-730. https://doi.org/10.1016/j.cmi.2016.06.006        [ Links ]

    3. Deiss RG, Bolaris M, Wang A, Filler SG. Cryptococcus gattii meningitis complicated by Listeria monocytogenes infection. Emerg Infect Dis 2016;22(9):1669-1671. https://doi.org/10.3201/eid2209. 160142        [ Links ]

    4. Almand EA, Moore MD, Jaykus LA. Virus-bacteria interactions: An emerging topic in human infection. Viruses 2017;9(3):1-10. https://doi.org/10.3390/v9030058        [ Links ]

    5. Hernandez-Milian A, Payeras-Cifre A. What is new in listeriosis? BioMed Res Int 2014;2014:1-7. https://doi.org/10.1155/2014/358051        [ Links ]

    6. Charlier C, Perrodeau É, Leclercq A, et al. Clinical features and prognostic factors of listeriosis: The MONALISA national prospective cohort study. Lancet Infect Dis 2017;17(5):510-519. https://doi.org/10.3410/f.727254731.793533940        [ Links ]

    7. Krawczyk-Balska A, Markiewicz Z. The intrinsic cephalosporin resistome of Listeria monocytogenes in the context of stress response, gene regulation, pathogenesis and therapeutics. J Appl Microbiol 2016;120(2):251-256. https://doi.org/10.1111/jam.12989        [ Links ]

    8. Mardis BA, Conley CS, Kyle JA. Listeriosis: An overview. US Pharm 2012;37(8):38-41.         [ Links ]

    9. Valckx WJARM, Lutgens SPM, Haerkens-Arends HE, Barneveld PC, Beutler JJ, Hoogeveen EK. Listeria endocarditis: A diagnostic challenge. J Investig Med 2017;5(2):1-3. https://doi.org/10.1177/2324709617698995        [ Links ]

    10. Rajalakshmi A, Gopalakrishnan R, Nambi PS, Rao PV, Ramasubramanian V Listeria in adults - truly rare or rarely diagnosed in India. J Assoc Phys India 2017;65:106-108.         [ Links ]

    11. Boyles TH, Bamford C, Bateman K, et al. Guidelines for the management of acute meningitis in children and adults in South Africa. S Afr J Epidemiol Infect 2013;28(1):5-15.         [ Links ]

    12. Goldberg E, Bishara J. Contemporary unconventional clinical use of co-trimoxazole. Clin Microbiol Infect 2012;18(1):8-17. https://doi.org/10.1111/j.1469-0691.2011.03613.x        [ Links ]

    13. Hof H, Nichterlein T, Kretschmar M. Management of listeriosis. Clin Microbiol Rev 1997;10(2):345-357.         [ Links ]

    14. Mitjá O, Pigrau C, Ruiz I, et al. Predictors of mortality and impact of aminoglycosides on outcome in listeriosis in a retrospective cohort study. J Antimicrob Chemother 2009;64(2):416-423. https://doi.org/10.1016/s0513-5117(10)79313-3        [ Links ]

    15. National Institute for Communicable Diseases, Division of the National Health Laboratory Service. Centre for Enteric Diseases. Listeriosis: Clinical recommendations for diagnosis and treatment, 2017. http://www.nicd.ac.za/wp-content/uploads/2017/12/Listeriosis_Clinical_Guidelines.pdf (accessed 4 December 2017).         [ Links ]

     

     

    Correspondence:
    C J Opperman
    stefanopperman1@gmail.com

    Accepted 18 December 2017