Linezolid and Clindamycin Improve the Outcome of Severe, Necrotizing

Le Infezioni in Medicina, n. 1, 42-44, 2011 Casi clinici Linezolid and clindamycin improve the outcome of Case reports severe, necrotizing pneumonia due to community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) L’associazione di linezolid e clindamicina migliora la prognosi delle gravi polmoniti necrotizzanti da Staphylococcus aureus meticillino-resistente di comunità (CA-MRSA)

Laura Soavi 1, Liana Signorini 2, Roberto Stellini 2, Annamaria Acquarolo 3, Bertilla Fiorese 2, Silvia Magri 2, Annalisa Pantosti 4, Fredy Suter 1, Giampiero Carosi 2 1U.S.C. Malattie Infettive, Ospedali Riuniti di Bergamo, Bergamo, Italy; 2Istituto di Malattie Infettive e Tropicali, Spedali Civili di Brescia, Brescia, Italy; 3Dipartimento di Anestesia e Rianimazione, Spedali Civili di Brescia, Brescia, Italy; 4Dipartimento di Malattie Infettive, Parassitarie ed Immuno-mediate, Istituto Superiore di Sanità, Rome, Italy

n INTRODUCTION tibiotics have different effects on the expression of staphylococcal toxins. Linezolid and clin - ethicillin-resistant Staphylococcus aureus damycin markedly suppress PVL production in (MRSA) is a major cause of nosocomial MRSA, whereas nafcillin and vancomycin stim - Minfection. The emergence of MRSA as a ulate continued PVL expression [5]. cause of life-threatening, invasive infections in the We here report a case of CA-MRSA necrotizing community in patients who never had healthcare pneumonia and septic shock, in which patient’s contacts is a recent, important public health prob - outcome was strongly influenced by the choice lem [1]. Such infections include, among others, of antibiotic therapy, providing clinical support septic shock and necrotizing pneumonia, which is to the findings of in vitro studies. rapidly progressive, haemorrhagic and often fatal (mortality rate: 60-75%) [2, 3]. The high virulence potential of CA-MRSA is as - n CASE REPORT sociated with the production of the Panton- Valentine leukocidin (PVL), a toxin that creates A previously healthy, caucasian, 49-year-old lytic pores in cells membranes of neutrophils woman became ill with fever and productive and induces release of neutrophil pro-inflam - cough on January 1 st , 2008. The next days her matory chemotactic factors which, in turn, symptoms worsened and, on January 6 th , she cause widespread tissue necrosis [4]. was taken to our Emergency Department (ED) A recent in vitro study evaluating the effect of in respiratory distress. On examination, she had vancomycin, nafcillin, clindamycin and linezol - a temperature of 38.5°C, an oxygen saturation of id on clinical isolates of Methicillin-susceptible 90% on room air, a blood pressure of 160/90 S. aureus (MSSA) and MRSA has shown that an - mmHg, a hearth rate of 86 beats per minute and

42 2011 tericin B-liposomal were replaced by van - comycin, rifampin and caspofungin. Four days thereafter, her lung oxygenation and haemody - namic parameters worsened, and chest X-ray re - vealed widespread bilateral alveolar infiltrates with multiple cavities in the upper right lobe. Doses of inotropes were increased and antibiot - ic therapy was changed: linezolid and clin - damycin replaced vancomycin and rifampin, caspofungin was continued. The patient’s con - dition progressively improved: she rapidly be - came afebrile, arterial blood gases, as well as leukocyte and platelet count, CRP and procalci - tonin, returned to normal values. On January 20 th , CVVH and mechanical ventilation were Figura 1 - CT scan of the thorax shows bilateral pul - discontinued and, after 5 more days, antibiotic monary infiltrates with one small cavitary lesion in therapy was stopped. the inferior, left lobe and enlargement of mediasti - nal lymph nodes. The patient was discharged on day 72: she is currently healthy with complete recovery of respiratory function. a respiratory rate of 35 breaths per minute. Ar - terial blood gases revealed a pH of 7.429, a PaO 2 of 57 mmHg and a PaCO 2 of 37 mmHg. Blood n DISCUSSION exams showed a creatinine of 1.4 mg/dl and a pro-inflammatory state (leukocyte count 13110 In the patient we described, the finding of lung cells/ µl, CRP 270 mg/l, procalcitonin 128.2 necrosis was consistent with the production of ng/ml). A CT scan revealed bilateral multiple PVL, later confirmed by PCR. We observed a alveolar infiltrates in all lung fields with a small clear relationship between different antibiotic cavitary lesion and enlargement of mediastinal regimens and clinical conditions of the patient, lymph nodes (Figure 1). She was started on in that ampicillin-sulbactam and vancomycin ampicillin-sulbactam and amphotericin B-lipo - were associated with worsening of respiratory somal. The patient worsened, failed to respond function and pulmonary infiltrates, whereas to oxygen supplementation and was admitted resolution of pneumonia was achieved only af - to the intensive care unit (ICU), where she was ter starting two toxin-suppressing agents, clin - intubated and put on mechanical ventilation. damycin and linezolid. Within hours, she became hypotensive, requir - The main reasons that explain why beta-lac - ing inotropic support, and developed pancy - tams and glycopeptides may fail in infections topenia (leukocyte count 3400 cells/ µl, platelet associated with toxin-producing organisms are count 95000/ µl) with multi-organ failure (MOF) that these cell-wall-active agents, in contrast to requiring continuous veno-venous hemofiltra - protein-synthesis inhibitors, do not suppress tion (CVVH). Because of septic shock, hydrocor - toxin production and that lysis of the bacteria tisone was added to the antimicrobial treatment. increases the release of intracellular toxins [5]. Bronchoscopy was performed, which showed These data suggest that, for treatment of MRSA abundant white secretions covering an edema - strains producing potent extracellular toxins, tous bronchial mucosa with focal necrosis and linezolid and clindamycin demonstrate a clear mild bleeding. On day 2, broncho-alveolar advantage over vancomycin. Linezolid, more - lavage (BAL) cultures were reported as growing over, has an excellent lung tissue penetration, S. aureus (>5 x 10 6 CFU/ml), later referred as which is approximately 6 times higher than that MRSA, and Aspergillus fumigatus . Antibiotic of vancomycin [6, 7]. therapy was immediately modified and linezol - Starting early appropriate antibiotic treatment id and levofloxacin were started, while continu - is considered essential to ensure a favourable ing liposomal amphotericin B. After 3 days of outcome, and highlights the importance of sus - therapy, while the clinical conditions of the pa - pecting CA-MRSA in previously healthy pa - tient seemed to improve, platelet count dropped tients presenting to ED with severe respiratory to 29000/ µl. Linezolid, levofloxacin and ampho - illness, especially when associated with pul -

43 2011 monary necrosis, septic shock, high fever, Key words: CA-MRSA, pneumonia, Panton-Va - haemoptysis and leucopoenia [8]. lentine leukocidin (PVL), linezolid, clindamy - Unlike the American counterpart, the latest Eu - cin ropean guidelines on CAP management do not take in consideration potential occurrence of Acknowledgements CA-MRSA [9, 10]. We believe that there is the The authors thank Dr. Alberto Matteelli for his crit - case to review them now. Surveillance of com - ical comments and his precious suggestions. munity acquired S. aureus and optimal treat - ment strategies are also required. Potential conflicts of interest: none declared.

SUMMARY

The last decade has been characterized by the septic shock caused by CA-MRSA, in which early emergence of CA-MRSA strains associated with recognition of the syndrome and appropriate treat - the production of Panton-Valentine leukocidin. ment with two toxin-suppressing antibiotics im - We report a case of necrotizing pneumonia and proved the patient’s outcome.

RIASSUNTO

Nell’ultimo decennio si è osservato un progressivo au - shock settico da CA-MRSA, in cui la diagnosi precoce e mento nell’incidenza di gravi infezioni causate da ceppi la terapia di associazione con antibiotici entrambi in di CA-MRSA associati alla produzione della leucocidi - grado di inibire la sintesi proteica (quindi anche la sin - na di Panton-Valentine. tesi della leucocidina) hanno determinato la pronta riso - Riportiamo un caso clinico di polmonite necrotizzante e luzione dell’infezione.

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