Journal of Infection and Public Health (2016) 9, 192—197

CASE REPORT

Nocardia asteroides peritonealdialysis-related peritonitis: First case inpediatrics, treated with protractedlinezolid

Mohamed El-Naggari a,∗, Ibtisam El Noura,Dana Al-Nabhania, Zakaria Al Muharrmib, Heba Gaafarc,Anas A.W. Abdelmoghetha

a Sultan Qaboos University Hospital, Child Health Department, Omanb Sultan Qaboos University Hospital, Microbiology Department, Omanc Sultan Qaboos University Hospital, Pharmacy Department, Oman

Received 3 May 2015; received in revised form 6 August 2015; accepted 1 November 2015

KEYWORDSContinuous ambulatoryperitoneal dialysis;Peritoneal dialysis;Intra-abdominalabscess;Nocardia asteroides;Peritonitis;

Summary Nocardia asteroides is a rare pathogen in peritoneal dialysis-relatedperitonitis. We report on a 13-year-old female with Nocardia asteroides peri-tonitis complicated by an intra-abdominal abscess. Linezolid was administeredintravenously for 3 months and followed by oral therapy for an additional 5 monthswith close monitoring for adverse effects. The patient was discharged after 3 monthsof hospitalization on hemodialysis. The diagnosis and management of such cases canbe problematic due to the slow growth and difficulty of identifying Nocardia species.The optimal duration of treatment for Nocardia peritonitis is not known. Linezolid

Omancan be used for prolonged periods in cases of trimethoprim/sulfamethoxazole-resistant cases with close monitoring for adverse effects.© 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by ElsevierLimited. All rights reserved.

∗ Corresponding author at: Sultan Qaboos University, ChildHealth Department, PO Box 35, Al-Khod 123, Oman.Tel.: +968 98178236; fax: +968 24144103.

E-mail address: mnaggari@yahoo.com (M. El-Naggari).

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http://dx.doi.org/10.1016/j.jiph.2015.11.0031876-0341/© 2015 King Saud Bin Abdulaziz University for Health Scie

ntroduction

eritoneal dialysis (PD) is a widely used modal-

ty for renal replacement therapy. Peritonitis is aommon problem in patients undergoing continuousmbulatory peritoneal dialysis (CAPD) and repre-ents the most frequent cause of hospitalization

nces. Published by Elsevier Limited. All rights reserved.

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ocardia asteroides peritoneal dialysis-related peri

eritoneal catheter loss, technique failure, dis-ontinuation of CAPD, and mortality are exhibitedy these patients. Staphylococcus species are usu-lly implicated in infectious cases of peritonitis inatients undergoing CAPD. Fungi and higher bacte-ia such as Nocardia asteroides are less frequentausative agents [1].

Nocardiosis was named after the French veteri-arian Edmond Nocard in the late 1800s and is annfection caused by gram-positive aerobic bacteriaf the genus Nocardia [2]. Despite its universal pres-nce in soil, organic matter and water, Nocardia is aare pathogen of PD-related peritonitis [2]. Humannfections are primarily observed in immunocom-romised hosts and typically originate in the lungsnd then spread to other organ systems, includinghe brain, skin and kidney [4].

Linezolid is a synthetic oxazolidinone, which is novel class of antibiotics with clinical utility inhe treatment of infections caused by gram-positiveerobic bacteria. Linezolid binds to a site on theacterial 23S ribosomal RNA of the 50S subunit torevent the formation of a functional 70S initia-ion complex, which is an essential component ofhe bacterial translation process. Linezolid is pri-arily indicated for the treatment of infections

aused by resistant gram-positive organisms partic-larly methicillin-resistant Staphylococcus aureusnd vancomycin-resistant Enterococcus species.inezolid also exhibits in vitro activities againstome gram-negative anaerobes and mycobacterialpecies, including Mycobacterium tuberculosis andocardia spp. [5—7]. Here, we report the first casef Nocardia asteroides peritonitis in a pediatricatient who was treated with a protracted coursef linezolid.

ase report

13-year-old female had been receiving CAPDor 3 years due to diffuse global sclerosis com-licated by end-stage renal failure. She also hadamilial leukodystrophy with cerebellar ataxia andyramidal features. She presented with high-gradeever, leakage from the exit site of the perit-neal catheter, and diffuse abdominal pain for 7ays. She was admitted with a suspected catheterxit-site or tunnel infection complicated byeritonitis.

On presentation, she was lethargic, tachypneic40—45 breaths/min) with no respiratory distress,

achycardic (heart rate 125—135 beats/min), with

temperature of 40.2 ◦C. Her weight was 18 kgbelow the 3rd percentile for age and sex). Physicalxaminations were all within normal limits except

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or generalized, mild abdominal tenderness andeurological findings consistent with the primaryisease. The exit site exhibited no inflammation,ut there was marked dialysate leakage. The lab-ratory data revealed the following: white cellount 10,300/mm3, hemoglobin 5.9 g/dL, platelets05,000/mm3, C-reactive protein 146 mg/L, albu-in 24 g/L, ALT 15 U/L, AST 24 U/L, Na 125 mmol/L,

3.6 mmol/L, bicarbonate 17 mmol/L, creatinine47 �mol/L, and urea 20.9 mmol/L. The dialysateas turbid with white sediment, and the leukocyteount 300/mm3 (neutrophils 90% and lymphocytes0%). Gram-stain of the dialysate revealed gram-ositive bacilli, and a modified Kinyoun stainevealed partially acid-fast branching bacilli. Inlood agar, the colonies exhibited a chalky white,otton candy appearance with reductus on the sur-ace, which denoted Nocardia species. The isolateas ultimately identified as Nocardia species after

weeks of incubation.The running peritoneal dialysis prescription was

or Bicavera peritoneal fluid at a 1000-ml volume,0-min input, indwelling time of 4 hr and an outputf 20 min. We used an alternating cycle of 1.5% and.3% for a total of 5 cycles. We used rapid cyclesn and out with no rest indwelling time until theuid was clear because the fluid was still turbid andull of sediment. Next, we initiated a 1.5-h cycle10 min input with an indwelling time 1 hr and out at0 min) with a small volume of 600 ml 1.5% glucose.

short-cycle regimen and small fill volume weresed for more efficient dialysis and to decreasehe dialysate leakage. The patient was initiatedn intraperitoneal vancomycin, ciprofloxacin andntravenous (IV) cloxacillin. Amphotericin-B wasdded after 4 days due to suspected fungal peritoni-is. Because no clinical improvement was observed,iprofloxacin was replaced with intraperitoneal cef-azidime, the IV cloxacillin was stopped, and IVeropenem and amikacin were added. The childent into cardiac arrest and septic shock after0 days of conservative management with the dif-erent antibiotic regimens. A peritoneal culturerew Nocardia asteroides after 2 weeks that exhib-ted sensitivity to linezolid, imipenem and amikacinnd resistance to trimethoprim-sulfamethoxazole.epeated blood culture revealed no growth witho isolation of organisms even after a prolongedncubation period.

The catheter was removed, and the child wasanaged in the pediatric intensive care unitith continuous venovenous hemofiltration (CVVH),

echanical ventilation and inotropic support. CVVHas performed because the child was very sick, andonventional pediatric hemodialysis is not avail-ble in our institute. The case was complicated

194 M. El-Naggari et al.

Figure 1 Abdominal U/S revealing an abscess in lowerabdomen in the left iliac fossa.

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Figure 2 CT-ABD: sagittal section revealing lower leftiliac abscess.

by a peritoneal abscess following the removalof the catheter. Abdominal ultrasound revealedan intraabdominally localized collection that wasevacuated by ultrasound-guided aspiration (Fig. 1).Jejunal adhesions with some feeding intolerance

were treated conservatively (Figs. 2 and 3).

Linezolid was commenced based on drug sensi-tivity findings and the critical clinical situation ofthe child despite the cost, the paucity of literature

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igure 3 CT-ABD: cross-section revealing a lower leftliac abscess with free intra-abdominal collection.

n linezolid in other Nocardia infections, and theact that it had never been used for Nocardia peri-onitis. The guardian consented to the use linezolidfter counseling regarding these issues. Linezolidas intravenously administered (10 mg/kg BID) for 3onths in the hospital. Good clinical improvementas observed, and weaning and extubation were

uccessfully performed. The patient was closelyonitored for treatment-related adverse effects,

ncluding myelosuppression. Hematological abnor-alities in the forms of anemia, thrombocytopenia

nd leucopenia are early side effects that haveeen reported with linezolid therapy. Serial fulllood counts were performed and found to beormal. The patient was discharged home after

months of hospitalization and rehabilitation onemodialysis and tolerated oral and small boweleeding. Linezolid oral therapy (10 mg/kg BID) wasontinued for 5 months, and no side effects wereeported. A prolonged duration of treatment withinezolid was anticipated given that Nocardia infec-ion has a high incidence of recurrence.

iscussion

ocardia is an uncommon cause of PD-related peri-onitis. The species of the genus Nocardia areram-positive branching bacteria that belong to therder Actinomycetales. These bacteria are ubiqui-

ous in the environment and are found in the soil,n fresh and salt water, and in decaying vegeta-ion. Most Nocardia infections in humans are caused

Nocardia

asteroides peritoneal

dialysis-related peritonitis

195

Table 1 Summary of previous reports of Nocardia CAPD peritonitis.

Author (year)(Ref.)

Age Sex Cause ofESRD

Organism Incubationperiod

CAPDduration(years)

Previousperitonitisevent(s)

Medical treatment Catheterremoval

Arfania et al. [3] 70 M CIN N.asteroides

— 1 1 IP sulfisoxazole 6 weeks No

Chan et al. [10] 60 M PCKD Nocardiaspp.

5 Weeks 5 2 IP TMP-SMX 3 weeks No

Kaczmarski et al.[11]

58 F NA N.asteroides 6 days 2 10 IP/IV ceftazidime + netilmicin2 weeks

Yes

Lopes et al. [12] 38 M SLE N.asteroides

7 days 6 2 IP TMP-SMX 4 weeks No

Recule et al. [13] 80 M NA Nocardianova

4 days 1.5 3 After removal ofcatheter,oral TMP-SMX 3weeks

Yes

Dwyer et al. [14] 32 M Type 1 DM Nocardianova

1 week 6 6 1 week antibiotic Yesa

Chu et al. [15] 68 F NA Nocardiaspp.

4 days 4 0 IP TMP-SMX + IV ceftriaxone 2weeks

Nob

Ortiz et al.* [16] 35 M CBUS N.asteroides

— 2.5 0 IV TMP-SMX + IP Amikacin 5weeks, Oral Cefruxime + IPAmikacin 12 weeks.

No

Li et al. [17] 75 M Type 2 DM Nocardiaspp.

2 weeks 1 0 Oral TMP-SMX 4 weeks, IPTMP-SMX 3 weeks

Yes

Jones et al. [18] 66 M Type 2 DM N.asteroides

3 weeks 3 1 IP cephazolin andgentamicin, Oral TMP-SMX

Yes

Prasad et al. [19] 52 M Type 2 DM N.asteroides

— 1.5 2 IP TMP-SMX 4 Days, IVCeftriaxone + Ciprofloxacin 2weeks

Yesc

Current case 12 F DGS N.asteroides

2 weeks 3 1 IP van-comycin + cipro/ceftazidime2 wk, IV linezolid 3 M, oral 5 M

Yesd

CAPD = continuous ambulatory peritoneal dialysis; ESRD = end-stage renal disease; CIN = chronic interstitial nephropathy; PCKD = polycystic kidney disease; NA = not available;SLE = systemic lupus erythematous; DM = diabetes mellitus; Rx = prescription; IP = intraperitoneal; TMP-SMX = trimethoprim-sulphamethoxazole; IV = intravenous; CBUS = congenital bilat-eral ureteral stenosis; DGS= diffuse global sclerosis.

a Intra-abdominal abscess occurred 10 days after catheter removal, requiring surgical drainage and 4 months of IV imipenem treatment.b Died of myocardial infarction before IP antibiotic treatment was complete.c Died of relapsing peritonitis after 2 weeks of admission, associated with Nocardia pneumonia.d Complicated with intra-abdominal abscess that need drainage.* APD = Automated Peritoneal Dialysis.

Rubin et al. [20] reported one case of Nocardia peritonitis in CAPD patient.

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by N. asteroides, N. nova, N. farcinica, and N.brasiliensis. The majority of patients with clinicallyrecognized disease have underlying predisposingfactors [4]. Our patient had potential environmen-tal exposure through her rural lifestyle, and wespeculate that contaminated soil or water contain-ing Nocardia was introduced into the peritoneumvia her PD catheter or she had a tunnel infection dueto touch contamination. Unusual organisms must beconsidered when PD peritonitis is culture-negativeor refractory to standard antibiotic treatment.

To the best of our knowledge, there are 10 casereports of Nocardia CAPD peritonitis and only onecase report of a patient on automated PD in theliterature (Table 1). Decisions regarding catheterremoval appear to be crucial in the managementof peritonitis. Successful treatment of Nocardiaperitonitis has been reported with and withoutPD catheter removal. The catheters have beenremoved in five of the 11 patient cases reportedthus far.

Moylett et al. [5] reported six cases of Nocardiatreated with linezolid, and all of these cases werecured. Linezolid was used as monotherapy in fourof these cases. Two pediatric cases at ages of 6 and9 years were diagnosed as chronic granulomatousdisease with pneumonia and disseminated Nocar-dia, respectively. Linezolid was used for 24 monthsin the first and 12 months in the second case withcomplete cure and no reported adverse effects.Therefore, linezolid therefore appears to be aneffective alternative for the treatment of nocar-diosis. Shen et al. [7] reported 14 cases of Nocardiathat were treated with linezolid, and 13 cases wereconfirmed to have achieved clinical cure.

In an evaluation of linezolid treatment in 447children, Chiappini et al. [8] reported variable clin-ical cure rates ranging from 77.5% to 90.0% inchildren with bacteremia or pneumonia. The mostfrequently reported adverse events were diarrhea(incidence 3.1—16.8%), nausea and/or vomiting(2.9—11.9%), and thrombocytopenia (1.9—4.7%).To date, three cases of neuropathy have beendescribed in children.

Garazzino et al. [9] studied the clinical experi-ence of linezolid use in infants and children (611children in four clinical trials and 206 children incase reports and case series aged up to 17 years).Thrombocytopenia occurred in 1.9% of the patients,anemia in 1.4% of the patients, and neutropenia innone of the patients. Four cases of peripheral andoptic neuropathy in children have been reported

thus far. Nocardia infection generally presents asan infection that is unresponsive to empirical treat-ment and initially appears as ‘culture-negative’peritonitis. The diagnosis and management of

M. El-Naggari et al.

ocardia infection can be problematic due to thelow growth and difficult identification of Nocardiapecies. The choice of therapy should be deter-ined based on local sensitivity patterns. Linezolidas used in this study because there was no alter-ative agent; linezolid can be used in the pediatricge group over the long-term without side effectsf monitoring is performed. Additionally, long-termreatment with linezolid requires at least one yearf no complications are observed.

onclusion

e report the first case of Nocardia asteroideseritonitis in a pediatric subject who was success-ully treated with the administration of linezolidor eight months under monitoring without any sideffects. Catheter removal and shifting to hemodial-sis should be considered for patients who do notespond to intraperitoneal antibiotics.

The optimal duration of treatment for Nocar-ia peritonitis is not known; however, a prolongedreatment course is necessary due to the occur-ence of a considerable number of relapsesollowing shorter courses of therapy. Linezolid cane used in pediatric patients for prolonged periodsn trimethoprim/sulfamethoxazole-resistant casesith close monitoring for adverse effects.

unding

o funding sources.

ompeting interests

one declared.

thical approval

ot required.

eferences

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ocardia asteroides peritoneal dialysis-related peri

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