Cerebrospinal fluid shunt infections with anaerobic diphtheroids. (Propionibacterium species)

Transcription

1 Cerebrospinal fluid shunt infections with anaerobic diphtheroids (Propionibacterium species) E. DALE EVERETr, LT. COL., M.C., THEODORE C. EICKHOFF, M.D., AND RICHARD H. SIMON, M.D. Department of Medicine, Division of Infectious Disease and the Department of Neurosurgery, University of Colorado Medical Center, Denver, Colorado ~" The clinical and laboratory findings in six cases of anaerobic diphtheroid infection of cerebrospinal fluid shunts are described. These organisms have been infrequently reported as a cause of shunt infections but our data indicate that such infections may be more common than currently appreciated. Propionibacterium species are common contaminants of cerebrospinal fluid specimens, but when isolated from the spinal fluid of a patient with a shunt who has symptoms and signs compatible with infection, the organism should not be dismissed as a contaminant. Fever was a constant finding frequently accompanied by signs of central nervous system dysfunction. Spinal fluid pleocytosis was usually limited to 1 to 200 cells and protein and sugar values were variable. The organisms grow slowly, therefore spinal fluid cultures should be held for at least 14 days before they are reported as negative. KEY WORDS 9 shunt infections 9 anaerobic diphtheroids I NFECTIONS are a common and serious complication of cerebrospinal fluid shunts. A variety of species of micro-organisms have been responsible for these infections but by far, Staphylococcus epidermidis has predominated.2,5'11,1~ Anaerobic diphtheroids have been mentioned only briefly as a cause of shunt infection or colonization?,2,4,9 We report here the findings in six cases of anaerobic diphtheroid shunt infections that have been observed during the past 31/2 years. Materials and Methods We made a retrospective review of results from spinal fluid cultures performed during the past 31/2 years in microbiology labor- atories of Colorado General Hospital (CGH) and Denver Veterans Administration Hospital (DVAH). The presence or development of central nervous system (CNS) infection was determined by a review of the clinical records of patients from whom anaerobic diphtheroids were isolated from cerebrospinal fluid (CSF). A patient was accepted as a case of anaerobic diphtheroid shunt infection if there existed signs and symptoms of CNS infection, and CSF pleocytosis, with an anaerobic diphtheroid isolated as the only organism. Spinal fluid specimens were collected at the time of lumbar puncture, pneumoencephalography, ventriculography, and by aspiration from ventricular shunt mechanisms. The specimens were transported to the microbi- 580 J. Neurosurg. / Volume 44 / May, 1976

2 Anaerobic diphtheroid CSF shtmt infections TABLE 1 Clinical data in patients with anaerobic diphtheroid infection of CSF shunts Case Interval Between Reason for No. Surgery & Symptoms Shunt Type Shunt Presenting Signs & Symptoms 1 8 mos tumor ventriculoatrial 2 10 mos normopressure ventriculoperitoneal hydrocephalus 2 mos 3 18 days normopressure ventriculoatrial hydrocephalus 4 8 hrs tumor ventriculoatrial 5 3 mos tumor 9 mos 6 2 mos tumor ventriculoatrial ventriculoperitoneal temp 40 ~ C, seizure and stiff neck temp 38 ~ C, stiff neck temp 39 ~ c, shunt malfunction temp 39 ~ C, increasing disorientation, vomiting temp 38.6 ~ C, neck pain, intermittent confusion, abdominal pain temp 38.4 ~ C, headache, chills, stiff neck, and vomiting temp 38.7 ~ C, vomiting, headache decrease in recent memory temp 37.8 ~ C, stiff neck, somnolent, decreasing memory ology laboratories in a routine manner and cultured aerobically and into thioglycollate broth. In addition, at one hospital (DVAH), spinal fluid was also inoculated to prereduced media in an anaerobic chamber. Spinal fluid cultures were observed for 7 days at CGH and for 30 days at DVAH laboratories, Gram-stained, and if no organisms were noted, discarded. Anaerobic diphtheroid isolates were identified by their Gram-staining characteristics, inability to grow aerobically, biochemical testing, and gas-liquid chromatography. Results At one of the hospitals (DVAH), a total of 1616 spinal fluid specimens was cultured over the past 31/2 years. Of these, 30 (1.9%) were positive for anaerobic diphtheroids. Only three (0.19%) of these specimens (two from the same patient) were considered significant. From the CGH laboratory, 311 spinal fluid cultures were positive for some species of micro-organism, and 109 (35%) of these were anaerobic diphtheroids. The time for these contaminating organisms to result in positive cultures varied from 1 to 13 days (mean 6.4 days). During the period of time encompassed by this review, approximately 350 shunts were inserted or revised, and there were six confirmed and three probable cases of Propionibacterium shunt infections. The latter cases are not included because of inadequate data. All six patients with confirmed infections were adults ranging in age from 21 to 68 years; the sex distribution was equal. All of these patients had had insertion of Denver shunts with Rickham reservoirs.* As a routine preparation prior to placement of a shunt, the entire scalp was shaved, followed by an 8-minute scrub with povidoneiodine soap. The skin was painted twice with acetone and then germasan iodine was applied twice. Four had ventriculoatrial and two ventriculoperitoneal shunts. All of the patients had received prophylactic antibiotics after placement of the shunt, usually consisting of methicillin (1 gm every 6 hours intravenously for 24 to 48 hours) followed by dicloxicillin (500 mg orally) to complete a 7- day course. No cases of primary Propionibacterium meningitis were discovered in this review. The clinical data are summarized in Table 1. The interval between time of insertion of the shunt and the onset of signs and symptoms of infection varied from hours to months with the latter predominating. Fever was a constant finding and signs of CNS dysfunction were almost always present. The *The Denver shunt is manufactured by Denver Biomaterial, Incorporated, Englewood, California J. Neurosurg. / Volume 44 / May, ]

3 E. D. Everett, T. C. Eickhoff and R. H. Simon TABLE 2 Laboratory data from patients with anaerobic diphtheroid infection* Case No. Peripheral CSF CSF Gram Time for Culture & Dates WBC Count Findings Stain to Become Positive cells--200 NR 9 days 8/11/71 82 segs 3 bands 66~o segs sugar--42/ lymphs protein--qns 2 12,700 cells--24 NR 9 days 6/27/74 88 segs 50Z segs 2 bands sugar--83/nr 10 lymphs protein--54 mgto 9/13/74 12,800 ceus--nr NR 5 days 79 segs sugar--75/nr 21 lymphs protein--8 mg~o 9/18/74 cells--124 NR negative 787o--polys sugar--nr protein ,400 cells--16,300 pleomorphic 3 days 9/20/71 85 segs 927o--polys Gram-positive 15 lymphs sugar--59/195 rods protein ,000 cells--nr NR 7 days 8/13/74 75 segs sugar--80/nr 5 bands protein lymphs 8/20/74 cells--218 negative 3 days sugar + protein--nr 5 10,100 cells--147 NR 4 days 1/6/74 87 segs 55 7o segs 3 bands sugar---qns 10 lymphs protein--109 mg 4/8/74 13,500 cells--222 Gram-positive 7 days 91 segs 43 7o segs rods 9 lymphs sugar--59/107 protein--28 mg~o 4/26/74 cells--96 Gram-positive 5 days 6 ~ segs rods 6 6,100 cells--315 negative negative 1/10/75 66 segs 5 bands 887o segs sugar---42/70 29 lymphs protein--51 mgto 1/17/75 cells--178 Gram-negative 5 days segs rods sugar--31 / 128 protein /29/75 NR NR 5 days * CSF sugar/blood sugar. NR=not recorded. QNS = quantity not sufficient. onset of symptoms varied from insidious to abrupt. A summary of the laboratory findings is presented in Table 2. These data indicate that there is usually a mild peripheral leukocytosis, with a shift toward neutrophilia, pleocytosis ranging from a few to thousands of cells with polymorphonuclear cells pre- 582 J. Neurosurg. / Volume 44 / May, 1976

4 Anaerobic diphtheroid CSF shunt infections dominating, and sugar and protein content variable. Profound hypoglycorrhachia did not occur. Results of Gram stain were recorded only six times and in four instances were positive for organisms. In one case, the Gram stain was read as Gram-negative rods but was subsequently found to be Propionibacterium acnes. The time for cultures to become positive varied from 3 to 9 days (mean 5.6 days). One of five patients from whom blood cultures were obtained had positive cultures which did not grow out until the tenth day of incubation. Treatment of our cases was highly varied, but consisted of multiple courses of systemic antibiotics, removal of shunts, and repeated revisions or replacement of shunts under antibiotic coverage. Three of the cases were not recognized by the primary physician as anaerobic diphtheroid infections. Two of these patients survived after multiple antibiotic regimens and surgical procedures. One died (Case 1) as a result of complications of his infection while being treated with penicillin. Another (Case 3) died of unrelated causes 7 months after successful treatment of her infection by shunt removal and penicillin. The remainder are doing well at the time of this report with follow-up ranging from 1 to 12 months. Discussion The overall incidence of CSF shunt infections in one large series of approximately 500 patients with shunts has been estimated to be 7% during the first year after placement and an additional 5% over the ensuing 5 years. A large number of papers have been written concerning shunt infections but have dealt almost exclusively with staphylococcal infections, primarily Staphylococcus epidermidis.2.sm,ls Anaerobic diphtheroids, currently classified as Propionibacterium species, like Staphylococcus epidermidis, are of low virulence and ubiquitous on the skin; in fact the former outnumber the latter by 10- to 100-fold? The organisms are most numerous in areas of the skin containing pilosebaceous glands, with the scalp being the most heavily colonized. 7 Shunt infection with Propionibacterium species has been uncommonly reported with only a few cases, varying from asymptomatic colonization found at the time of elective removal of shunts and mixed in- fection with Staphylococcus epidermidis to symptomatic disease. 1,2,4,9 The exact pathogenesis of CSF shunt infection has not been elucidated but many are thought to originate from colonization at time of surgery? ~ If this is true, one wonders why anaerobic diphtheroids have not been more commonly encountered as a cause of shunt infections. There may be several possible explanations for this: 1) spinal fluids may not be routinely cultured in thioglycollate broth or anaerobically, 2) cultures may not be held a sufficient length of time for growth, 3) the isolation of the organism may be ignored as a contaminant by the clinician, 4) the physician may not recognize the organism as being a cause of CNS infection, and 5) perhaps Propionibacterium species are unusual causes of shunt infections. Since 1.4% of all shunts placed or revised at our hospitals became infected with anaerobic diphtheroids, the latter explanation seems unlikely. In our cases, the clinical onset was either abrupt or insidious, however, the course was indolent when viewed in relation to the classical causes of bacterial meningitis. The typical patient had had a shunt inserted 2 or more months prior to the onset of symptoms, invariably had fever, and almost always signs of CNS dysfunction particularly in mentation. In Case 5, the patient developed a shunt infection 3 months after surgery that spontaneously resolved over 3 days then relapsed 6 months later. Laboratory data disclosed a mild peripheral leukocytosis, usually moderate pleocytosis with a predominance of neutrophils and absence of profound hypoglycorrhachia. Gram stains when performed were frequently positive. The major clinical clue to the possibility of Propionibacterium infection was the presence of a shunt. Based on our data, the following recommendations can be made concerning diagnosis of anaerobic diphtheroid infections. Spinal fluid specimens should always have complete routine examination to include a Gram stain and be cultured aerobically and at least in thioglycollate broth. Cultures should be held for a minimum of 14 days since at least two of our cases did not have positive cultures until after 9 days of incubation. Anaerobic diphtheroids are common contaminants but in a patient with a ventricular J. Neurosurg. / Volume 44 / May,

5 E. D. Everett, T. C. Eiekhoff and R. H. Simon shunt who has signs of infection and CSF pleocytosis, the isolation of these organisms should not be ignored. Although not supported by our data, it would seem prudent, in cases where clinical and laboratory findings of shunt infection are present but cultures are negative, to undertake special anaerobic culture methods. This would include collection of spinal fluid in an anaerobic tube for transport to the laboratory and inoculation to prereduced media as well as thioglycollate broth. Blood cultures should of course be performed, but these were positive in only 20% of our cases. If it becomes necessary to remove the shunt apparatus, all components should be cultured anaerobically as well as aerobically. Complications other than difficulty in eradicating the infection were few in our cases providing the case was recognized as an anaerobic diphtheroid infection. One patient died as a result of his infection. Another patient developed a Staphylococcus epidermidis infection following her initial diphtheroid infection. Glomerulonephritis, a wellrecognized complication of staphylococcal shunt infections, TM was not seen in our cases but has been reported by others? Because this is a retrospective study and treatment was varied, we cannot make definitive statements pertaining to the best method of treatment. Propionibacterium species (the most studied being Propionibacterium acnes) are universally sensitive in vitro to penicillin, chloramphenicol, clindamycin, and rifampin. Almost all are sensitive to cephalothin, erythromycin, and tetracyclines) 's It would seem reasonable to approach treatment of Propionibacterium shunt infections in the same manner as outlined by Shurtleff, et al.? s for Staphylococcus epidermidis infections. References 1. Beeler BA, Crowder JG, Smith JW, et al: CNS shunt infections with Propionibacterium. Presented at the 14th International Conference on Antimicrobial Agents and Chemotherapy, San Francisco, California, September Bruce AM, Lorber J, Shedden WIH, et al: Persistent bacteremia following ventriculocaval shunt operations for hydrocephalus in infants. Dev Med Child Neuroi 5: , Chow AW, Patten V, Guze LB: Comparative susceptibility of anaerobic bacteria to minocycline, doxycycline and tetracycline. Antimicrob Agents Chemother 7:46-49, Fokes EC Jr: Occult infections of ventriculoatrial shunts. J Neurosurg 33: , Holt R: The classification of staphylococci from colonized ventriculo-atrial shunts. J Clin Pathol 22: , Marples M J: The Ecology of the Human Skin. Springfield, I11: Charles C Thomas, 1965, chap Marples RR, McGinley K J: Corynebacterium acnes and other anaerobic diphtheroids from human skin. J Med Microbiol 7: , Martin W J, Gardner M, Washington JA 2nd: In vitro antimicrobial susceptibility of anaerobic bacteria isolated from clinical specimens. Antimicrob Agents Chemother 1: , Nastasi G, Filizzolo F, Bavastrelli L, et al: Colonization of Spitz-Holter valves by rare bacterial flora. Aeta Neurochir 26: , Nicholas JL, Kamal IM, Eckstein HB: Immediate shunt replacement in the treatment of bacterial colonisation of Holter valves. Dev Med Child Neurol [Suppl] 22: , Nulsen FE, Becker DP: Control of hydrocephalus by valve-regulated shunt: infections and their prevention. Clin Neurosurg 14: , Schimke RT, Black PH, Mark VH, et al: Indolent Staphylococcus albus or aureus bacteremia after ventriculoatriostomy. N Engi J Med 264: , Shurtleff DB, Foltz EL, Weeks RD, et al: Therapy of Staphylococcus epidermidis: infections associated with cerebrospinal fluid shunts. Pediatrics 53:55-68, Stauffer UG: "Shunt nephritis:" diffuse glomerulonephritis complicating ventriculoatrial shunts. Dev Med Child Neurol [Suppi] 22: , 1970 Address reprint requests to: E. Dale Everett, M.D., Division of Infectious Disease, Box B168, University of Colorado Medical Center, 4200 East 9th Avenue, Denver, Colorado J. Neurosurg. / Volume 44 / May, 1976