Quarterly Journal of Medicine, New Series 78, No. 287, pp.

235-250, March 1991

Non-typhoid Salmonella in Renal Transplant

Recipients: a Report of Twenty Cases and
Review of the Literature
JM DHAR, AA AL-KHADER, M AL-SULAIMAN, AND MK AL-HASANI
From the Department of Nephrology, Riyadh Armed Forces Hospital,
P.O. Box 7897, Riyadh 11159, Kingdom of Saudi Arabia

Accepted 1 October 1990

SUMMARY
We report 20 cases of non-typhoid Salmonella infection that occurred over a period of 10 years
in 592 renal transplant recipients followed by our unit, and present a review of 58 previously
reported cases. Analysis of these data suggests that infection occurs when immunosuppression is
high (early in the post-transplant period, or after anti-rejection therapy). A significant number
of patients have bacteraemia and widespread focal manifestations are common. Despite
prolonged antibiotic therapy, relapses occur commonly causing significant morbidity, occasio-
nal graft loss and even death.

INTRODUCTION
Non-typhoid Salmonella produces a benign self-limiting infection in healthy adults [1-5];
however, such infection has an atypical presentation and causes significant morbidity and
even mortality in patients with defective cell-mediated immunity, such as those with
malignancies [6-10] or acquired immune deficiency syndrome [11-17] and renal transplant
recipients [18-32]. Despite this, there are only a few small reported series and single case
reports of non-typhoid Salmonella infection in renal transplant recipients. This paper
describes our experience with these organisms in our renal transplant population and
reviews the literature.

MATERIALS AND METHODS

Between the inception of the Riyadh Armed Forces Hospital renal transplant programme in
1979, and October 1989, 336 transplants were performed. An additional 256 patients
transplanted in India, UK, USA and elsewhere, have been studied, making a total of 592
patients seen in our renal transplant clinic. Patients transplanted abroad were seen by us
after a period of two weeks to one year (mean 3 months) post-transplant. Immunosuppres-
sive therapy consisted of a standard combination of azathioprine and prednisolone, until
1985, when a combination of cyclosporin A and low-dose prednisolone was introduced.
Some of the patients transplanted abroad receive a combination of prednisolone,

© Oxford University Press 1991

236 JM Dhar and others
azathioprine and cyclosporin A (triple therapy). The actuarial patient and graft survival of
our transplant population at one year are 93.7 per cent and 86.5 per cent, respectively and at
five years, 90.7 per cent and 80.9 per cent respectively.
A retrospective study was set up to determine the incidence, clinical presentation,
treatment and sequelae of infection by non-typhoid Salmonella in these patients. Twenty
patients were identified and the following data were extracted from the medical records: age,
sex, aetiology of renal failure, evidence of bilharziasis, gastric surgery, liver disease, antibody
to human immunodeficiency virus (HIV), hepatitis B status, treatment with H2-receptor
blockers, sickle status, place and type of transplantation, donor status, immuno-suppressive
regimen, length of time between transplantation and infection, clinical features, complica-
tions, recurrences, prior anti-rejection therapy, and transplant function before, during and
after treatment of infection. Cultures were obtained from blood, urine, stool and other
sources as indicated. Standard microbiological procedures were used to isolate and identify
the non-typhoid salmonellae. A source of persistent infection was sought in patients with
recurrent infection. It was not possible to identify the primary source of infection. Use of
standard isolation techniques ensured that there was no patient to patient spread.

PATIENT DETAILS (Table 1)

Twenty patients were infected with non-typhoid Salmonella, an incidence of 3.4 per cent in
our transplant population of 592. During the study period, the annual incidence and severity
of infection declined. There were 13 males and seven females aged from 4 to 63 years (mean
28.4 years) at the time of transplantation; all cases except one {Patient 2) occurred in
recipients of first transplants. Eleven patients were transplanted in our hospital (four living
related, seven cadaveric kidneys, including an explanted kidney: Patient 8 [33]) and nine
patients were transplanted abroad (five cadaveric transplants from the USA and four living
non-related transplanted in India). The cause of renal failure was unknown in eight patients
who had bilateral non-obstructed smooth shrunken kidneys. Eight patients had chronic
glomerulonephritis and there was one patient each with interstitial nephritis, cystic renal
disease, congenital hypoplastic kidneys and primary oxalosis. No patient had bilharziasis or
stone disease. Four patients were HIV-positive andfivehad evidence of liver disease, four of
whom were carriers of HBsAg (including one who was HBeAg positive). There was one
patient each with sickle trait and previous gastric surgery. Nine patients were taking H2-
receptor blocking agents and/or antacids at the time of presentation, and one patient had
steroid-induced diabetes mellitus requiring insulin treatment. Two patients had a bilateral
nephrectomy before transplantation and one patient had a left nephrectomy, a splenectomy
and a cholecystectomy. There was no evidence of infection by non-typhoid Salmonella in
donors of four living related transplants carried out.

CLINICAL FEATURES
Patients presented one week to 37 months post-transplant (mean ten months); fourteen
patients (70 per cent) presented within six months. The early presenters included seven
patients who presented within six weeks, two of which presented within two weeks of
cadaveric transplantation. Each of these had primary graft non-function, one due to acute
tubular necrosis and the other due to a combination of acute cellular and humoral rejection.
The later presenters included one patient each with deteriorating transplant function and
liver disease {Patient /), multiple courses of pulse methylprednisolone {Patient 2), hepatitis
B-induced chronic liver disease {Patient 9) and chronic rejection with serum creatinine of 400
TABLE 1. Non-typhoid Salmonella infection in renal transplant recipients at Riyadh Military Hospital, Kingdom of Saudi Arabia
Patient. N o Immunosupprcssion HIV Time Clinical feature Source o f culture Crealininc Treatment Outcome
( A g e Sex) antibody post-transplant Ornol/1)
Diagnosis Fever Diarrhea Othcn Blood Stool Unne Pin
Pre During Peat

1 (13. M) Bil. Ncphrcctomy. Aza + P 37 months Yes Yes Multiple + + - + 480 560 - Cefotaxime + Died
Primary 8/82 Cadaver j r a f l abscesses Nelilmicin + (septicaemia,
Oialosui (US). Amoxyallin DIQ
2(47. F) Cholecystcctomy, 12 months Yes No No 265 290 270 Amoxyallin Died 23 Months
GN 1/84 cadaver grafl + CsA + P 14 months Yes Yes No - 340 400 350 Amoxyallin post-transplant
iplenectomy. (US) 18 months Yes Yes No
I I - 300 300 310 Amoxyallin + (hepatic failure)
Chrome rejection, + Aza Ccfotnxime
hepatic dysfunction Aia>Cycto

3(3I.M) 10/84 Living non- C«A + P 6 months No Yes No — — 90 98 92 Amoxyallin No further

UA Related graft ( 1 N D ) 20 months No Yes No 110 120 100 Amcuyallin recurrence,
42 months Yo Yes Severe = x 190 470 200 Amoxydllin SCr 180/imol/l
Dehydration Cefolajiime +

4 (20. M) 11/84 Cadaver graft ClA + P 2 weeks Yes No Dysuna A - — + - Primary non- Amoxyallin Graft lost
UA ( R A F H ) Acute cellular pain over function
& humoral rejection. + Aza transplant

5(38. M) 11/84 Cadaver g r i ft C«A + P 6 months Yes No Dysuria & 360 378 350 AmoxyalUn Intermit ten ily
GN (RAFH) Pain over positive urine A
Transplant stool cultures
11 months Yes Yes No 280 288 295 Amoxyallin until 1/83
22 months Yes Ye» No I X - 260 290 260 Amoxydllin + SCr 250 pmol/1
Netilmicin
6(4. F) 12/84 Cadaver graft
Hypo- (US) CsA + P + Aza 37 months Yes No Pulmonary
+ - - 75 96 71 Amoxydllin + No recurrence
plastic Infection
- Nctilmicin SCr 70 /.mol/1
Kidneys
7(13. F) 7/85 Cadaver graft CsA + P 4 months Yes No Lympb-
+ 210 230 Amoxyalbn Immunosupprcssion
— - —
Cystic (RAFH) adenopathy discontinued
Renal (extensive Kaposi
Disease sarcoma) graft lost.

8 (63. M ) Left nephrectomy; CxA + P 1 week Yet No Sepuc arthritis + 900 230 165 Amoxya!lin + D k d 9 months
IN 12/85 cadaver graft Netilmidn poft-iranspUnt
TB (RAFH) 8 weeks Yes Yes Septic a n h n t i j + + - - + 165 240 150 Amoxydllin + (myocardial
pulmonary Cefolaximc infarction)
infection Scr 150/rniol/l

9(28. F) 1/86 Cadaver graft CsA + P 32 months Yes Yes No 182 240 200 Amoxyallin No further
GN (US) 34 months Yes Yes No : X - 200 284 210 Amoxyallin recurrence
SCr 200 umol/1
10(20. M) Cholccystectomy; CsA + P + Aza 36 months Yes No Pulmonary 400 530 Amoxytillin+ Lost graft
GN bil nephreclomy; infection Ciprofloxadn within 1 month
sptcncctomv;
1/86 cadaver graft (US);
chronic rejection
II (36. M) 9/86 Living non- CsA + P+Aza 3 months Yes No No 150 160 160 Amoxycfllin No recurrence,
UA rclated graft (IND) SCr ISOfimol/l
12(16. M) 4/87 Uving rcUted CsA + P 14 month] Ye« No No 142 148 130 Amoxycillin No recurrence
UA graft. (RAFH) SCr 140/nnol/l
13 (SI. M) 8/87 Living related CsA + P 1 week No YCJ No 140 144 138 Amoxyallin No further
UA graft. (RAFH) 6 No Yes No 122 128 116 Amoxycillin episode
34 No Yes No 174 158 142 Cprofloxaan SCr 146/onol/l
14(28. M) 9/87 Living non- ClA Aza 2 weeks Ye» No Dysuna 146 150 150 Amoxyallin No recurrence.
GN rclated graft (IND). SCr 150/imol/l.
15(20. M) 10/87 Living related ClA + P 6 month* Yei No 350 550 ~ Amoxydllin + Lost graft
UA graft (RAFH), chronic Nctilmicin within 1 month.
rejection + Azn,
16(27. M) 5/88 Cidiver grift 3 weeks YCJ No No 96 100 90 Amoxycillin No Recurrence,
ON (RAFH) CiA + P SCr 95/aiiol/1
17(43. M) 6/88 Living non-rdated 5 months Yes Yes No 112 118 116 Amoxydllin F i m manifes-
graft (IND) CJA + P tation of AIDS.
UA
No recurrence,
SCr IIO^mol/1.
18(18. F) 7/88 Cadaver graft CsA + P 5 weeks Yes Yes Pulmonary 80 78 76 Amoxyallin No recurrence,
GN (RAFH) infection SCr 70 fjmol/1.
19(24. F) 6/89 Living related ClA + P 6 weeks No Yes No 88 96 90 Amoxyallin No recurrence
UA graft (RAFH) 13 months No Yes No 76 80 72 Ciprofloxacin SCr 68 fimol/1.
20 (26. F) 8/89 Cadaver graft ClA + P 132 140 128 Amoxyallin No recurrence
GN (RAFH) Scr 130 umol/1

GN, glomcruloncphrius, UA. unknown aetiology; IN, interstitial nephritis; CsA. cydosporin A, P, prednisolonc. Aza. azathiopnne; RAFH. Riyadh Armed Forces Hosptul. US. United States, IND. India
Patients Numbered* Additional Factors
1.3. 9. 17 HBiAg-positivc
HBeAg-positive
1.2.3.9. 17 Chronic liver disease
6,9. 13. 15. 16, 17.20 Antacids
9. II. 13. 15. 16. 19.20 On ranitidine
2 Steroid-induced diabetes
9 Sickle cell trait
13 Previous gastric surgery
 Non-typhoid Salmonella in Renal Transplant Recipients 239
//mol/1 {Patient 10). Patients 6 and 12 had stable good renal function with serum creatinine

Immunosuppression consisted of a combination of cyclosporin A and prednisolone in

13 patients and triple therapy in six, one of whom was changed to cyclophosphamide when
chronic liver disease was diagnosed. Only one patient was receiving azathioprine and
prednisolone. The mean prednisolone dose of the entire group was 16.6 mg/day (range
5-30 mg). The early presenters were on a mean prednisolone dose of 20.8 mg per day (range
20-30 mg) compared to late presenters, who were on a mean dose of 8.3 mg per day (range 5-10
mg). The mean daily dose of azathioprine was 64 mg (range 50-100 mg). The mean whole blood
cyclosporin A level of the entire group, determined by radioimmunoassay, was 494 ng/ml
(range 100-774 ng/ml).
There were 31 episodes of non-typhoid Salmonella infection in 20 patients. Seven (35 per
cent) had recurrent episodes (three in three patients and two in four) and 13 patients had
single infections. Patient 13 had three episodes with two different serotypes of the bacterium.
The most common presentation was fever (temperature > 38.5°) in 24 (77 per cent)
episodes, which was associated with diarrhoea in only 11. Fever was the only manifestation
in seven episodes, associated with pyelonephritis and pulmonary infection in three episodes
each, and septic arthritis of the shoulder joint in two episodes. One episode was associated
with metastatic abscesses, and one with extensive Kaposi's sarcoma. Blood cultures were
positive in 15 (62.5 per cent) of these 24 episodes and were the only source of organisms in
nine. In the other patients, bacteria were also isolated from stool, urine, synovial fluid and
pus. In 16 episodes, the organisms were isolated from urine, stool or both. Diarrhoea was
present in 18 instances, with fever as the most common accompanying symptom. It was the
only symptom in seven (22.6 percent) episodes, in which the bacterium was isolated from the
stools alone. Urinary salmonellosis alone was the initial manifestation in three patients, none
of whom had had previous surgery or a structural abnormality of their urinary tract apart
from the transplant operation. These episodes occurred within two weeks post-transplan-
tation in two patients and within six months in the third.
The organisms isolated in the whole group of patients belonged to groups B, C, D and E
according to the Kauffmann-White scheme [34] (Table 2). Two patients with urinary
salmonellosis were infected by organisms of group B, and one group D. Further
identification of the species is not available in our hospital. All these isolates were sensitive to
amoxycillin.
All patients were treated with amoxycillin (1 g q.d.s.) for six weeks for the first episode and
12 weeks for recurrences, except for Patients 13 and 19 who received ciprofloxacin

TABLE 2. Distribution of non-typhoid salmonellosis

by Kauffmann- White scheme [34]

Patient numbers Group Number of episodes

3", 4, 14, 15 B 6
l,2',6,8 b , 10, ll,13 b , 19" C 13
5', 7, 12, 13, 16, 17, 20 D 9
9», 18 E 3

Patient number 13 had three episodes of diarrhoeal

illness due to two different groups of non-typhoid Salmo-
nella
•Three episodes
b
Two episodes
240 JM Dhar and others
monotherapy (750 mgBD) for four weeks for recurrence. Seriously ill patients also received
additional cefotaxime, and aminoglycoside or ciprofloxacin for the first 7-10 days.
Patients 7,14, and 15 who had single episodes of infection, had received preceding pulse
methylprednisolone (0.5 g i.v. for three days). No patient was leukopenic or had a recent
cytomegalovirus infection.
Repeated episodes were observed in seven patients and were recurrences caused by the
same organism in all except one episode in Patient 13. Three patients had two recurrences
and four had one recurrence. These occurred within one week to three months after
discontinuation of antibiotic therapy in all except four, when it occurred after seven months
to two and a half years. In this group, no reservoir of infection was found in the biliary and
urinary systems and none had a vascular or other prosthesis. The presentation of subsequent
episodes of non-typhoid salmonellosis was identical during eight episodes; in the rest there
were additional features of either fever, diarrhoea, or respiratory infection.
Three of the four HIV-positive patients remain well without AIDS after a mean
observation period of four years (these are part of a report presented earlier [35]). Two have a
stable functioning transplant and the third is on haemodialysis. In the fourth patient, non-
typhoid salmonellosis was the first manifestation of clinical AIDS six months post-
transplantation.
Four patients lost their grafts (Patients 4, 7, 10 and 15). In two patients with chronic
rejection and slow decline in graft function with a serum creatinine of 350-400 /imol/1, non-
typhoid Salmonella was probably responsible for an accelerated decline in renal function
requiring dialysis within one month of infection. None of these patients had recurrences. In
the other two patients, graft loss was due to unrelated causes: one who had antibody to HIV
had primary non-function due to acute cellular and humoral rejection and the other had
extensive Kaposi's sarcoma necessitating discontinuation of immunosuppression [36].
The mean observation period of 15 patients who had a functioning graft after the first
episode of non-typhoid salmonellosis was 27 months (range 12-61 months) and the final
carriage rate was zero.
One patient with multiple abscesses died from septicaemia and disseminated intravascular
coagulation during the course of non-typhoid salmonellosis. Three other patients died with
stable graft function from unrelated causes.

DISCUSSION
A total of 58 cases of non-typhoid salmonellosis in renal transplant recipients has been
reported in the literature, and we report the largest series of 20 cases, representing an
incidence of 3.4 per cent in our renal transplant population. This makes a total of 78 reported
cases of this infection in renal transplant recipients in the literature.

Incidence (Table 3)
The reported incidence of non-typhoid salmonellosis in this patient population varies from
none [37-39] to 3.9 per cent [18, 20-31] and one series reported an incidence of 9.5 per cent
[19]. The incidence is higher in tropical than subtropical regions. In the USA the annual
incidence of non-typhoid Salmonella infection in the renal transplant population [18, 22] is
20 times that in the normal adult population [17, 40]. The figures for the normal adult
population in Saudi Arabia are not available for comparison but are probably higher than
those in USA.
The incidence of non-typhoid salmonellosis in our renal transplant population may be an
 Non-typhoid Salmonella in Renal Transplant Recipients 241

T A B L E 3. Non-typhoid Salmonella cases in renal transplant recipients reported in literature

Authors Year Country Total Infectious NTS Incidence

[ReH number episodes cases (%)
transplanted (followed reported
up)

Eickhoffef al. [37] 1972 USA 216 404 0 0

Peterson et al. [38] 1982 USA 164 205 0 0
Masur et al. [39] 1982 USA 99 84 0 0
(6 months)
Anderson et al. [18] 1973 USA 216 — 1 0.46
Hau et al. [22] 1978 USA 686 — 1 0.15
Smith et al. [23] 1981 USA — — 1 —
Bruns et al. [28] 1987 NZ — — 1 —
Kessler et al. [29] 1988 France 238 — 1 0.42
Zumla et al. [32] 1988 UK — — 1 —
Peces et al. [25] 1985 Spain — — 2 —
Nielsen et al. [21] 1977 Denmark 291 121 3 1.03
(6 months)
Mussche et al. [20] 1975 Belgium 128 — 5 3.90
Samra et al. [26] 1986 Israel 237 — 5 2.10
Ocharan-Corcuera 1987 Spain 133 — 5 3.75
et al [27]
Panjwani et al. [30] 1988 Kuwait 339 — 5 1.47
Gueco et al. [31] 1988 Philippines 440 — 5 1.14
Berk et al. [24] 1984 South Africa 416 — 8 1.96
Dupuis et al. [19] 1974 Belgium 146 — 14 9.75
Dhar et al. 1990 Saudi Arabia 592 — 20 3.37

underestimate, since 43 per cent of our patients were studied abroad during the time when
they are at the highest risk of infection. However, the incidence of 3.8 per cent in our patients
transplanted in India is not different than the incidence of 4.0 per cent in those transplanted
in the USA, even though the patients from India come back earlier (2-4 weeks) post-
transplant compared to those from USA (six months to one year). None of our follow up
patients had documented infection by non-typhoid Salmonella while being treated abroad.
During the study period, the annual incidence and severity of non-typhoid salmonellosis in
our transplant population declined. Similar observations have been made regarding other
infections in transplant patients [38, 39], partly related to the use of cyclosporin A and lower
doses of prednisolone [38, 39, 41]. There was no outbreak of non-typhoid salmonellosis in
these patients such as that reported in patients on haemodialysis [42], as standard isolation
techniques were routinely employed.

Clinical Features
Age, and sex were clearly stated for 47 patients reported in the literature. Combining our
data in 20 patients, there were 50 males and 17 females with a mean age of 33 years (range 4-
63). Fifty-one transplants were cadaveric and 15 from living donors.

Time of Infection
The patients can be divided into two groups of early presenters ( < 6 months) and late
presenters ( > 6 months): over 70 per cent of patients in our series were early presenters
242 JM Dhar and others
whereas in the literature, where timing of infection is clearly stated, 51 per cent were early
presenters.

Immunosuppression
Early presenters are heavily immunosuppressed and often receive anti-rejection therapy.
Fifteen per cent of our series and 25 percent of patients in the literature first presented after
recent anti-rejection therapy. The mean daily dose of prednisolone at the time of infection in
those reported in the literature was 32 mg (range 20-100 mg). The patients in our series were
on a lower dose of prednisolone, with a mean daily dose of 16.6 mg (range 5-30 mg). None of
the patients in our series had cyclosporin levels in the toxic range.

Clinical Course (Table 4)

The clinical course of non-typhoid Salmonella infection in renal transplant recipients is
different from that seen in immunocompetent patients, where Salmonella may produce
asymptomatic infection of the intestinal tract or have different clinical manifestations. These
may occur individually, simultaneously or consecutively in the course of infection.

Bacteraemic Illness. The most common mode of presentation was febrile illness with positive
evidence of bacteraemia, both in our series and in the literature. Higher incidences of
septicaemia have been reported in patients with malignant disorders [6-9] and AIDS [11-17].

Urinary Tract Infection. The urinary tract was infected less often in our series than in the
cases reported in the literature. In our series, pylonephritis was noted in two patients and one
had bacteriuria before bacteraemia. In previous reports, bacteriuria in 13 renal transplant
recipients persisted for longer than three months, and lasted for nearly one year in two
patients. Nine patients had bacteriuria prior to the bacteraemic episode; pyelonephritis or
perinephric abscess alone or together were noted in six patients. Dupuis et al. reported

TABLE 4. Clinical features of non-typhoid salmonellosis

Features Immunocompetent Renal transplant recipients

Literature Present series
Total number 58 20
Febrile 78% 77%
Bacteraemic 8-8% (1) 60% 63%
Enteritis 68.3% (1) 48% 58%
Urinary tract Invol. 39% 15%
Focal Manifestation 7.4% (1) 33% 25%
2.0% (2)
Recurrence — 0,2) 38% 35%
- one 21% 20%
- two or more 17% 15%
Graft loss 10% 10%
Mortality 4.1% (1) 10% 5%
 Non-typhoid Salmonella in Renal Transplant Recipients 243
negative cultures of kidney specimens obtained in four cases [19]. Infection of the native
kidneys with non-typhoid Salmonella has been reported [19, 34]. Gueco et al. reported a
patient with bacteriuria who, despite seemingly adequate treatment, had a complicated
course following relapse, necessitating cholecystectomy, transplant nephrectomy and
cefotaxime therapy [31]. Bruns et al. (28] reported a patient who had three recurrences of
urinary salmonellosis with sacral and perianal abscesses and acute renal failure within four
days to three weeks of stopping courses of amoxycillin for three to four weeks.

Gastroenteritis. Gastroenteritis was present with equal frequency in our series and in the
literature, but less often than in the immunocompetent host. None of the patients in our
series or reported in the literature became chronic carriers.

Focal Manifestations
Focal manifestations of non-typhoid salmonellosis are more frequent among renal
transplant recipients than in patients without underlying disease. They included multiple
abscesses, septic arthritis and pulmonary infection in our series. Focal manifestations
reported in the literature have included vascular infections, including infections of saccular
aneurysm [23], pseudoaneurysm in the arterial stump of the transplanted kidney [27],
vascular grafts [29], arteriovenous fistula [26] and septic axillary phlebitis [26]; pulmonary
infections, including pneumonia [24, 25], lung abscess [24, 29] and septic pulmonary emboli
[24] and infections of the other sites, such as soft tissue abscesses [26], sacral and perianal
abscesses [28], infected intravenous injection site [26], dental abscess [21], maxillary sinusitis
[21], meningitis [20], arthritis [20,25], cholecystitis [31], lymphocoele infection [25], loculated
fluid in the abdomen [31], and peritonitis [22, 25]. Localization in the genitourinary system
has been reported as orchitis [19, 20], prostatitis [31] and perinephric abscess [20, 24, 25].

Recurrence
Recurrence of non-typhoid salmonellosis was common in our series and occurred with an
equal frequency in the reviewed literature; recurrence occurred within a week to two years
and nine months after stopping antibiotics. The recurrence of non-typhoid salmonellosis has
been reported in patients with defective immunity [10], including AIDS [13-17]. It was not,
however, noted in two large reviews on salmonellosis in immunocompetent patients [1, 2].
The high rate of recurrence is caused by a latent focus of infection, difficulty in eradicating
the bacterium, inadequate treatment, or conditions further impairing the host's immune
response. Localization of non-typhoid Salmonella in artificial structures or deep-seated
infection, e.g. vascular grafts, aneurysms, haemodialysis fistula, testis, prostrate, joints was
particularly difficult to eradicate and subject to recurrences. We recommend that patients
with recurrences should have their biliary and urinary systems investigated by ultrasonogra-
phy, cholecystography, duodenal aspiration for culture, and intravenous urography; those
with a vascular prosthesis should have a CAT-scan with contrast and/or angiography.

Predisposing Factors
Urinary salmonellosis occurs in patients with structural abnormalities of the urinary tract
due to Schistosoma haematobium infection [43-45], urinary tuberculosis [46], stone disease
[46], cyst [47] and tumours [48]. In these patients, non-typhoid Salmonella bacteriuria has
been associated with recurrent bacteraemic episodes [45]. None of our patients had evidence
244 JM Dhar and others
of stone disease or bilharziases in their remaining native urinary system and only one had
had treated tuberculosis. Patients with recurrent infection of the urinary system had no
abnormalities demonstrated in the urinary tracts of their transplant. Dupuis et al. [19]
reported urinary stasis on excretory urograms of transplanted kidneys in three of their seven
patients with recurrent urinary salmonellosis, but in all cases, the graft was damaged from
previous rejection episodes. Structural abnormalities of the urinary tract should be corrected
if present [48]. Berk et al. [24] suggested bilateral nephrectomy prior to transplantation in
urinary Salmonella carriers.
One of our patients with HIV antibody {Patient 17) had non-typhoid salmonellosis as the
first manifestation of AIDS: this has also been the experience of others [11, 12, 14, 17].
Another patient with HIV antibody continued to have intermittently positive urine and stool
cultures for eight months after his second recurrence, despite adequate antibiotic therapy. A
similar course has been reported in a patient with AIDS [13], and in two HFV-negative renal
transplant recipients [19, 25]. In one, bacterial excretion subsided with the delayed
disappearance of cytomegalovirus-specific IgM antibody [25], and it was concluded that
cytomegalovirus infection may have predisposed to chronic gastrointestinal and urinary
carriage of non-typhoid Salmonella. We had no evidence of recent cytomegalovirus infection
in any of our patients and this has also not been reported by others. However, infection with
HIV may have prolonged urinary and enteric carriage in one of our patients. This
association has not been previously reported in renal transplant recipients. Prolonged
urinary carriage has also been reported with other conditions causing impaired immune
response, including lymphosarcoma [49] and systemic lupus erythematosus [50]. We have
similar experience with three of our patients with systemic lupus erythematosus who were
receiving steroids and azathioprine.
It is interesting to note that 45 per cent of our patients with non-typhoid salmonellosis
were receiving H2-receptor blocking agents or antacids, compared to approximately 25 per
cent of the total transplant population, and one patient had a partial gastrectomy. Gastric
juice is bactericidal for a number of organisms that infect by the oral route [51]. Salmonella
typhimuriwn is killed instantaneously at pH 2 or less, and somewhat more slowly at pH 2-3
[52]. Thus the altered gastric acidity produced by these agents might have influenced
susceptibility to non-typhoid salmonellosis.

Effect on Graft Function

Our series suggests that non-typhoid Salmonella septicaemia accelerates the decline in
already poor graft function, as shown in both of our patients with chronic rejection and
relatively stable serum creatinine of 350-400 jimol/1, both of whom required permanent
haemodialysis within one month of salmonellosis. In other patients there was no permanent
adverse effect on graft function. Infection by non-typhoid Salmonella contributed to
rejection and graft loss of 10 per cent in our series, and a similar figure was seen in the
reported literature, where it has been reported in six patients [19,20, 26, 31]. Previous reports
have associated other bacterial infections with graft rejection [53-55].

Aetiology
Several factors may explain the severity of non-typhoid Salmonella infection in these
patients. Salmonella is an organism that can live intracellularly for long periods, despite the
presence of humoral antibodies and antibiotics [56, 57]. The importance of cell-mediated
immunity in clearing Salmonella has been shown in the mouse [58, 59], and the dose required
 Non-typhoid Salmonella in Renal Transplant Recipients 245
to cause infection is small in immunosuppressed patients [60]. In man, salmonellosis is
unusually severe in patients with impaired T-cell function. Cyclosporin, currently the
mainstay of immunosuppression in renal transplantation, acts by abrogation of the
production of interleukin-2 and a series of other lymphokines secreted by activated T cells
[41, 61]. The further recruitment of cytotoxic T cells is arrested by blocking interleukin-2
synthesis, and inflammatory effector mechanisms diminish in the absence of other
lymphokines, such as macrophage-activating factor, interferons, and colony stimulating
factors [61-64]. Interferon protects against experimental Salmonella typhimurium infection
in the mouse [65].

Source of Persistent Infection

We were unable to demonstrate sources of persistent infection, in common with the
experience of others [21,25-27]. However, Berk et al. [24] found a source of infection in one
of their patients, both of whose original kidneys as well as the transplanted kidney were
infected; this patient excreted non-typhoid Salmonella whilst on haemodialysis. The
presence of a vascular anomaly should be considered as a favourable local condition because
of the vascular tropism of this organism, particularly in devitalized areas [66], and early
surgical intervention is indicated for these patients [67, 68]. Furthermore, non-typhoid
Salmonella may be sequestered within macrophages of the reticuloendothelial system [69],
biliary calculi [70], colonic diverticula [71], chronically inflamed jejunum [72] or lymph node
and spleen [73] where it may be difficult to eradicate them.

Mortality
The mortality in our series (5 per cent) was half that previously reported in renal transplant
recipients and occurred in a patient who had a bacteraemic illness with major focal
manifestations (metastatic abscesses). In the reviewed literature, mortality has been due to
meningitis and perinephric abscess [20], peritonitis [22], cellulitis of the leg and an infected
haemodialysis fistula [26], infection of the vascular prosthesis and lung abscess [29],
cholecystitis, moniliasis, gastrointestinal bleeding and hepatic encephalopathy [31], loca-
lized peritonitis and hepatic failure [31]. Three other patients died due to intercurrent fungal
infection during or shortly after non-typhoid salmonellosis [19, 31]. Thus a bacteraemic
illness with major focal manifestations is an adverse prognostic feature with regard to
morbidity and mortality and warrants vigorous treatment for a prolonged period.

Serotype
In the reported literature Salmonella typhimurium, which belongs to group B of the
Kauffmann-White scheme for serological classification of Salmonella [34], was the most
common serotype (57 per cent) responsible for non-typhoid salmonellosis. We however, did
not find it to be the chief pathogen.

Treatment
Amoxycillin in a dose of 1 g q.d.s. for six weeks was used successfully in all except deep-
seated infections or when additional factors further suppressing immunity were present,
when it was continued for a prolonged period of three months or more. Recently,
ciprofloxacin has been used successfully, and ampicillin was also effective [20, 21, 26]. Only
246 JM Dhar and others
two cases of ampicillin resistance have been described in renal transplant recipients [23, 26],
one having primary resistance and the other developing resistance during the course of
therapy. Antiobiotic resistance in Salmonella species is not uncommon [74], however, in a
study of antibiotic resistance pattern of 1015 salmonellae isolated over a three-year period at
our hospital, Bakheshwein and Osoba (unpublished observations) found only 2.5 per cent to
be resistant to ampicillin, compared to 5.4 per cent resistant to cotrimoxazole, 4.4 per cent to
chloreamphenicol and 1.2 per cent to both ampicillin and cotrimoxazole. Similar
observations were made by Kassimi and Gosling from Jeddah in Saudi Arabia [75]. Berk et
al. [24] suggested that chloramphenicol is the drug of choice. However, there is a danger of its
producing marrow aplasia, especially when used in addition to azathioprine [19, 76], and it
may not eradicate non-typhoid Salmonella from intravascular sites [77]. Cotrimoxazole is an
alternative effective drug, although it may cause a reversible rise in serum creatinine when
used with cyclosporin A [78, 79].
There is increasing evidence that ciprofloxacin (quinolone antibacterial agent) is highly
effective in the treatment of salmonellosis [80, 81] and it has an important role in the
treatment. It has also been found to be effective in the treatment of multi-resistant strains
[82], chronic carriers [83, 84], recurrences [32, 85], penicillin and other drug allergy [80],
immunocompromised patients with AIDS [91] and renal transplant recipients [28, 32], and
our initial experience is encouraging. It is well absorbed with few adverse effects in adults and
is excreted in bile, mucous, urine in high concentration; it penetrates soft tissues, bone and
meninges well [80, 82, 86] and kills non-typhoid Salmonella residing inside macrophages
without altering intestinal flora [83, 86], preventing development of a carrier state [86]. There
is in vitro evidence to suggest that clinical resistance is much less likely to occur than with
other major groups of antimicrobials [87]. Dosage reduction to half is required only when
creatinine clearance is less than 20-30 ml/min [88]: a dose of 750 mg twice daily for four
weeks is probably appropriate for immunocompromised renal transplant recipients,
including carriers, as shorter courses can lead to recurrence [32, 83].
Other effective drugs include the newer cephalosporins and aminoglycosides. The choice
of initial antibiotic therapy should depend on the local sensitivity pattern of the non-typhoid
Salmonella and should be changed as required, depending upon the sensitivity of the
particular organism causing infection. There is almost universal agreement that a long
course of antibiotic treatment should be given [ 19-21, 24, 25, 32], though a two-week course
of cotrimoxazole has been effective [27], but not confirmed by others [26, 31].
In view of recent evidence, chronic carriers should be treated with ciprofloxacin [83, 84]
rather than by traditional therapy, such as high-dose amoxycillin (8-12 g) for 6 weeks [89]. If
this fails, cholecystectomy for enteric carriers, or bilateral nephrectomy for renal trans-
planted patients who are urinary carriers, especially those with structural abnormalities,
should be considered.
It is our policy to screen all renal transplant recipients and prospective donors for any
evidence of urinary or intestinal carriage and treat them with amoxycillin and recently with
ciprofloxacin before surgery. We have treated four recipients and five donors with this
protocol without any recurrence post-transplantation.

RECOMMENDATIONS

1. In the pre-transplant evaluation, all potential renal transplant recipients and donors
should be screened for non-typhoid Salmonella and treated if cultures are positive.
Surgery should be considered for chronic carriers.
 Non-typhoid Salmonella in Renal Transplant Recipients 247

2. Non-typhoid salmonellosis should be considered in any patient with a febrile illness

especially with enteritis or localized suppurative infection even at unusual sites.
3. All patients with non-typhoid salmonellosis should be managed so as to prevent patient
to patient spread.
4. All patients infected with non-typhoid Salmonella should have a six-week course of
appropriate antibiotic e.g. amoxycillin for the first episode and 12 weeks or more for
recurrent or focal manifestations. Shorter course of therapy with ciprofloxacin may be
adequate. Surgery is indicated in those with infection of a vascular prosthesis or focal
suppuration.
5. Regular follow up urine and stool cultures should be obtained to detect recurrence/carrier
state employing enrichment and selective media.
6. Those with recurrence should be investigated for evidence of latent infection.

ACKNOWLEDGEMENT
The authors wish to thank Rajat, Jai, Rajni Dhar and Anne Allen for their help in
preparation of this manuscript.

REFERENCES
1. Saphra I, Winter JW. Clinical manifestations of salmonellosis in man. An evaluation of 7779
human infections identified at the New York Salmonella Centre. N Engl J Med 1957; 256: 1128-
1134.
2. MacCready RA, Reardon JP, Saphra I. Salmonellosis in Massachusetts: a sixteen year experience.
N Engl J Med 1957; 256: 1121-1128.
3. Eisenberg GM, Palazzolo AJ, Flippen HF. Clinical and microbiologic aspects of salmonellosis. A
study of 95 cases in adults and children. New Engl J Med 1955; 253: 90-94.
4. Nelson JD, Kusmiesz H, Jackson LH. Treatment of Salmonella gastroenteritis with ampicillin,
amoxycillin or placebo. Paediatrics 1980; 65: 1123-1130.
5. Chalker RB. A review of human salmonellosis. Rev Infect Dis 1988; 10: 111-124.
6. Han T, Sokal JE, Neter E. Salmonellosis in disseminated malignant diseases. A seven year review
(1959-1965). N Engl J Med 1967; 276: 1045-1052.
7. Heineman HS, Jansen WN, Cooper WM, Braude AI. Hodgkin's disease and Salmonella
typhimurium infections. JAMA 1964; 188: 632-634.
8. Sinkovics JG, Smith JP. Salmonellosis complicating neoplastic diseases. Cancer 1969; 24:631 -636.
9. Wolfe MS, Armstrong D, Louria DB, Blevins A. Salmonellosis in patients with neoplastic disease.
A review of 100 episodes at Memorial Centre Over a thirteen year period. Arch Intern Med 1971;
128: 546-554.
10. Cherubin CE, Neu HC, Imperato PJ, Harvey RP, Bellen N. Septicemia with non-typhoid
Salmonella. Medicine 1974; 53: 365-376.
11. Clumeck N, Mascart-Lemone F, Demaubeuge J, Brenez D, Marcelis L. Acquired immune
deficiency syndrome in Black Africans. Lancet 1983; 1: 642.
12. Bottone EJ, Wormser GP, Duncanson FP. Non typhoidal Salmonella bacteremia as an early
infection in the acquired immunodeficiency syndrome. Diagn Microbiol Infect Dis 1984; 2: 247-
250.
13. Jacobs JL, Gold JWM, Murray HW, Roberts RB, Armstrong D. Salmonella infections in patients
with the acquired immunodeficiency syndrome. Ann Intern Med 1985; 102: 186-188.
14. Glaser JB, Morton-Kute L, Berger SR, et at. Recurrent Salmonella typhimurium bacteremia
associated with the acquired immunodeficiency syndrome. Ann Intern Med 1985; 102: 189-193.
15. Smith PD, Macher AM, Bookman MA, et al. Salmonella typhimurium enteritis and bacteremia in
the acquired immunodeficiency syndrome. Ann Intern Med 1985; 102: 207-208.
16. Fischl MA, Dickinson GM, Sinave C, Pitchenik AE, Cleary TJ. Salmonella bacteremia as
manifestation of acquired immunodeficiency syndrome. Arch Intern Med 1986; 146: 113-115.
17. Celum CL, Chaisson RE, Rutherford GW, Barnhart JL, Echenberg DF. Incidence of
salmonellosis in patients with AIDS. J Infect Dis 1987; 156: 998-1002.
248 JM Dhar and others
18. Anderson RJ, Schafer LA, Olin DB. Septicemia in renal transplant recipients. Arch Surg 1973;
106: 692-694.
19. Dupuis F, Vereerstraeten P, Geertruyden JV, Kinnaert P, Schoutens E, Toussaint C. Salmonella
typhimurium urinary infection after kidney transplantation. Report of seven cases. Clin Nephrol
1974:2: 131-135.
20. Mussche MM, Lameire NH, Ringoir SMG. Salmonella typhimurium infections in renal transplant
patients. Report of five cases. Nephron 1975; 15: 143-150.
21. Nielsen HE, Korsager B. Bacteremia after renal transplantation. Scand J Infect Dis 1977; 9: 111-
117.
22. Hau T, Van Hook EJ, Simmons RL, Najarian JS. Prognostic factors of peritoneal infections in
transplant patients. Surgery 1978; 84: 403-415.
23. Smith EJ, Milligan SL, Filo RS. Salmonella mycotic aneurysm after renal transplantation. South
Med J 1981; 74: 1399-1401.
24. Berk MR, Meyers AM, Cassal W, Botha JR, Myburgh JA. Non-typhoid Salmonella infections
after renal transplantation. A serious clinical problem. Nephron 1984; 37: 186-189.
25. Peces R, Fernandez F, Perez F, de Diego I. Salmonella enteritidis infection in renal transplant
recipients. Nephron 1985; 41: 122-123.
26. Samra Y, Shaked Y, Maier MK. Non-typhoid salmonellosis in renal transplant recipients. Report
of five cases and review of the literature. Rev Infect Dis 1986; 8: 431-439.
27. Ocharan-Corcuvera J, Montejo-Baranda M, Lampreabe-Gaztelu I, Aquirre-Errash C. Non-
typhoid Salmonella infection after renal transplantation. Transplantation 1987; 44: 150-151.
28. Burns BJ, Wallace MR. Treatment of Salmonella typhimurium infection in a renal transplant
patient with ciprofloxacin. NZ Med J 1987; 100: 190-191.
29. Kessler M, Gamberoni J, Renoult E. Non-typhoid salmonellosis in renal transplant patients.
Report of a case with colonization of a vascular prosthesis. Nephron 1988; 48: 234.
30. Panjwani DD, Kalawi M, Kumar MSA, Elhag K, Araj G, Abouna GM. Septicemia in renal
transplant recipients: epidemiology and prognosis. Transplant Proc 1989; 21: 2112-2113.
31. Gueco I, Saniel M, Mendoza M, Alano F, Ona E. Tropical infections after renal transplantation.
Transplant Proc 1989; 21: 2105-2107.
32. Zumla A, Lewis D, Brown J. Ciprofloxacin treatment of recurrent Salmonella typhimurium
septicaemia in a splenectomized and immunosuppressed patient. J Antimicrob Chemother 1988;
21:809-810.
33. Al-Hasani MK, Saltissi D, Chang R, Goor HV, Tegzess Am. Successful regrafting of an explanted
transplanted kidney. Transplantation 1987; 43: 916-917.
34. Parker MT, Salmonella. In: Wilson G, Miles A, Parker MT (Eds). Topley and Wilsons Principles
of Bacteriology, Virology and Immunity. 7th Ed. London: Edward Arnold, 1984; 2(37): 332-355.
35. Al-Sulaiman M, Al-Khader AA, Al-Hasani MK, Dhar JM. Impact of HIV infection on dialysis
and renal transplantation. Transplant Proc 1989; 21: 1970-1971.
36. Al-Khader AA, Al-Sulaiman M, Al-Hasani MK, Haleem A. Post-transplant Kaposi sarcoma:
staging as a guide to therapy and prognosis. Nephron 1988; 48: 65.
37. EickhoffTC, Olin DB, Anderson RJ, Schafer LA. Current problems and approaches to diagnosis
of infection in renal transplant recipients. Transplant Proc 1972; 4: 693-697.
38. Peterson PK, Ferguson R, Fryd DS, BalfourHH, RynasiewiczJ, Simmons RL. Infectious diseases
in hospitalized renal transplant recipients: a prospective study of a complex and evolving problem.
Medicine 1982; 61: 360-372.
39. Masur H, Cheigh JS, Stubenbord WT. Infection following renal transplantation: a changing
pattern. Rev Infect Dis 1982; 4: 1208-1219.
40. Bauer H. Growing problem of salmonellosis in modern society. Medicine 1973; 52: 323-330.
41. Kim JH, Perfect JR. Infection and cyclosporine. Rev Infect Dis 1989; 5: 677-690.
42. Lockyer WA, Feinfield DA, Cherubin CE, Carvounis G, Lancu M, Avram MM. An outbreak of
Salmonella enteritis and septicemia in a population of uremic patients. A review of four cases,
including infection of an arteriovenous fistula. Arch Intern Med 1980; 140: 943-945.
43. Miller WS, Floyd TM. Chronic urinary Salmonella carriers. Lancet 1954; 2: 343-344.
44. Hathout SD, El Ghaffar YA, Awny AY, Hassan K. Relationship between urinary schistosomiasis
and chronic enteric urinary carrier state among Egyptians. Am J Trop Med Hyg 1966; 15:156-161.
45. Farid Z, Bassily S, Kent DC, el at. Chronic urinary Salmonella carriers with intermittent
bacteraemia. J Trop Med Hyg 1970; 73: 153-156.
46. Melzer M, Altmann G, Rakowszcyk M, Yosipovitch ZH, Barsilai B. Salmonella infections of the
kidney. J Urol 1965; 94: 23-27.
 Non-typhoid Salmonella in Renal Transplant Recipients 249

47. Barkin RM, Pfister RR, Ashbach NE. Salmonella: an unusual urinary tract pathogen. J Pediatr
1978; 92: 158.
48. Scott MG, Cosgrove MD. Salmonella infection and the genitourinary system. J Urol 1977; 118:
64-68.
49. Han T, Ezdinli EQ, Neter E. Chronic Salmonella bacteriuria complicating lymphosarcoma. Am J
Clin Pathol 1970; 54: 837-838.
50. Frayha RA, Jizi IB, Saadeh G. Salmonella typhimurium bacteriuria: an increased infection rate in
systemic lupus erythematosus. Arch Intern Med 1985; 145: 645-647.
51. Hook EW, Campbell CG. Salmonella osteomyelitis in a patient with sickle cell disease. N Engl J
Med 1957; 257: 403-407.
52. Meynell GG. Some factors affecting resistance of mice to oral infection by Salmonella
typhimurium. Proc Roy Soc Med 1955; 48: 916-918.
53. Byrd LH, Tapia L, Cheigh JS, Aronian J, Stenzel KH, Rubin AL. Association between
Streptococcus faecalis urinary infections and graft rejection in kidney transplantation. Lancet
1978; 2: 1167-1169.
54. First MR, Linnemann CC, Munda R, McConnell CM, Ramundo M, Alexander JW. Transmitted
streptoccal infection and hyperacute rejection. Possible cross-reaction of streptoccal antigens and
antibodies with mammalian tissues. Transplantation 1977; 24: 400-404.
55. Banner B, Makowka L, Demetris A, Tzakis M, Griffin M, Starzl TE. Hyperacute rejection of the
kidney in patients with a negative crossmatch. Transplant Proc 1988; 20: 453-459.
56. Gelzer J, Suter E. The effect of antibody on intracellular parasitism of Salmonella typhimurium in
mononuclear phagocytes in vitro. J Exp Med 1959; 110: 715-727.
57. Hopps HE, Smadel JE. Effect of antibiotics on intracellular Salmonella typhosa. J Immunol 1961;
87: 162-174.
58. Mackeness GB. Resistance to intracellular infection. J Infect Dis 1971; 123: 439-445.
59. Mitsukioshi S, Sato T, Tunaka T. Experimental salmonellosis: intracellular growth of Salmonella
enteritis ingested in mononuclear phagocytes of mice and cellular basis of immunity. J Bacteriol
1961; 81: 863-871.
60. Currey JC. Infecting dose of Salmonella. Lancet 1976; 2: 1296.
61. Cohen DJ, Loertscher R, Rubin MF, Tilney NL, Carpenter CB, Strom TB. Cyclosporine: a new
immunosuppressive agent for organ transplantation. Ann Intern Med 1984; 101: 667-682.
62. Hess AD, Colombani PM. Mechanism of action of cyclosporin: in vitro studies. Cyclosporin Prog.
Allergy 1986; 38: 198-221.
63. Wenger RM, Payne TG, Schreier MH. Cyclosporine: structure-activity relationship and mode of
action. Prog Clin Biochem Med 1986; 3: 176-191.
64. Halloran PF, Urmson J, Farkas S, el al. Effects of cyclosporin on systemic MHC expression.
Evidence that non T-cells produce interferon-gamma in vivo and are inhibitable by cyclosporin.
Transplantation 1988; 46: 68-72.
65. Izadkhan Z, Mandel AD, Sonnenfield G. Effect of treatment of mice with sera containing gamma
interferon on the course of infection with Salmonella typhimurium strain LT-2. J Interferon Res
1980; 1: 137-145.
66. Cohen PS, O'Brien TF, Schoenbaum SC, Medeiros AA. The risk of endothelial infection in adults
with Salmonella bacteremia. Ann Intern Med 1978; 89: 931-932.
67. Finseth F, Abbot WM. One-stage operative therapy for Salmonella mycotic abdominal aortic
aneurysm. Ann Surg 1974; 179: 8-11.
68. Bennett D, Cherry J. Bacterial infection of aortic aneurysms—a clinicopathologic study. Am J
Surg 1976; 113: 321-326.
69. Mackaness GB, Blanden RV. Cellular immunity. Prog Allergy 1967; II: 89-140.
70. Perkins JC, Devetski RL, Dowling HF. Ampicillin in the treatment of Salmonella carriers. Arch
Intern Med 1966; 118: 538-543.
71. Rubenstein AD, Feemster RF, Smith HM. Salmonella as a public health problem in wartime. Am J
Public Health 1944; 34: 841-853.
72. Sprinz H, Gangarosa EJ, Williams M, et al. Histopathology of the upper small intestine in typhoid
fever. Biopsy study of experimental disease in man. Am J Dig Dis 1966; 11: 615-624.
73. Black PH, Kunz LJ, Swartz MN. Salmonellosis: a review of some unusual aspects. N Engl J Med
1960; 262: 811 -817, 864-870, 921 -927.
74. Smith SM, Palumbo PE, Edelson PT. Salmonella strains resistant to multiple antibiotics. Pediatr
Infect Dis 1984; 3: 455-460.
250 JM Dhar and others
75. Kassimi MA, Gosling PJ. Bacterial resistance in western region of Saudi Arabia. J Hosp Infect
1983; 4: 92-93.
76. Case Record. N Engl J Med 1984; 310: 1584-1594.
77. Hornick RB. Non-typhoidal salmonellosis. In: Hoeprich PD, (Eds). A Modern Treatise of
Infectious Processes. 3rd Ed Philadelphia: Harper and Row 1983; p. 655-661.
78. Thompson JF, Chalmers DHK, Hunnisett AGW, Wood RFM, Morris PJ. Nephrotoxicity of
trimethoprim and cotrimoxazole in renal allograft recipients treated with cyclosporin. Transplan-
tation 1983; 36: 204-206.
79. Ringden 0, Myrenfors P, Klintmalm G, Tyden G, Ost L. Nephrotoxicity by cotrimoxazole and
cyclosporin in transplanted patients. Lancet 1984; 1: 1016-1017.
80. Neu CH. Quinolones: a new class of antimicrobial agents with wide potential uses. Med Clin
North Am 1988; 72: 623-636.
81. Stanley PJ, Flegg PJ, Mandal BK, Geddes AM. Open study of ciprofloxacin in enteric fever. J
Antimicrob Chemother. 1989; 23: 789-791.
82. Barnass S, Franklin J, Tabaqchali S. The successful treatment of multi-resistant non-enteric
salmonellosis with seven day oral ciprofloxacin. J Antimicrob Chemother 1990; 25: 299-300.
83. Ferreccio C, Morris JG, Valdivieso C, et al. Efficacy of ciprofloxacin in the treatment of chronic
typhoid carriers. J Infect Dis 1988; 157: 1235-1239.
84. Sammalkorpi K, Landevirta J, Makela T, Rostila T. Treatment of chronic carriers with
ciprofloxacin. Lancet 1987; 2: 164-165.
85. Connolly MJ, Snow MH, Ingham HR. Ciprofloxacin treatment of recurrent Salmonella
typhimurium septicaemia in a patient with acquired immune deficiency syndrome. J Antimicrob
Chemother. 1986; 18: 647-648.
86. Saene RV, Damjanovic V, Williets T. Food handlers and food poisoning. (Letter) Br Med J 1990;
300: 747-748.
87. Smith JT. The mode of action of 4-quinolones and possible mechanisms of resistance. J
Antimicrob Chemother 1986; 18: 21s-30s.
88. Roberts DE, Williams JD. Ciprofloxacin in renal failure. J Antimicrob Chemother 1989; 23: 820-
823.
89. Musher DM, Rubenstein AD. Permanent carriers of non-typhosa salmonellae. Arch Intern Med
1973; 132:869-872.