European Journal of Clinical Microbiology & Infectious Diseases

, Volume 27, Issue 10, pp 969–976

Bloodstream infections among human immunodeficiency virus-infected adult patients: epidemiology and risk factors for mortality

Authors

    • Emergency Department, Hospital Clínic, IDIBAPSUniversity of Barcelona
    • Emergency DepartmentHospital Clínic
  • M. Almela
    • Microbiology Laboratory, Hospital Clínic, IDIBAPSUniversity of Barcelona
  • A. Soriano
    • Department of Infectious Diseases, Hospital Clínic, IDIBAPSUniversity of Barcelona
  • F. Marco
    • Microbiology Laboratory, Hospital Clínic, IDIBAPSUniversity of Barcelona
  • J. A. Martínez
    • Department of Infectious Diseases, Hospital Clínic, IDIBAPSUniversity of Barcelona
  • A. Muñoz
    • Department of Infectious Diseases, Hospital Clínic, IDIBAPSUniversity of Barcelona
  • G. Peñarroja
    • Department of Infectious Diseases, Hospital Clínic, IDIBAPSUniversity of Barcelona
  • J. Mensa
    • Department of Infectious Diseases, Hospital Clínic, IDIBAPSUniversity of Barcelona
Article

DOI: 10.1007/s10096-008-0531-5

Cite this article as:
Ortega, M., Almela, M., Soriano, A. et al. Eur J Clin Microbiol Infect Dis (2008) 27: 969. doi:10.1007/s10096-008-0531-5

Abstract

This study was undertaken to describe the epidemiology and sensitivity pattern of pathogens causing community-acquired (CA) and nosocomial (N) bloodstream infection (BSI) in adult HIV-infected patients and to establish risk factors for mortality. The type of study was a retrospective analysis of BSI episodes prospectively collected through a blood culture surveillance program from January 1991 to December 2006. We used non-conditional logistic regression methods with death as a dependent variable. One thousand and seventy-seven episodes of BSI (6%) occurred in HIV-infected patients out of 16,946 episodes during the period of study. CA and N BSI were 634 (59%) and 443 (41%) respectively. S. pneumoniae and S. aureus were the most frequent pathogens (n = 279, 44%) in CA BSI. Coagulase-negative staphylococci and S. aureus were the most frequent micro-organisms isolated in N cases (n = 169, 38%). Cotrimoxazole resistance was common in CA and N BSI and was caused by gram-negative bacilli (50% and 61% respectively). However, resistance rates to ceftriaxone were low (3%). Crude mortality accounted for 140 cases (13%). The independent risk factors associated with mortality were: liver cirrhosis (OR: 2.90, p = 0.001), corticosteroids treatment (OR: 3.51, p < 0.001), neutropenia (OR: 2.21, p = 0.02), inappropriate empirical therapy (OR: 2.44, p = 0.006), and isolate of C. albicans (OR: 7.58, p = 0.010). BSI in adult HIV-infected patients was often caused by gram-positive pathogens in both CA and N settings. Inappropriate empirical therapy and the presence of other immunosuppressive factors were independent risk factors for mortality. Ceftriaxone could be used as the initial empiric therapy for HIV-infected patients with suspected CA BSI.

Introduction

Bacterial infection is not uncommon in HIV-infected patients, both in community and hospital settings [19]. Bloodstream infection (BSI) is a frequent complication found in HIV-infected patients during bacterial infection and is often associated with a poor prognosis [39], responsible for the immediate cause of death in up to 32% of cases, especially under particular conditions (e.g. intravenous drug abuse, use of a central venous catheter, neutropenia, and a low CD4 T-cell count) [5]. Previous studies have shown variable distributions of organisms causing bacteremia. The most common pathogens described have been Staphylococcus aureus, Streptococcus pneumoniae, and especially Salmonella spp [19]. Many factors may affect the variation, such as the proportion of intravenous drug users in the study population, lifestyles, geographical differences, neutropenia, and prior Pneumocystis carinii pneumonia prophylaxis.

In 1996, protease inhibitors were introduced into the treatment of HIV infection and a substantial change in patient management together with an increase in life expectancy may have affected the epidemiology and the clinical course of BSI in these patients [10].

This study was undertaken to describe the possible changes in epidemiology and the sensitivity pattern of pathogens causing community-acquired (CA) and nosocomial (N) BSI in adult HIV-infected patients throughout the last 16 years divided in two periods (1991–1996 and 1997–2006), to establish risk factors for mortality and hence to give guidance in the choice of empirical antimicrobials.

Patients and methods

Setting

The setting of the study was the Hospital Clínic in Barcelona, Spain. It is a 750-bed university tertiary center that provides specialized and broad medical, surgical, and intensive care for an urban population of 500,000 people.

Study design

The type of study was a retrospective analysis of cases of BSI Bloodstream infection prospectively collected through a blood culture surveillance program from January 1991 to December 2006. For analysis purposes, we have divided the study period into two parts according to the year of introduction of new antiretroviral treatments: 1991–1996 and 1997–2006.

Inclusion criteria

The present study focuses on episodes of significant BSI Bloodstream infection in HIV-infected adult (age > 18 years) patients. They were consecutively enrolled in the study and prospectively followed up until discharged or 30 days after admission.

The antiretroviral treatment and the CD4 count at the moment of BSI Bloodstream infection had been reported irregularly throughout the study period and for this reason we did not include these data in the analysis.

Microbiological methods

Between 1991 and 1997, blood samples were processed by the Bactec NR-730 system (Beckton-Dickinson Microbiology System) and maintained routinely for 7 days. Since 1998 we have used the Bactec system (Beckton-Dickinson Microbiology System), with an incubation period of 5 days. Isolates were identified by standard techniques [11]. Antimicrobial susceptibility testing was performed by a microdilution-automated system (Microscan, Dade Behring, West Sacramento, CA, USA, or Sensititre, Trek Diagnostic Systems, East Grinstead, West Sussex, UK). Antibiotic susceptibility was determined following CLSI guidelines [12]. Micro-organisms reported as intermediate were considered resistant.

Patient characteristics

The following data were obtained for all patients: age, sex, preexisting co-morbidities, prognosis of the underlying disease, prior antibiotic therapy, prior surgery, current administration of > 20 mg of corticosteroids every day, current administration of antineoplastic chemotherapy, source of BSI Bloodstream infection, leukocyte count, origin of the infection (community-acquired or nosocomial, including last conventional hospitalization or outpatient visit), length of hospitalization before diagnosis of bacteremia, ICU admission, need for mechanical ventilation, empirical and definitive antibiotic treatment, susceptibility to antibiotics of the micro-organism isolated, presence of shock, and mortality.

Definition of terms

Significant BSI Bloodstream infection was defined as one or more blood cultures positive for a primary pathogen and clinically apparent signs and symptoms of sepsis (as described previously [13]), with the exception of coagulase-negative staphylococci, Corynebacterium spp, and Lactobacillus spp, which required two separate positive blood cultures with the same antibiogram to be considered a true bacteremia. The source of infection was determined by a senior infectious disease specialist, who considered the patient’s medical history, physical examination, and results of other microbiological tests and complementary imaging exploration. Co-morbidity was defined as a disease or therapy that could predispose patients to infection, alter defense mechanisms, or cause functional impairment, such as the following: diabetes; liver cirrhosis; renal failure; alcoholism (> 100 g of alcohol every day); injecting drug users (IDUs); active neoplastic disease; severe chronic obstructive pulmonary disease; severe cardiac disease with symptomatic heart failure; severe dementia; and administration of immunosuppressive drugs (≥20 mg of corticosteroids every day on a regular basis or antineoplastic chemotherapy). Prior antibiotic therapy was defined as the use of any antimicrobial agent for ≥ 3 days during the month prior to the occurrence of the bacteremic episode. Antibiotic treatment, either empirical or definitive, was considered appropriate if at least one of the antibiotics involved in vitro activity against the bacteria and the dose and route of administration were adequate. Shock was defined as a systolic pressure of < 90 mm Hg that was unresponsive to fluid treatment or required vasoactive drug therapy [13]. Death was considered related to the bloodstream infection if it occurred before the resolution of symptoms or signs or within 7 days of the onset of BSI Bloodstream infection, and if there was no other explanation; otherwise, death was considered unrelated to the episode of BSI Bloodstream infection.

Follow-up

Patients were observed from the diagnosis of BSI Bloodstream infection until 30 days afterward, until death in-hospital or until discharge.

Statistical analysis

Statistical analysis were carried out using the program SPSS (version 13.0; SPSS, Chicago, IL, USA). Continuous variables were expressed as mean and standard deviation (±SD) or median (range) according to their homogeneity. Categorical variables were compared using the X2 test or Fisher’s exact test (when necessary). The quantitative variables were compared using the Student–Fisher t test or ANOVA. Nonparametric tests were used when the application conditions were not applicable. Statistical significance was defined as a two-tailed p value <0.05.

Variables with a p  value ≤ 0.2 in the univariate analysis were further analyzed by use of a stepwise nonconditional (logistic regression) multivariate analysis to find out the independent factors associated with mortality. For analysis purposes, we considered related and unrelated mortality (within 30 days of bloodstream infection) together. Shock (an intermediate variable strongly associated with mortality) was not included [14].

Results

During the 16-year period of the study (1991–2006), there were 16,946 positive blood cultures that were considered true BSI. Out of these, 1,077 (6%) episodes occurred in HIV-infected adult patients. Table 1 shows the chronological distribution of CA and N BSI in this population.
Table 1

Bloodstream infections reported in our hospital from 1991 to 2006 in HIV-infected patients

 

1991–1996

1997–2006

Total

p

Number of true BSI Bloodstream infection in the period of study

5,230

11,716

16,946

 

Number of BSI Bloodstream infection in HIV-infected patients (%)

510 (10)

567 (5)

1,077 (6)

0.001

  Community-acquired (%)

280 (55)

354 (62)

 

0.007

  Nosocomial (%)

230 (45)

213 (38)

  
The epidemiological and clinical characteristics of BSI episodes among HIV-infected patients are shown in Table 2. There were 510 cases in the first period (1991–1996) and 567 in the second period (1997–2006) of study. In the second period of the study the patients were significantly older (42 ± 12 vs 32 ± 11 years, p < 0.001) and the presence of any co-morbidity was significantly higher, with liver cirrhosis being more frequent (18% in 1997–2006). The main source of BSI was unknown in both periods (33% in 1991–1996 and 26% in 1997–2006). Infectious endocarditis was more frequent in the first period (9 vs 5%, p = 0.004) and pneumonia in the second period (20 vs 25%, p = 0.03). Mortality was similar in the two periods: 73 cases (14%) in 1991–1996 and 67 cases (12%) in 1997–2006.
Table 2

Epidemiological and clinical characteristics of BSI Bloodstream infection episodes among HIV-infected patients according to the period of study

Clinical characteristic

1991–1996 (N = 510)

1997–2006 (N = 567)

p

n

%

n

%

Age in years (mean ± SD)

32

± 11

42

± 12

< 0.001

Male gender

394

77

302

53

< 0.001

Co-morbidity

  None

424

83

226

40

< 0.001

  Diabetes mellitus

3

0.6

34

6

< 0.001

  Liver cirrhosis

36

7

102

18

< 0.001

  Chronic renal insufficiency

6

1

41

7

< 0.001

  Chronic lung disease

3

0.6

26

5

< 0.001

  Hematological cancer

28

5

53

9

0.01

  Solid organ cancer

1

0.2

22

4

< 0.001

  Other

9

2

63

11

< 0.001

Previous cotrimoxazol

45

9

74

13

0.01

Corticosteroids

51

10

76

13

0.2

Neutropenia

38

7

43

8

0.4

Previous surgery

6

1

22

4

0.004

Shock

38

8

59

10

0.06

Unknown source

169

33

146

26

0.005

Catheter source

92

18

104

18

0.5

Lung source/pneumonia

103

20

143

25

0.03

Infectious endocarditis

48

9

29

5

0.004

Urinary tract infection

19

4

43

8

0.004

Abdominal source

10

2

19

3

0.1

Crude mortality

73

14

67

12

0.1

Attributable mortality

44

9

53

9

0.4

The microbiological isolates in CA BSI are shown in Table 3. The most frequent isolates were S. pneumoniae and S. aureus in both periods of study (n = 279, 44%). Among gram-negative bacteria Salmonella spp were more frequently isolated in the 1991–1996 period (21% of isolates) than in the second period (10%, p = 0.01). In contrast, E. coli was more frequently isolated in the second period than in the first one (14 vs 7% respectively, p = 0.004). The proportion of oxacillin-resistant S. aureus strains isolated increased to 8% in the 1997–2006 period. The ciprofloxacin resistance in E. coli strains in both periods remained similar (15 and 16% respectively). The cotrimoxazol resistance rate in the CA gram-negative bacilli bacteremia was 50%. However, resistance rates to ceftriaxone were low (3%).
Table 3

Microbiological isolates in community-acquired BSI Bloodstream infection among HIV-infected patients

Microbiological isolates

1991–1996 (N = 280)

1997–2006 (N = 354)

p

n

%

n

%

Gram-positive bacteria

148

53

215

61

0.04

  S. pneumoniae

68

24

107

30

0.06

    Penicillin R

16

24a

14

13a

0.01

  S. aureus

51

18

53

15

0.2

    Oxacillin R

0

4

8a

  Coagulase-negative staphylococci

8

3

18

5

0.2

  S. pyogenes

2

0.7

10

3

0.1

  S. mitis

5

2

5

1

0.2

  S. agalactiae

8

2

  Streptococcus spp

6

2

11

3

0.3

  E. faecalis (and spp)

8

3

3

1

0.1

Gram-negative bacteria

107

38

117

33

0.06

  Salmonella spp

58

21

36

10

0.01

  Enterobacteriaceae

    E. coli

19

7

48

14

0.004

      Ciprofloxacin R

3

16a

7

15a

0.5

    Klebsiella spp

2

1

5

1

0.3

    Enterobacter spp

1

0.4

3

1

0.6

  P. aeruginosa (and spp)

14

5

9

3

0.08

  H. influenzae

7

3

10

3

0.9

  C. jejuni (and spp)

6

2

6

2

0.9

Fungi

21

8

11

3

0.05

  C. neoformans

17

6

7

2

0.3

  C. albicans (and spp)

4

1

4

1

0.6

Other

4

1

11

3

0.5

R, resistance

aThe percentage was calculated out of the total number of particular micro-organism isolates

Microbiological isolates in N BSI are shown in Table 4. The most frequent isolates were gram-positive bacteria, but, in contrast to CA BSI, the micro-organisms more frequently isolated were coagulase-negative staphylococci and S. aureus (n = 169, 38%). The proportion of oxacillin-resistant S. aureus strains was significantly higher in the first period (13 out of 32 strains of S. aureus isolated in 1991–1996 vs 2 out of 16 strains of S. aureus isolated in 1997–2006). Among gram-negative bacteria, P. aeruginosa and E. coli were the micro-organisms more frequently isolated in both periods of study. The ciprofloxacin resistance was significantly higher in the second period than in the first period of study (33 vs 5% respectively, p = 0.002). The cotrimoxazol resistance rate in N BSI caused by gram-negative bacilli was 61%.
Table 4

Microbiological isolates in nosocomial BSI Bloodstream infection among HIV-infected patients

Microbiological isolates

1991–1996 (N = 230)

1997–2006 (N = 213)

p

n

%

n

%

Gram-positive bacteria

130

57

112

53

0.08

  Coagulase-negative staphylococci

56

24

65

31

0.09

  S. aureus

32

14

16

8

0.02

    Oxacillin R

13

41a

2

13a

0.001

  S. pneumoniae

10

4

9

4

0.6

    Penicillin R

1

10a

1

11a

0.5

  E. faecalis (and spp)

19

8

18

8

0.7

  S. mitis

4

2

3

1

0.7

  S. agalactiae

1

0.4

1

0.5

0.8

  Streptococcus spp

8

3

Gram=negative bacteria

72

31

67

31

1

  P. aeruginosa (and spp)

34

14

27

13

0.6

  Enterobacteriaceae

    E. coli

19

8

21

10

0.5

      Ciprofloxacin R

1

5a

7

33a

0.002

    Klebsiella spp

2

1

9

4

0.03

    Enterobacter spp

1

0.4

1

0.5

0.9

  Salmonella spp

15

7

7

3

0.2

  C. jejuni (and spp)

1

0.4

2

1

0.9

Fungi

17

7

15

7

1

  C. albicans (and spp)

15

7

14

7

0.8

  C. neoformans

2

1

1

0.5

0.9

Other

11

5

19

9

0.1

R, resistance

aThe percentage was calculated out of the total number of particular micro-organism isolates

Risk factors associated with mortality

Crude mortality accounted for 140 cases (13%). The clinical and microbiological characteristics associated with death are shown in Tables 5 and 6. In the multivariate analysis (Table 7), the variables independently associated with mortality were liver cirrhosis, previous or current treatment with corticosteroids, the simultaneous presence of neutropenia, the administration of an incorrect empirical antibiotherapy and an isolate of C. albicans in blood cultures. Finally, predictive factors for a BSI caused by C. albicans were: previous antibiotherapy (OR: 3.48, 95%CI: 1.03–11.78) and treatment with corticosteroids (OR: 2.92, 95%CI: 1.09–7.82) with a specificity of 92% and a negative predictive value of 99%.
Table 5

Epidemiological and clinical characteristics associated with mortality in BSI Bloodstream infection among HIV-infected patients

Clinical characteristic

Alive (N = 937; 87%)

Dead (N = 140; 13%)

p

n

%

n

%

Age in years (mean ± SD)

37

±13

38

±12

0.4

Male gender

593

63

103

74

0.01

Co-morbidity

  None

583

62

67

48

0.01

  Diabetes mellitus

31

3

6

4

0.8

  Liver cirrhosis

110

12

28

20

0.01

  Chronic renal insufficiency

41

4

6

4

0.9

  Chronic lung disease

26

3

3

2

0.8

  Hematological cancer

68

7

13

9

0.7

  Solid organ cancer

17

2

6

4

0.7

  Other

61

7

11

8

0.8

Origin of bacteremia

  Community-acquired

573

61

61

44

 

  Nosocomiala

364

39

79

56

<0.001

Period of isolate

     

  1991–1996

437

47

73

52

0.1

  1997–2006

500

53

67

48

 

Previous antibiotic therapy

314

33

64

46

0.07

Previous cotrimoxazole

101

11

18

13

0.8

Corticosteroids

86

9

41

29

<0.001

Neutropenia

54

6

27

19

<0.001

Central venous catheterization

166

18

28

20

0.8

Previous surgery

24

3

4

3

0.9

Fever

910

97

134

96

0.9

Shock

29

3

68

49

<0.001

Inappropriate empirical therapy

516

55

96

69

<0.001

Unknown source

271

29

44

31

0.3

Venous catheter source

179

19

17

10

0.09

Lung source/pneumonia

202

22

44

31

0.08

Infectious endocarditis

67

7

10

7

0.9

Urinary tract infection

60

6

2

1

0.2

Abdominal source

20

2

9

6

0.2

Persistent bacteremia

40

4

4

3

0.8

aNosocomial includes BSI Bloodstream infection acquired during conventional hospitalization and outpatient visit

Table 6

Microbiological isolates associated with mortality in HIV-infected patients with BSI Bloodstream infection

Microbiological isolates

Alive (N=937; 87%)

Dead (N=140; 13%)

p

n

%

n

%

Gram-positive bacteria

534

57

71

50

 

  S. pneumoniae

175

19

19

14

0.5

    Penicillin R

25

14a

7

37a

0.3

  S. aureus

133

14

19

14

0.9

    Oxacillin R

18

14a

1

5a

0.3

  Coagulase-negative staphylococci

132

14

15

11

0.8

  E. faecalis (and spp)

38

4

10

7

0.7

  S. pyogenes

10

1

2

1

0.9

  S. mitis

16

2

1

0.7

0.6

  S. agalactiae

7

0.7

3

2

0.6

  Streptococcus spp

23

2

2

1

0.8

Gram-negative bacteria

316

34

53

38

 

  Salmonella spp

113

12

1

0.7

<0.001

  Enterobacteriaceae

    E. coli

91

10

16

11

0.9

      Ciprofloxacin R

15

16a

3

19a

0.6

    Klebsiella spp

15

2

3

2

0.9

    Enterobacter spp

13

1

1

0.7

0.9

  P. aeruginosa (and spp)

57

6

27

19

<0.001

  H. influenzae

13

1

4

3

0.8

  C. jejuni (and spp)

14

1

1

0.7

0.7

Fungi

48

5

16

11

 

  C. albicans

8

1

9

6

<0.001

  Candida spp

17

2

3

2

0.5

  C. neoformans

23

2

4

3

0.8

Other

39

4

R, resistance

aThe percentage was calculated out of the total number of particular micro-organism isolates

Table 7

Multivariate analysis of risk factors associated with mortality in BSI Bloodstream infection among HIV-infected patients

Characteristic

OR

95% CI

p

Liver cirrhosis

2.90

1.55–5.41

0.001

Corticosteroids

3.51

1.87–6.56

< 0.001

Neutropenia

2.21

1.15–4.23

0.02

Inappropriate empirical therapy

2.44

1.29–4.65

0.006

Candida albicans

7.58

1.61–35.65

0.01

Discussion

Since the beginning of HIV disease, different studies have reported that bacterial infections were common in HIV-infected patients because of abnormalities in humoral, cellular, and mucosal immunity. In addition, HIV-infected patients had an increased risk of bacteremia during bacterial infections [13]. However, according to our results and those of other investigations [10], the incidence of BSI among HIV-infected adult patients has decreased in the 1997–2006 period of study, particularly the nosocomial episodes. This is probably because in 1996, new reverse transcriptase inhibitors were introduced into the treatment of HIV infection, followed shortly thereafter by the protease inhibitors. Since then, a substantial change in patient management together with an increase in life expectancy has been reported [15]. As a consequence of improved survival, HIV-infected patients developed comorbidities as reflected in our results, which showed a population of HIV-infected adult patients with BSI that was older and with higher frequency than any co-morbidity in the 1997–2006 period. With regard to the source of bacteremia, infectious endocarditis was more frequent in the first period of study, probably because of the highest prevalence of active IDUs in the HIV population and pneumonia was more frequent in the second period probably because this reflected an improved immunological status.

Most of the CA bacteremia in the HIV-infected patients was caused by Gram-positive bacteria, similar to results reported by other studies in our setting [10]. Pneumococcal infection incidence may be explained by the prevalence of abnormalities in humoral immunity in these patients. Salmonella enteritidis and S. tiphymurinum were the most common species in gram-negative CA BSI and were identified in 21% cases during the 1991–1996 periods and in 10% episodes throughout the 1997–2006 periods. Of note is the decreased incidence of this particular micro-organism in the second part of the study, probably because of the improvement in the cellular immunity in the HIV population treated with highly active antiretroviral therapy. Something similar might explain the decrease in cryptococcal infection incidence during the second period of study. On the other hand, the incidence of penicillin-resistant S. pneumoniae isolates and methicillin-resistant S. aureus was low in the 1997–2006 period and the amount of ciprofloxacin resistance of E. coli isolates in CA bacteremia was around 15%. Although cotrimoxazole is widely used as prophylaxis for Pneumocystis and Toxoplasma, it may not prevent the occurrence of bacterial infections and bacteremia [16]. In addition, the cotrimoxazole resistance rate in the CA Gram-negative bacilli BSI in our study was 50%. Therefore, we suggest that an initial treatment with ceftriaxone could be an appropriate empirical choice and change the regimen according to returning sensitivity patterns. However, in cases of severe infections with risk of S. aureus etiology, the addition of a glycopeptide should be considered.

In a nosocomial setting, microbiological epidemiology was similar to that of hospital-acquired BSI in the general population [17]. The micro-organisms more frequently isolated were coagulase-negative staphylococci (n = 121, 27%), S. aureus (n = 48, 11%), P. aeruginosa (n = 61, 14%), and E. coli (n = 40, 9%). About the sensitivity pattern, in contrast to that observed in CA BSI, our study reported a lower proportion of oxacillin-resistant S. aureus isolates in the second period than in the first one (13% vs 41%, p = 0.001), the presence of ciprofloxacin-resistant E. coli strains was higher during the 1997–2006 period than the 1991–1996 period (33 vs 5%, p = 0.002) and the isolates of the extended spectrum beta lactamase micro-organism were low (only 4 cases in the second period). Therefore, antibiotherapy with activity against P. aeruginosa and probably methicillin-resistant S. aureus should be used in the empirical treatment of nosocomial primary BSI in HIV-infected patients.

Multivariate analysis identified co-morbidity with liver cirrhosis, concomitant use of corticosteroids, the simultaneous presence of neutropenia, and inappropriate empirical therapy being risk factors for mortality in HIV patients with BSI. It is interesting to note that only C. albicans isolate was independently associated with mortality. Predictive factors for C. albicans isolate were similar to that previously reported [18] and it is important to know them and promptly apply an antifungal treatment in these cases.

There are two main limitations of this study: the antiretroviral treatment and the CD4 count at the moment of BSI episode had been reported irregularly throughout the study period and for this reason we did not include these data in the analysis. There have been many reports revealing a reduction in the incidence and epidemiological changes in bacterial infections after introducing highly active antiretroviral therapy into the HIV population [19, 20]. As we did not have these data at our disposal, we studied the CA and N BSI characteristics according to the year of the isolate divided into two periods, 1991–1996 and 1997–2006, as an indirect estimation of the effect of antiretroviral treatment. We reported that some clinical and microbiological characteristics were significantly different depending on the period of the isolate, but there was no influence on mortality.

In conclusion, BSI in adult HIV-infected patients was often caused by Gram-positive pathogens in both CA and N settings. Ceftriaxone could be used as the initial empiric therapy for HIV-infected patients with suspected CA bacteremia. However, in N cases, antibiotherapy with activity against P. aeruginosa, and probably methicillin-resistant S. aureus, should be used associated with antifungal therapy in cases of previous use of antibiotics or corticosteroids. Co-morbidity with liver cirrhosis, the presence of other immunosuppressive factors (such as corticosteroid use or neutropenia), inappropriate empirical therapy, and C. albicans isolate in blood cultures were independent risk factors for mortality in HIV-infected patients who presented with a BSI. It is important to know the sensitivity pattern of the micro-organisms involved in these cases to guide the most appropriate empirical antibiotherapy in every setting.

Acknowledgements

We are indebted to Dr. J.M. Gatell and Dr. J.M. Mallolas for their help in the study. This work was supported by grants from the Fundación Máximo Soriano Jiménez of Barcelona.

Conflict of interest statement

None

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© Springer-Verlag 2008