Journal of Antimicrobial Chemotherapy (1978) 4 (Suppl. C), 83-90
Bacteraemia
P. Noone, R. L. Abeysundere and J. M. Bradley
'Septic shock' is produced most commonly by Gram-negative bacilli derived from pre-existing infections in various parts of the body. Anaerobic bacteraemic states are most frequently due to Bacteroides fragilis and are usually derived from sepsis in the gastrointestinal or female genital tracts, or from aspiration pneumonia. Among aerobic bacilli, Pseudomonas aeruginosa has emerged as an increasingly frequent cause of septic shock, especially in leukaemic patients. For the treatment of septic shock of unknown cause gentamicin is the drug of first choice; if anaerobes are thought to be implicated metronidazole should be added. The possible presence of Ps. aeruginosa or streptococci requires the addition of carbenicillin or benzylpenicillin respectively. Introduction
Strictly speaking the term 'bacteraemia' covers a multitude of clinical syndromes, from an asymptomatic condition to septic shock. In this paper the word is used synonymously with 'septicaemia', and the concern is primarily with 'septic shock'. Septic shock can be produced by a variety of bacteria but it is associated most frequently with Gram-negative bacilli such as Proteus spp., Escherichia coli, Pseudomonas spp., Klebsiella spp., Acinetobacter spp., and the Bacteroides spp. Staphylococcus aureus can also produce a septic shock syndrome. The pathophysiology of septic shock involves endotoxins reacting with platelets and the complement system to produce vasoactive substances which affect the calibre and permeability of small blood vessels. This leads eventually to peripheral circulatory faiJure and inadequate perfusion of tissues and organs including the brain and kidneys. Septic shock is associated with a high mortality. Clinical manifestations of septic shock include rigors, fever, hypotension (a very important clinical sign), tachycardia, and also oliguria, acute renal failure, confusion, mental disturbance, jaundice and coagulation defects. The incidence of bacteraemia, and especially that due to Gram-negative bacilli has increased over the last 20 to 30 years (McCabe & Jackson, 1962; Du Pont & Spink, 1969; Finland, 1970). Table 1 shows the incidence of bacteraemia at the Royal Free Hospital during the last 5 years, from which an increasing trend is evident. Of the organisms isolated from blood cultures over this period (Table II) isolations oiStaph. aureus and of E. coli have remained the same. Pseudomonas aeruginosa showed an 83 0305-7453/78/O9Ol-CO83$01.0O/0
O 1978 The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 31, 2015
Department of Medical Microbiology, Royal Free Hospital, London NW3 2QG, England
P. Noone, R. L. Abeysundere and J. M. Bradley
84
Table I. The incidence of significant isolates from blood cultures per 1000 admissions (or discharges') during the period 1972-1976 at the Royal Free Hospital No. of blood culture investigations/1000 admissions
Year
116 103 103 170 149
Incidence of bacteraemia/1000 admissions GNRt
Total
2-4 3-3 3-8 5-2 3-2
61 6-5 7-6 7-7 8-0
112 113 123 147 171
60 90 9-8 6-4 7-1
* Figures worked out per 1000 discharges. + Gram-negative rods. Table II. Significant positive blood cultures at the Royal Free Hospital
Staph. aureus Staph. epidermidis E. coli Klebsiells spp. Enterobacter spp. Proteus spp. Ps. aeruginosa Streptococci (Str. pneumoniae) Candida Anaerobes Total
1972
1973
1974
1975
1976
27 7 17 11 3 Nil 3
16 4 22 8 2 5 4
14 6 16 13 5 3 10
24 5 23 18 5 5 9
26 15 21 9 4 6 12
18(5) _ 1 87
23(4) _ 5 84
24(6) _ 6 101
19(4) _ 18 125
38(6) 4 9 150
increase, partly due to increased numbers of patients with leukaemia. Large numbers of streptococci have been isolated, particularly from patients with hepatocellular liver disease. There has been a marked increase in the number of anaerobes isolated—from 1 of 87 (1 • 1 %) in 1972 t o l 8 o f l 2 5 ( 1 4 % ) i n l 975. Although we changed our routine practice in 1972-73 by starting to use Thiol broth, we consider that the decisive factor in the increase in the number of anaerobes isolated was the setting up of an anaerobic section in our laboratory. This development increased our isolation rate of anaerobes not only from blood cultures but also from other specimens generally. We consider that this increased isolation rate is attributable more to the change in awareness and organization of our resources than to simple changes in media employed. Bacteraemia may develop as a complication of a great variety of infections in many different parts of the body. Important predisposing factors include trauma, obstructive lesions, instrumentation, immunosuppression, diabetes and malignant disease.
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 31, 2015
1972 1973 1974 1975 1976*
No. of patients with bacteraemia
% Significant positives cultures
Bacteraemia
85
During the last 40 years increasing numbers of patients with compromised defence mechanisms have been admitted to hospital for active medical and surgical treatment including invasive investigational techniques and therapy which may greatly increase the risks of infection. Special investigations
Table III. Investigations Blood cultures (more than one, including anaerobic) Full blood count (including platelets; buffycoat Gram stain) Urea, electrolytes, creatinine (Blood for serum storage—'antibodies') Urine—microscopy, culture, ward tests Swabs—septic areas; ulcers; i.v. sites; tracheostomy Specimens—drainage fluid; pus; sputum; ascites; dialysis fluid; ends of i.v. cannulae. Additional Tests Screen for fibrin degradation products Blood group and save serum for cross-match Liver function tests CXR (abdo X-rays)] s h o u , d n Q t d e ) a y t r e a t m c n t Blood gases and pH CVP readings
Antibacterial chemotherapy
Antibacterial treatment, although of great importance, is only one part of the total management of bacteraemia. Recommendations for antimicrobial therapy for bacteraemia with adult dosages are summarized in Table IV. Gentamicin is still the first choice in treating shock of unknown bacterial cause, before the results of blood cultures are known. If the source of sepsis is the biliary tract, alimentary tract, female genital tract, gangrenous tissue or an aspiration pneumonia, anaerobes are likely to be implicated and metronidazole or clindamycin should be added. Unfortunately, clindamycin occasionally causes pseudomembranous colitis, while metronidazole has not been recognized as having any major toxicity during short courses of 7 to 10 days. Moreover, it has been shown that clindamycin and lincomycin interfere with the bactericidal action of gentamicin and tobramycin against colifonns (Riff & Matulionis, 1975). This is a phenomenon which has been clinically suspected by the present authors, and is another reason for preferring metronidazole at the present time.
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 31, 2015
The investigations that are usefully undertaken in patients with suspected bacteraemia are summarized in Table III. It is crucial to obtain blood cultures and other specimens for microbial investigation before antibiotics are started.
86
P. Noooe, R. L. Abeysundere and J. M. Bradley
Table IV. Antibiotic chemotherapy
In patients who are neutropoenic (
Bacteraemia
P. Noone, R. L. Abeysundere and J. M. Bradley
'Septic shock' is produced most commonly by Gram-negative bacilli derived from pre-existing infections in various parts of the body. Anaerobic bacteraemic states are most frequently due to Bacteroides fragilis and are usually derived from sepsis in the gastrointestinal or female genital tracts, or from aspiration pneumonia. Among aerobic bacilli, Pseudomonas aeruginosa has emerged as an increasingly frequent cause of septic shock, especially in leukaemic patients. For the treatment of septic shock of unknown cause gentamicin is the drug of first choice; if anaerobes are thought to be implicated metronidazole should be added. The possible presence of Ps. aeruginosa or streptococci requires the addition of carbenicillin or benzylpenicillin respectively. Introduction
Strictly speaking the term 'bacteraemia' covers a multitude of clinical syndromes, from an asymptomatic condition to septic shock. In this paper the word is used synonymously with 'septicaemia', and the concern is primarily with 'septic shock'. Septic shock can be produced by a variety of bacteria but it is associated most frequently with Gram-negative bacilli such as Proteus spp., Escherichia coli, Pseudomonas spp., Klebsiella spp., Acinetobacter spp., and the Bacteroides spp. Staphylococcus aureus can also produce a septic shock syndrome. The pathophysiology of septic shock involves endotoxins reacting with platelets and the complement system to produce vasoactive substances which affect the calibre and permeability of small blood vessels. This leads eventually to peripheral circulatory faiJure and inadequate perfusion of tissues and organs including the brain and kidneys. Septic shock is associated with a high mortality. Clinical manifestations of septic shock include rigors, fever, hypotension (a very important clinical sign), tachycardia, and also oliguria, acute renal failure, confusion, mental disturbance, jaundice and coagulation defects. The incidence of bacteraemia, and especially that due to Gram-negative bacilli has increased over the last 20 to 30 years (McCabe & Jackson, 1962; Du Pont & Spink, 1969; Finland, 1970). Table 1 shows the incidence of bacteraemia at the Royal Free Hospital during the last 5 years, from which an increasing trend is evident. Of the organisms isolated from blood cultures over this period (Table II) isolations oiStaph. aureus and of E. coli have remained the same. Pseudomonas aeruginosa showed an 83 0305-7453/78/O9Ol-CO83$01.0O/0
O 1978 The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 31, 2015
Department of Medical Microbiology, Royal Free Hospital, London NW3 2QG, England
P. Noone, R. L. Abeysundere and J. M. Bradley
84
Table I. The incidence of significant isolates from blood cultures per 1000 admissions (or discharges') during the period 1972-1976 at the Royal Free Hospital No. of blood culture investigations/1000 admissions
Year
116 103 103 170 149
Incidence of bacteraemia/1000 admissions GNRt
Total
2-4 3-3 3-8 5-2 3-2
61 6-5 7-6 7-7 8-0
112 113 123 147 171
60 90 9-8 6-4 7-1
* Figures worked out per 1000 discharges. + Gram-negative rods. Table II. Significant positive blood cultures at the Royal Free Hospital
Staph. aureus Staph. epidermidis E. coli Klebsiells spp. Enterobacter spp. Proteus spp. Ps. aeruginosa Streptococci (Str. pneumoniae) Candida Anaerobes Total
1972
1973
1974
1975
1976
27 7 17 11 3 Nil 3
16 4 22 8 2 5 4
14 6 16 13 5 3 10
24 5 23 18 5 5 9
26 15 21 9 4 6 12
18(5) _ 1 87
23(4) _ 5 84
24(6) _ 6 101
19(4) _ 18 125
38(6) 4 9 150
increase, partly due to increased numbers of patients with leukaemia. Large numbers of streptococci have been isolated, particularly from patients with hepatocellular liver disease. There has been a marked increase in the number of anaerobes isolated—from 1 of 87 (1 • 1 %) in 1972 t o l 8 o f l 2 5 ( 1 4 % ) i n l 975. Although we changed our routine practice in 1972-73 by starting to use Thiol broth, we consider that the decisive factor in the increase in the number of anaerobes isolated was the setting up of an anaerobic section in our laboratory. This development increased our isolation rate of anaerobes not only from blood cultures but also from other specimens generally. We consider that this increased isolation rate is attributable more to the change in awareness and organization of our resources than to simple changes in media employed. Bacteraemia may develop as a complication of a great variety of infections in many different parts of the body. Important predisposing factors include trauma, obstructive lesions, instrumentation, immunosuppression, diabetes and malignant disease.
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 31, 2015
1972 1973 1974 1975 1976*
No. of patients with bacteraemia
% Significant positives cultures
Bacteraemia
85
During the last 40 years increasing numbers of patients with compromised defence mechanisms have been admitted to hospital for active medical and surgical treatment including invasive investigational techniques and therapy which may greatly increase the risks of infection. Special investigations
Table III. Investigations Blood cultures (more than one, including anaerobic) Full blood count (including platelets; buffycoat Gram stain) Urea, electrolytes, creatinine (Blood for serum storage—'antibodies') Urine—microscopy, culture, ward tests Swabs—septic areas; ulcers; i.v. sites; tracheostomy Specimens—drainage fluid; pus; sputum; ascites; dialysis fluid; ends of i.v. cannulae. Additional Tests Screen for fibrin degradation products Blood group and save serum for cross-match Liver function tests CXR (abdo X-rays)] s h o u , d n Q t d e ) a y t r e a t m c n t Blood gases and pH CVP readings
Antibacterial chemotherapy
Antibacterial treatment, although of great importance, is only one part of the total management of bacteraemia. Recommendations for antimicrobial therapy for bacteraemia with adult dosages are summarized in Table IV. Gentamicin is still the first choice in treating shock of unknown bacterial cause, before the results of blood cultures are known. If the source of sepsis is the biliary tract, alimentary tract, female genital tract, gangrenous tissue or an aspiration pneumonia, anaerobes are likely to be implicated and metronidazole or clindamycin should be added. Unfortunately, clindamycin occasionally causes pseudomembranous colitis, while metronidazole has not been recognized as having any major toxicity during short courses of 7 to 10 days. Moreover, it has been shown that clindamycin and lincomycin interfere with the bactericidal action of gentamicin and tobramycin against colifonns (Riff & Matulionis, 1975). This is a phenomenon which has been clinically suspected by the present authors, and is another reason for preferring metronidazole at the present time.
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 31, 2015
The investigations that are usefully undertaken in patients with suspected bacteraemia are summarized in Table III. It is crucial to obtain blood cultures and other specimens for microbial investigation before antibiotics are started.
86
P. Noooe, R. L. Abeysundere and J. M. Bradley
Table IV. Antibiotic chemotherapy
In patients who are neutropoenic (
