Rapid Responses to:
|
|
lactam monotherapy versus 
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Neutropenic or not?
- Robert Townsend (19 March 2004)
-
Re: Neutropenic or not?
- Mical Paul, Leonard Leibovici (22 March 2004)
-
severe sepsis versus patients at lower risk of death?
- Joseph C Watine (23 March 2004)
-
Are children, sometimes, little adults as well ?
- Jean-francois Hartmann (24 March 2004)
-
Beta-lactam and aminoglycoside combination therapy. The role of different aminoglycoside dosing regimens.
- Peter A Riley (25 March 2004)
-
A case for antibiotic combination therapy against pseudomonas infection remains
- RICHARD P COOKE, GED DEMPSEY, RACHEL A SEN, CHRISTOPHER WHITEHEADT (2 April 2004)
-
Beta-lactam/aminoglycoside combination therapy should still be considered for patients with severe sepsis
- Gavin D Barlow (7 April 2004)
-
Beta-lactam/ aminoglycoside combination therapy in severe P. aeruginosa infections?
- Bart J.M. Vlaminckx, I.M. Hoepelman, Profesor of Medicine, Head of Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht (22 April 2004)
-
Use of aminoglycosides with beta-lactams
- Christopher D Settle (23 April 2004)
-
Simplistic and inaccurate about anitbiotics
- Gunnar S Simonsen, Jan Erik Berdal, Dag Berild, Arnfinn Sundsfjord (28 June 2004)
-
Is combination therapy with betalactam plus aminoglycoside (AGL) improving the outcome of nosocomial meningitis in children? (letter)
- Vladimir Krcmery, M. Bošnakova, E. Grey, L. Pevalova, T. Šagat, K. Kralinsky, K. Holečkova, I. Stankovič, I. Balik, I. Šula, P. Jarčuška, B. Rudinsky (1 April 2005)
|
|
|||
|
Robert Townsend, Specialist Registrar Microbiology, Northern General Hospital, Sheffield S5 7BQ
Send response to journal:
|
Dear Sir, In "this week in the BMJ" states "in patients with neutropenia" whereas the study selection in the article states "for patients without neutropenia". At other points in the paper it also states "without neutropenia" given the importance of the conclusions I thought it was a point worth clarifying. Competing interests: None declared |
|||
|
|
|||
|
Mical Paul, Consultant Dept. of Medicine, Rabin Medical Center, 49100 Petah Tiqva, Israel, Leonard Leibovici
Send response to journal:
|
Dear Sir, The present review included studies on non-neutropenic, immunocompetent patients. There is a mistake in 'This week in the BMJ'. We have reviewed the same question in neutropenic patients in a former article (1). Reference Paul M, Soares-Weiser K, Leibovici L. Beta-lactam versus beta-lactam- aminoglycoside combination therapy for fever with neutropaenia: systematic review and meta-analysis. BMJ. 2003; 24;326:1111-5. Competing interests: None declared |
|||
|
|
|||
|
Joseph C Watine, Consultant, Laboratory Medicine Hôpital de Rodez, France
Send response to journal:
|
As already said last year [1], it is perhaps regrettable that Paul et al.'s statistical analysis did not distinguish patients with septic shock, or severe sepsis, from other patients at lower risk of adverse outcome. Reference: [1] http://bmj.bmjjournals.com/cgi/eletters/326/7399/1111#33591 Competing interests: None declared |
|||
|
|
|||
|
Jean-francois Hartmann, PICU Hospital Robert Debre, 75019 Paris, France
Send response to journal:
|
Sir, I read with deep interest this week's paper by Mical Paul et al. Although clinical research involving children is indeed scarce when compared with adult-based data, I find the usual practice among non- pediatric review groups to exclude pediatric data an unwelcomed choice leading to delayed or postponed application of adult-based evidence to pediatric patients. Beyond the neonatal and infant periods, children can probably, now and then, be considered little adults from standpoints such as the one of this paper. The limited number of children included in that systematic review will be used as a placating argument to dismiss further discussion by pediatric colleagues unwilling to face Mical Paul's conclusions. A subgroup of pediatric data would have help some of us corner some of them. Competing interests: I am a pediatric intensivist. |
|||
|
|
|||
|
Peter A Riley, Consultant Medical Microbiologist Department of Medical Microbiology, St George's Hospital, Blackshaw Road, London, SW17 0QT
Send response to journal:
|
Sir, in their review and meta-analysis, Paul et al recommend that addition of an aminoglycoside to beta-lactams should be discouraged as the fatality remains unchanged, while the risk for adverse events is increased when compared to beta-lactam monotherapy (1). The authors also point out current evidence that suggests that aminoglycoside monotherapy may be inadequate for infections outside the urinary tract. Might aminoglycosides become obsolete? I for one would need to have further evidence before ceasing to use these agents. The trials analysed by Paul et al, were performed between the years 1968 and 2001. In the late 1980s and early 1990s several studies were published that demonstrated the advantages of a single daily dose of an aminoglycoside compared to the then convention of divided doses twice or three times a day (2, 3, 4, 5, 6, 7). These trials showed either equal or superior therapeutic benefits and also in most cases reduced or similar levels of toxicity. Many hospitals now favour this approach above the conventional divided dosing regimens. In their study, Paul et al do not discuss whether there were any differences in fatality or toxicity in the trials where single dosing of aminoglycosides combined with beta-lactams were employed compared to twice or thrice daily dosing in combination with beta-lactams, but instead pool these different approaches together and then compare them to beta-lactam monotherapy. Furthermore, I am concerned that they also do not differentiate between the various aminoglycosides. Not all organisms are susceptible to all aminoglycosides. An example would be Pseudomonas aeruginosa which commonly can be resistant to gentamicin but susceptible to amikacin. Resistance may therefore be the cause of bacteriological and treatment failure. Until these further analyses of the trial data are forthcoming I would caution against ceasing to use aminoglycosides in combination with beta-lactams. References 1. Paul M, Benuri-Silbiger I, Soares-Weiser K, Leibovici L. Beta- lactam monotherapy versus beta-lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta- analysis of randomised trials. BMJ 2004; 328: 668-72. 2. Sturm AW. Netilmicin in the treatment of gram-negative bacteremia; single daily versus multiple daily dosage. J Infect Dis 1989; 159: 931-37. 3. ter Braak EW, de Vries PJ, Bouter KP, van der Vegt SG, Dorrenstein GC, Nortier JW et al. Once-daily dosing regimen for aminoglycoside plus beta-lactam combination therapy for serious bacterial infections; comparative trial with netilmicin and ceftriaxone. Am J med 1990; 89: 58- 66. 4. Nordstrom L, Ringberg H, Cronberg S, Tjernstrom O, Walder M. Dose administration of an aminoglycoside in a single daily dose affect its efficacy and toxicity. J Antimicrob Chemother 1990; 25: 159-73. 5. deVries PJ, Verkooyen RP, Leguit P, Verbrugh HA. Prospective randomized study of once-daily versus thrice-daily netilmicin regimens in patients with intraabdominal infections. Eur J Clin Microbiol Infect Dis 1990; 9: 161-68. 6. Prins JM, Buller HR, Kuijper EJ, Tange RA, Speelman P. Once versus thrice daily gentamicin in patients with severe infection. Lancet 1993; 341: 335-39. 7. Nicolau DP, Freeman CD, Bellineau PD, Nightingale CH, Ross JW, Quintiliani R. Experience with a once-daily aminoglycoside program administered to 2184 adult patients. Antimicrob Agents Chemother 1995; 39: 650-55. Competing interests: None declared |
|||
|
|
|||
|
RICHARD P COOKE, CONSULTANT MICROBIOLOGIST UNIVERSITY HOSPITAL AINTREE L9 7AL, GED DEMPSEY, RACHEL A SEN, CHRISTOPHER WHITEHEADT
Send response to journal:
|
A case for antibiotic combination therapy against pseudomonas infection remains Editor – The key message from the systematic review and meta-analysis by Paul et al is that B lactam – aminoglycoside combination therapy does not improve clinical outcome in critically-ill patients. However, only 2,530 (33%) of the patients studied after 1991 appear to have warranted intensive care and only 1,576 (20%) patients were stated to have a nosocomial infection. Also only one quoted study involving critically-ill patients appears to have been a randomised and blinded trial. Furthermore, the authors admit that few patients with Pseudomonas aeruginosa infections could be evaluated.1 These are significant weaknesses in the study. P.aeruginosa accounted for 14% of all nosocomial infections reported through the National Nosocomial Infection Surveillance reporting system and ranked second amongst Gram-negative pathogens.2 The frequency of P.aeruginosa infection, especially ventilator-associated pneumonia (VAP) is particularly high in critical care units (CCUs).3 Such infections are often difficult to cure and associated with high mortality rates.4 As the choice of effective anti-pseudomonal antibiotics is relatively limited, empirical combination therapy is often used in clinical practice due to the emerging problem of Gram-negative antimicrobial resistance and the need to “get it right first time”. As well as in-vitro synergy, better clinical outcome has been demonstrated with combination therapy.5 Though many of the studies quoted by Paul were from the 1970s and 1980s when single agent cephalosporin therapy was used,1 many CCUs would now avoid third-generation cephalosporins due to the spread of extended- spectrum beta-lactamases and the risk of Clostridium difficile colitis. Hence, an alternative approach is the use of carapenem B lactam monotherapy as front line treatment for the critically-ill. However, the development of imipenem-resistant P.aeruginosa during therapy is well recognised and has been reported between 14% and 55% of VAP patients. There is also an associated increase in cross-resistance to other anti- pseudomonal antibiotics and drug costs.4 With only limited available data, B lactam-aminoglycoside combination therapy against P.aeruginosa remains a valid therapeutic option and should continue to be included in the British National Formulary. Specific antibiotic choices should be based on local resistance patterns and therapeutic algorithms. Antibiotic resistance, fungal super-infection and aminoglycoside toxicity can all be minimised by short course therapy and a de-escalation strategy if a causative agent is identified. It would have been therefore helpful if Paul’s influential review had been linked to an editorial overview of a complicated clinical issue. Richard PD Cooke Consultant Microbiologist Ged Dempsey Consultant Anaesthetist Rachel A Sen Consultant Microbiologist Christopher Whitehead Consultant Anaesthetist University Hospital Aintree, Liverpool L7 7AL 1. Paul M, Benuri-Silbiger 1, Soares-Weiser K, Leibovici L, B lactam monotherapy versus B lactam-aminoglycoside therapy for sepsis for immunocompetant patients: a systematic review and meta-analysis of randomised trials. BMJ 2004;328: 668-672 2. National Nosocomial Infection Surveillance (NNIS) System report, data summary from October 1996 – April 1998 Issued June 1998. Am J Infect Control 1998; 26:522-533 3. Hanberger H, Garcia-Rodriguez JA, Gobernado M et al. Antibiotic susceptibility among aerobic gram-negative bacilli in intensive care units in 5 European countries. JAMA 1999;281:67-71. 4. Javier A, Pujol M. Nosocomial antibiotic resistance in GNB at the ICUs. Clin Pulm Med 2004;11:71-83. 5. Chestre J, Fagon JY. Ventilator-associated pneumonia. Am J Resp Crit Care Med 2002;165:867-903. Competing interests: None declared |
|||
|
|
|||
|
Gavin D Barlow, Acting Consultant in Infectious Diseases/Internal Medicine Dept. of Infectious Diseases, Castle Hill Hospital, Cottingham, East Yorkshire. HU16 5JQ
Send response to journal:
|
Paul et al make a laudable attempt to synthesise the data on the use of beta-lactam/aminogylocoside combination therapy for sepsis. Unfortunately their primary research question lacks the necessary focus to usefully inform UK clinical infection practice, which is increasingly burdened by bacterial resistance to beta-lactams. The important question in the UK is whether the addition of gentamicin to a beta-lactam in a patient with suspected severe Gram positive (e.g. staphylococcal endocarditis) or Gram negative (e.g. intra-abdominal infection) sepsis is better, worse or equal to monotherapy or ‘upgrading’ to other agents such as carbapenems and glycopeptides. This question cannot be answered by a systematic review in which only 20 (31%) of the 64 studies included used gentamicin, the most commonly prescribed aminoglycoside in the UK. Are all aminoglycosides equal? The studies also use a wide range of beta-lactam agents, many of which are not used in the UK, and there is considerable inter- and intra-study variation in the types of infection treated. No data is presented about the aminoglycoside dosing and monitoring regimens used in the studies and what proportion of patients were in the sub-therapeutic, therapeutic and toxic ranges. This data may not have been reported in the original studies, but it is clearly an important consideration given the potential impact on outcomes. Although the study found a higher rate of nephrotoxicity in aminoglycoside treated patients, it is interesting that discontinuation was similar in both groups. The importance of this systematic review lies not in the results or conclusions, which are clearly flawed, but in the reminder it will give clinicians to ask: Does this patient really need an aminoglycoside and is the risk-benefit ratio favorable? Until more specific data is available, however, clinicians in the UK should still consider using adequately monitored gentamicin in patients with severe sepsis and according to local bacterial epidemiology. Competing interests: None declared |
|||
|
|
|||
|
Bart J.M. Vlaminckx, Resident in Medical Microbiology University Medical Center Utrecht, 3584CX, I.M. Hoepelman, Profesor of Medicine, Head of Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht
Send response to journal:
|
Dear Sir, In their review and meta-analysis, Paul et al. conclude that the addition of an aminoglycoside to beta-lactam therapy for sepsis in immunocompetent patients should be discouraged (1). Case-fatality ratios remain unchanged with the addition of an aminoglycoside whereas nephrotoxicity was much more common. In subgroup analysis regarding patients with P. aeruginosa infections their conclusions remain identical. Nonetheless, the authors state that relatively few patients could be included and reference is made to a prospective, observational study of 200 consecutive patients with P. aeruginosa bacteraemia, conducted between 1982 and 1986 (2). In this study, Hilf et al. found that combination therapy was significantly better than monotherapy in improving outcome. The difference in mortality between patients receiving combination therapy (27%) and monotherapy (47%) was significant. With reference to this study, others (3) have also emphasized that “combining an antipseudomonal beta- lactam with an aminoglycoside or ciprofloxacin is likely to obtain a much better outcome than monotherapy”. It is important to realize that in this very influential study 186 of 200 patients received antipseudomonal therapy. 143 Patients received combination therapy, which usually consisted of piperacillin or ticarcillin combined with tobramycin or gentamycin. Of 43 remaining patients, 37 received an aminoglycoside alone and only six received an antipseudomonal beta-lactam. The inferior nature of monotherapy in this study thus might represent the inferiority of aminoglycoside monotherapy alone and is therefore not in contradiction to the finding of Paul et al. that the addition of aminoglycosides should also be questioned for severe P. aeruginosa infections. Further studies are really needed to answer the important question of the value of combination therapy in severe P. aeruginosa infections. References 1. Paul M, Benuri-Silbiger I, Soares-Weiser K, Leibovici L. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta- analysis of randomised trials. BMJ 2004; 328: 668-72. 2. Hilf M, Yu VL, Sharp J, Zuravleff JJ, Korvick JA, Muder RR. Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med.1989; 87: 540-6. See also comment in: Am J Med 1991 Jan; 90: 135. 3. Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med 2002;165: 867-903. Competing interests: None declared |
|||
|
|
|||
|
Christopher D Settle, Consultant Microbiologist Sunderland Royal Hospital, Kayll Road, Sunderland, SR4 7TP.
Send response to journal:
|
Dear Sir, I would be interested to hear the authors’ response to several issues of concern with this paper. Forty-three trials were eventually included. Of the 43 studies analysed for all-cause mortality, 31 compared beta-lactam X against beta- lactam Y plus aminoglycoside, e.g. cefoxitin vs. penicillin and gentamicin. Comparison of outcomes in these groups is therefore unreliable. There are 12 studies comparing beta-lactam X against beta-lactam X plus aminoglycoside. Endocarditis is a specific entity in itself and appendicitis does not usually meet the criteria for severe sepsis, so there are eight studies left which could help determine whether the addition of an aminoglycoside in severe sepsis makes a difference. All cause mortality is then 71/546 (monotherapy) vs. 67/543 (combination therapy). This is not going to show a significant difference, however the numbers analysed are now much smaller and most of these studies do not appear to have studied once daily aminoglycoside therapy which is currently thought to provide optimal bactericidal activity with the same or lower toxicity.(1) Comment is passed that development of resistance was no less in the combination therapy groups. A failure to reduce bacterial superinfection or colonisation rates is cited as evidence of this. In fact these two parameters have very little to do with concerns about resistance developing in the pathogen being treated, which is the primary concern. Combination therapy is not intended to prevent subsequent infection with other organisms, or colonisation with resistant organisms, but is rather to reduce the risk that the organism being treated will develop resistance itself. Only nine of 64 studies looked at resistance in pre treatment isolates and only six out of 64 carried out surveillance cultures. From this information it seems hard to draw definite conclusions about the effects of an additional aminoglycoside on the development of resistance. The issue of beta-lactam therapy, with or without an aminoglycoside, for Pseudomonas aeruginosa infection is certainly not resolved. The author admits that “only few patients with documented P. aeruginosa infections could be evaluated”. In addition they state “The quality of included studies was poor overall”. Therefore, I find the conclusion that “In the treatment of sepsis the addition of an aminoglycoside to beta-lactams should be discouraged” rather difficult to accept. Perhaps targeted research in specific groups of septic patients, treated with a particular beta-lactam (with or without a specific aminoglycoside) would help to clarify the position. From the evidence supplied, I feel the case that “ beta-lactam - aminoglycoside combination therapy does not improve clinical outcomes in patients with severe infections” remains unproved. References. 1. Freeman CD, Nicolau DP, Belliveau PP, Nightingale CH. Once-daily dosing of aminoglycosides: review and recommendations for clinical practice. J Antimicrob Chemother. 1997 Jun;39(6):677-86. Competing interests: None declared |
|||
|
|
|||
|
Gunnar S Simonsen, Senior consultant Department of Microbiology, University Hospital of North Norway, NO-9038 Tromsř, Norway, Jan Erik Berdal, Dag Berild, Arnfinn Sundsfjord
Send response to journal:
|
In their BMJ paper of March 2004, M. Paul et al. conclude that “In the treatment of sepsis, the addition of an aminoglycoside to beta-lactams should be discouraged”. We find this conclusion inaccurate and simplistic as it is based on an analysis where all beta-lactams are grouped together irrespective of their clinical and ecological properties. From the list of studies included in their meta-analysis it is evident that the majority of patients were recruited from trials where the beta-lactam monotherapy arm was represented by a very broad-spectrum antibiotic such as a third- generation cephalosporin or a carbapenem. In many instances the beta- lactam in the combination regimen was also a very broad-spectrum agent. The work by Paul et al. consequently demonstrates that there is little to gain from using an aminoglycoside in addition to a broad-spectrum beta- lactam in the treatment of sepsis. However, the paper does not determine the value of aminoglycosides as a means of limiting this indiscriminate use of broad-spectrum beta-lactams. The Nordic countries have a long tradition of treating sepsis in immunocompetent patients with a combination regimen of an aminoglycoside and a more limited-spectrum beta- lactam such as ampicillin or penicillin G. By this approach, the total usage of advanced beta-lactams has been limited. It is widely recognized that there is an association between total usage of broad-spectrum beta- lactams and the occurrence of antibiotic resistance phenotypes such as extended spectrum beta-lactamase production in Enterobacteriaceae, carbapenem resistance in Pseudomonas aeruginosa and glycopeptide resistance in enteroccocci. These ecological associations cannot be evaluated in individual trials but are evident from secular trends in antibiotic usage and antimicrobial resistance among regions and countries. Unfortunately, it is uncertain whether the favourable situation we presently enjoy in the Nordic countries in terms of low prevalences of antibiotic resistance can be re-established in countries where over- and misuse of broad-spectrum agents has rendered our more conservative regimens useless. It is nevertheless important to require a high level of precision when general recommendations are made as in the aforementioned paper. In our view, a combination regimen of an aminoglycoside and a narrow-spectrum beta-lactam is clinically appropriate and ecologically preferrable in the treatment of sepsis when local resistance data indicate that this approach will be effective. The issue of toxicity of aminoglycosides is complex as it depends on several parameters related to both the patient and the treatment regimen. Even if it was not mentioned, the dosing of aminoglycosides in the included studies were probably three times daily. It is now well-known that the efficacy of aminoglycosides depends on Cmax, and it has also been shown that once-daily dosage of these agents not only has a higher efficacy but also less side-effects in comparison to three-times daily dosage. The conclusions in the meta- analysis with regard to aminglycoside toxicity are therefore of little relevance to modern treatment regimens. Competing interests: None declared |
|||
|
|
|||
|
Vladimir Krcmery, professor OUSA Heydukova 10, 812 50 Bratislava , Slovak republic, M. Bošnakova, E. Grey, L. Pevalova, T. Šagat, K. Kralinsky, K. Holečkova, I. Stankovič, I. Balik, I. Šula, P. Jarčuška, B. Rudinsky
Send response to journal:
|
Sir, recently a paper was published in Br Med J from Paul et al. (1), presenting a metanalysis of the role of the combination of aminoglycosides with betalactams in the therapy of sepsis. The conclusion of metanalysis of 52 studies was that addition of an aminoglycoside did not improve the outcome in bacteremia/sepsis, but increased the toxicity of the treatment. We assessed all children with nosocomial meningitis (NM) treated with combination therapy (20) in a national antimicrobial survey within 12 years and compared them to the 137 cases of NM, concerning risk factors and outcome. AMP + gentamicin or cefotaxim/ceftazidime with netilmicin have been considered to be state of the art therapies in both nosocomial meningitis and endocarditis.(2) An EORTC study supported the use of amikacin for the first days of sepsis due to multiresistant organisms such as ESBL-producing enterobacteriaceae, VAN-resistant enterococci.(3) Methicillin-resistant streptococci often require combination of at least two available effective antibiotics. However metanalysis included in to the model all abovementioned cases apart from endocarditis and meningitis. In our retrospective analysis we considered as combination therapy an addition of aminoglycoside to either betalactam or glycopeptide or clindamycin for at least 5 days. In this letter therefore we would like to show what was the prognosis of cases treated with combination therapy. Table 1 shows risk factors and outcome in those treated with combination therapy (defined above) or monotherapy (meropenem, 3.-4. generation cephalosporine, vancomycin, chloramphenicol, ciprofloxacin, cotrimoxazole). There was no major difference in risk factors. More patients with Ps. aeruginosa (20% vs 7%; P<0.045) received combination therapy. Also more Acinetobacter baumanii NM received combination of betalactam (cephalosporin or meropenem) plus aminoglycoside than monotherapy (35% vs 7.5%; P<0.01). Concerning outcome, there was no difference in attributable mortality (25% vs 14%; NS) neither in the number of sequels (14% vs 10%). Therefore, we have not been able to document a benefit of combination of aminoglycosides to betalactam or carbapenem in nosocomial meningitis. This was similar to the cases of sepsis, where survival of patients did not improve with combination therapy. Combination therapy did not increase the chance of appropriateness of the therapy. 30% of those on combination therapy were considered as inappropriately treated in comparison to 2.8% of those on monotherapy (P<0.01). References: 1. Paul M, Benuri-Silbiger I, Soares-Weiser K, Leibovici L: Adding aminoglycoside to betalactam does not improve results. BMJ. 2004; 328: 668 2. Leibovici L, Shraga I, Drucker M, Konigsberger H, Samra Z, Pitlik S D: The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Inf Med 1998; 244: 397-386 3. EORTC. Ceftazidime combined with a short or long course of amikacin for empirical therapy of gram-negative bacteremia in cancer patients with granulocytopenia. The EORTC International Antimicrobial Therapy Cooperative Group. N Engl J Med 1987; 317: 1692-8 Address: Prof. Vladimir Krcmery, MD, FACP, FRCP
Table 1: Outcome in combination therapy versus monotherapy Combination therapy (A) Monotherapy (B) p A vs B 1. Underlying disease VLBN/prematurity 1 (5) 35 (24.5) 0.04 Neoplasia 3 (15) 22 (16) NS Diabetes, cystic fibrosis 4 (20) 14 (10) NS Perinatal pathology (hydrocephalus) 3 (15) 15 (11) NS 2. Type of surgery Trauma 5 (25) 17 (13) NS Tumor resection 4 (20) 13 (9) NS VP-S insertion, change, drainage 3 (15) 61 (47) 0.04 Spinal puncture, evacuation absces hemat. 2 (10) 6 (4.7) NS Decompressive craniotomy, ventriculostomy 6 (30) 13 (9) NS Hemorrhage punction/derivation 6 (30) 11 (8) NS Congenital malformation operation 1 (5) 20 (14) NS 3. Microbiology Positive blood cultures 2 (10) 39 (26) NS Multiple positive CSF cultures 2 (10) 23 (17) NS Candida 0 12 (8) NS Coagulasa negative staphylococci – SE 5 (15) SE rid 68 (49) NS S.hominis, S.warneri, S.xylosus, S.hemolyticus, S.cohni 1 (5) Non SE CONS 9 (7) NS Enterobacteriaceae 1 (5) 22 (16) NS Streptococci (SP, S.virid, S.agalactiae) 2 (10) 8 (6) NS Enterococci 0 9 (7) NS S.aureus 0 12 (8) NS Acinetobacter 7 (35) 10 (7.5) 0.01 Pseudomonas 4 (20) 9 (7) 0.045 4. Outcome/ sequels Died of infection 5 (25) 19 (14) NS Cured no sequels 14 (70) 100 (72) NS Neurological sequels 1 (5) 20 (14) NS Inappropriate therapy (in vitro resist.) 6 (30) 4 (2.8) 0.01 VLBN – neonates with very low birth weight Competing interests: None declared |
|||