Dynamic calcium-mediated stress response and recovery signatures in the fungal pathogen, Candida albicans.

IMPORTANCE: Intracellular calcium signaling plays an important role in the resistance and adaptation to stresses encountered by fungal pathogens within the host. This study reports the optimization of the GCaMP fluorescent calcium reporter for live-cell imaging of dynamic calcium responses in single cells of the pathogen, Candida albicans, for the first time. Exposure to membrane, osmotic or oxidative stress generated both specific changes in single cell intracellular calcium spiking and longer calcium transients across the population. Repeated treatments showed that calcium dynamics become unaffected by some stresses but not others, consistent with known cell adaptation mechanisms. By expressing GCaMP in mutant strains and tracking the viability of individual cells over time, the relative contributions of key signaling pathways to calcium flux, stress adaptation, and cell death were demonstrated. This reporter, therefore, permits the study of calcium dynamics, homeostasis, and signaling in C. albicans at a previously unattainable level of detail.

Allopeptide-specific CD4(+) T cells facilitate the differentiation of directly alloreactive graft-infiltrating CD8(+) T Cells.

To investigate the mechanism of CD4(+) T-cell help during the activation and differentiation of directly alloreactive CD8(+) T cells, we examined the development of obliterative airways disease (OAD) following transplantation of airways into fully mismatched recipient mice deficient in CD4(+) T cells. BALB/c trachea allografts became fibrosed significantly less frequently in B6 CD4(-/-) recipients as compared to wildtype controls. Furthermore, class I-directed cytotoxicity failed to develop in the absence of CD4(+) T cells. The infiltration of graft tissue by primed L(d)-specific directly alloreactive 2C CD8(+) T cells was not found to depend on the presence of CD4(+) T cells. Nevertheless, graft-infiltrating 2C CD8(+) T cells failed to express CD69 and granzyme B when CD4(+) T-cell help was unavailable. Importantly, reconstitution of B6 CD4(-/-) recipient mice with graft peptide-specific TCR-Tg CD4(+) T cells (OT-II or TEa) capable of recognizing antigen only on recipient APC allowed for full expression of CD69 and granzyme B by the directly alloreactive CD8(+) T cells and restored the capacity of recipients to reject their allografts. These results demonstrate that indirectly alloreactive CD4(+) T cells ensure the optimal activation and differentiation of graft-infiltrating directly alloreactive CD8(+) T cells independent of donor APC recognition.

Computed tomographic colonography (CTC) performance: one-year clinical follow-up.

AIM: Computed tomographic colonography (CTC) represents a valuable advance in imaging technology for patients with colonic symptoms who are unfit for or fail to complete investigation with conventional techniques of colonoscopy or barium enema. The aim of this study was to examine whether CTC was sufficient to exclude colorectal cancer in such a population. As our patients were unfit for or unable to complete conventional investigations, we used 1 year clinical follow-up to exclude colonic malignancy. MATERIALS AND METHODS: CTC examination was performed using multi-slice CT in patients fitting pre-determined criteria. All patients who had completed 12 months of follow-up after CTC were included. Data were extracted from patient records and lack of presentation within the 12 months following a negative CTC was assumed to equate to lack of colorectal cancer at initial investigation. RESULTS: One hundred and twelve patients underwent CTC with a median age of 78 years (range 39-95) and median follow-up of 18 months (range 12-26). CTC detected 7 colorectal cancers, with 3 false positives and 1 false negative, giving a sensitivity of 87.5% and specificity of 97.1% for the detection of colorectal cancer. CONCLUSIONS: CTC is a good imaging tool for the exclusion of colorectal cancer in a population unfit for or unable to complete colonoscopy or barium enema, with reasonable sensitivity and specificity for detection of colorectal cancer. However, the optimum investigative strategy for fitter symptomatic individuals is still debated and should be clarified by the results of ongoing randomised controlled trials.

Patient quality of life after successful restorative proctocolectomy is normal.

OBJECTIVE: To measure quality of life (QoL), using validated health status instruments, of patients with functioning IPAA for CUC. PATIENTS AND METHODS: Between 1986 and 1997, a total of 77 patients had an IPAA. Thirteen patients were excluded [6 excised, 3 awaiting ileostomy closure, 2 lost to follow up, 2 serious unrelated illnesses]. Postal survey using SF36 and EuroQol questionnaires. Age, sex, year of pouch construction and stool frequency were documented. RESULTS: Fifty-six patients (87.5%) replied. Male:female ratio; 3:2. Median age; 34 years (range 13-64). Median time since pouch construction; 4 years (range 1-10 years). Median SF36 scores (range); physical function 86.6 (0-100), physical role 81.6 (0-100), body pain 78.4 (22-100), general health 61.6 (5-100), vitality 57.6 (5-100), social function 75.4 (25-100), emotional role 83.5 (0-100), mental health 70.7 (16-100). All the SF36 scores were within the normal range, as were the EuroQol scores. Median EuroQol score (range); 0.85 (-0.07-1.0). Median EuroQol thermometer score (range); 83.3 (20-100). There was no correlation between objective QoL score and age, gender, stool frequency and year of pouch construction. CONCLUSION: The QoL for patients with a functioning IPAA for CUC measured using validated health status instruments is normal. Age, gender, stool frequency and year of construction do not affect QoL outcome after the IPAA for ulcerative colitis.

Enhancing medical student consultation request skills in an academic emergency department.

The purpose of this study was to develop an educational protocol to enhance the communication skills of medical students when requesting specialty consultation. A protocol consisting of a worksheet and oral instructions was created to teach nine criteria of effective consultation requests, derived from the existing literature. Consultation requests made by senior medical students using the protocol were evaluated and compared to consultation requests made by Emergency Medicine residents who did not complete the educational protocol. Forty-two medical student consultation requests and 50 Emergency Medicine resident consultation requests were evaluated. The students included five of the nine criteria in their consultation requests significantly more often than the residents. The median number of criteria included by the students was eight, while the median number of criteria included by the residents was six. This study shows that senior medical students can be taught to communicate effectively with specialists when requesting consultations.

In vitro antimicrobial effects of various combinations of penicillin and clindamycin against four strains of Streptococcus pyogenes.

Previous studies using mouse models of Streptococcus pyogenes necrotizing fasciitis demonstrated that clindamycin had greater efficacy than penicillin. Frequently both agents are used concurrently in the treatment of severe S. pyogenes infections. This study investigated interactions between penicillin and clindamycin. E-test and broth microdilution assays suggested additivity or indifference, while timed-killing assays demonstrated concentration-dependent variable effects. Timed-kill studies utilizing clinical concentrations suggest that there is no antagonism with the combination of drugs but that the combination does not have a bactericidal advantage over either penicillin or clindamycin alone.

Opiate and sedative dependence predicts a poor outcome for patients receiving home parenteral nutrition.

BACKGROUND: Home parenteral nutrition (HPN) is used to treat intestinal failure. A minority of HPN patients are dependent on opiates and benzodiazepines to control pain and anxiety. The aim of this study was to determine what effects such drug dependence had on patient outcomes. METHODS: Ten dependent patients were prospectively compared with 10 well-matched, nondependent HPN patients for the same 12-month period. Episodes of line sepsis and other complications were documented and the cost of treatment estimated. Health status was measured using the SF36 and EuroQol instruments. RESULTS: The dependent group had significantly more episodes of central line sepsis (p = .0007) as well as other complications (p = .0002). This led to significantly longer periods of inpatient care (p = .0004) and therefore higher costs of treatment. Health status was lower in the dependent group; they reported more pain (p = .04) and less energy (p = .04). CONCLUSIONS: The complication rate and increased cost of treatment for opiate- and sedative-dependent patients receiving HPN significantly detract from the overall outcome of this therapy.

Assessing the quality of life of patients with intestinal failure on home parenteral nutrition.

BACKGROUND: A study was performed to measure the quality of life of patients receiving home parenteral nutrition (HPN). Quality of life is an important determinant of the effectiveness of health technologies, but it has rarely been assessed in patients receiving HPN. AIMS: To measure quality of life and highlight any moderating factors. PATIENTS AND METHODS: Quality of life was measured using two validated instruments (SF 36 and EuroQol) in 51 patients with intestinal failure. All patients had benign disease, the commonest being Crohn's disease (n = 35). RESULTS: HPN patient scores were worse for six of eight SF 36 domains (p < 0.05) compared with standard population scores. Younger patients (< 45) had good scores but older patients (> 55 years) scored significantly less. Patients addicted to narcotic substances had very low scores. EuroQol utility scores confirmed the SF results. Forty one patients reported that they felt too ill to work and only five were in full time work or education. CONCLUSIONS: The health status profile of our young patients on HPN was good compared with the normal population. The poorest scores were in older patients and those dependent on narcotic drugs. This has clinical and economic relevance when considering such patients for HPN.

Home parenteral nutrition: a systematic review.

OBJECTIVES: The objective of this Review was to locate, appraise and summarise evidence from scientific studies on home parenteral nutrition (HPN) in order to answer specific research questions on the effectiveness of this technology. The following questions were asked. What patients have received HPN? What has been the experience of patients on HPN programmes? How have HPN programmes been organised, and what techniques and equipment have been used, and to what effect? What comparative information is available on effectiveness? What evidence exists for the cost-effectiveness of HPN? What questions about the provision of HPN could be answered with additional research, and what studies would be most suitable? DATA SOURCES: A comprehensive list of studies was provided by an extensive search of electronic databases (including MEDLINE, Embase, Science Citation Index, Uncover, Cinahl, Caredata, Food Science and Technology Abstracts, NTIS, Pascal, Psychlit, and Economic Literature Index), relevant journals (including Journal of Parenteral and Enteral Nutrition, Clinical Nutrition, American Journal of Clinical Nutrition, Nutrition, Clinical Gastroenterology, Nutrition Reviews, Annals of Nutrition and Metabolism, Nutrition and Cancer, Nutrition and Health, and Journal of Paediatric Nutrition and Metabolism), and scanning of reference lists, as well as other search strategies outlined in the protocol. STUDY SELECTION: Studies relevant to the questions were selected. The inclusion criteria were fairly broad because of the quality of the studies located. DATA EXTRACTION: Data extraction forms were used to collect data from studies included in the review. The data was checked by a second researcher to reduce error. DATA SYNTHESIS: Quantitative analysis was difficult owing to the type of studies located. The data is discussed in a qualitative manner. Where complication rates have been given, we have attempted to combine the results in a quantitative manner. RESULTS: The age and sex of patients on HPN varies according to the underlying disease but, on the whole, patients are young (see Tables 4a and 4b). There are trends showing an increased use of the technology at the extremes of the age range. There are marked differences between countries on the underlying diseases for which HPN is indicated. For example, many more patients with an underlying malignancy are treated in Italy and the USA than in the UK (40-67% versus 8%). Morbidity rates for the majority of patients are acceptable (see Table 8), the complications tend to be related to the central venous catheter. It is fairly clear that a minority of patients are susceptible to recurrent problems and that many patients have very few complications. The mortality rate for HPN patients (see Table 10) was good for those patients with benign underlying disease (for example, 5% of Crohn's HPN patients die per year), and there are very few reports of patients dying from complications of the technology. The survival of those with malignant disease and AIDS is poor, almost all having died from the underlying disease at one year; despite this, most programme growth worldwide is due to an increase in the numbers of patients with these diagnoses (see Table 5). Quality of life is reasonable for patients with benign disease (see Table 9); no studies were found that examined the quality of life of HPN patients with malignant disease. Economic analysis shows that the cost of HPN treatment is cheaper than the alternative of in-patient care (see Table 18). There is a paucity of comparative studies examining different aspects of the technology, and this accounted for the majority of gaps in the evidence. CONCLUSIONS: The use of HPN for benign intestinal failure is supported by evidence from the scientific studies located. There are, however, large gaps in the evidence, particularly relating to the use of HPN in malignant disease and AIDS. A programme of research is suggested at the end of this review.

Cost-utility analysis of home parenteral nutrition.

An economic evaluation of home parenteral nutrition (HPN) for intestinal failure is presented. The cost-utility of HPN and factors affecting the cost-utility ratio were examined to determine whether current practice is the most efficient way of treating intestinal failure. Quality-adjusted life-years (QALYs) gained were measured using a validated health status questionnaire. The cost of treating a patient with intestinal failure was calculated, and marginal cost per QALY gained ratios were obtained. The cost per QALY for an average patient was approximately 68,975 pounds, but the value for patients over 55 years of age of about 126,865 pounds compared with approximately 58,233 pounds for those under 44 years. Treating a patient in hospital rather than at home increased the estimated cost per QALY to approximately 190,000 pounds. The current practice of home care is about 65 per cent more cost-effective than hospital care.

The evolving role of laser-assisted angioplasty in a United Kingdom district general hospital.

Fifty-five patients with occlusion of the superficial femoral artery were studied. Of these, fifty-two had claudication and three had critical ischaemia. The mean length of the occlusion was 6.8 cm. In the first phase of the study, laser-assisted angioplasty (LAA) was used. In the second phase, a Terumo guide wire (TGW) was used first and if unsuccessful, a laser probe was used. An attempt was always made to push the laser probe through the occlusion without firing ('cold probe'). Otherwise, the Nd-YAG laser was activated ('hot probe'). The overall success rate for LAA alone was 79%. The TGW followed by LAA, if necessary, succeeded in 77%. The 'hot probe' resulted in four perforations; only one perforation was seen with the TGW. TGW is more straightforward to use and less likely to result in perforation making it a good first option with LAA as a backup.

Cetirizine. A review of its pharmacological properties and clinical potential in allergic rhinitis, pollen-induced asthma, and chronic urticaria.

Cetirizine, a piperazine derivative and carboxylated metabolite of hydroxyzine, is a potent histamine H1-receptor antagonist with antiallergic properties. It has marked affinity for peripheral histamine H1-receptors and, at the standard dose of 10mg daily, lacks the CNS depressant effects of standard antihistamines. In addition, it inhibits histamine release and eosinophil chemotaxis during the secondary phase of the allergic response. Results from controlled clinical trials indicate that cetirizine is an effective and well tolerated treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. Cetirizine appears to be as effective as conventional dosages of terfenadine, chlorpheniramine and hydroxyzine in relieving symptoms associated with these disorders and produces a markedly lower incidence of sedation than chlorpheniramine, hydroxyzine and several other standard antihistamines. Thus, cetirizine appears to provide a useful alternative to other 'nonsedating' antihistamines; cetirizine may also have a future role in the treatment of allergic asthma and certain forms of physical urticaria.

Teicoplanin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential.

Teicoplanin is a glycopeptide antibiotic with a molecular structure which is related to that of vancomycin. Gram-positive bacteria such as staphylococci (including methicillin-resistant strains), streptococci, enterococci and many anaerobic Gram-positive bacteria are susceptible to teicoplanin in vitro. Teicoplanin has an exceptionally long half-life, allowing once-daily intramuscular or intravenous administration. Teicoplanin is clinically and bacteriologically effective against a wide variety of Gram-positive infections such as septicaemia, endocarditis, skin and soft tissue infections and infections associated with venous catheters. The drug is equally efficacious against methicillin-resistant and -susceptible staphylococci. Adverse effects with teicoplanin are generally limited to local effects or hypersensitivity reactions. While teicoplanin has the potential for ototoxicity and nephrotoxicity, the incidence appears to be quite low when recommended serum concentrations are maintained. Teicoplanin is a valuable alternative to vancomycin, and providing controlled comparative studies prove equivalent safety and efficacy between the 2 glycopeptides the more easily administered teicoplanin should become the preferred antibacterial agent.

Netilmicin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Netilmicin is a semisynthetic aminoglycoside derived from sisomicin. It is active against most Gram-negative and some Gram-positive bacteria, including many gentamicin-resistant strains. Netilmicin has proved to be effective in Gram-negative infections of the urinary tract, skin and skin structure, and lower respiratory tract, as well as in intra-abdominal infections, septicaemia and other miscellaneous infections. In some trials, the more easily implemented once daily administration of netilmicin has been as effective as multiple dosing regimens. However, further investigation is required to confirm that efficacy and safety are not compromised with once daily administration. Comparative studies have generally revealed similar clinical and bacteriological efficacies between netilmicin and gentamicin, amikacin or tobramycin. As with other aminoglycosides, the principal adverse effects of netilmicin are nephrotoxicity and ototoxicity. Although animal studies strongly suggest that these are less common with netilmicin than with related drugs, there appears to be no difference in their incidence in clinical use; in clinical trials the incidence of nephrotoxicity and ototoxicity has been low, with the symptoms in many cases being minor and reversible. Netilmicin is, therefore, an effective antibacterial drug for the parenteral treatment of severe infections, offering theoretical advantages in safety which may indicate its use for patients believed to be at risk of adverse effects.

Cefixime. A review of its antibacterial activity. Pharmacokinetic properties and therapeutic potential.

Cefixime, previously designated FK027, FR17027 and CL284635, is an orally active cephalosporin with a broad spectrum of antibacterial activity in vitro. It is particularly active against many Enterobacteriaceae, Haemophilus influenzae. Streptococcus pyogenes, Streptococcus pneumoniae and Branhamella catarrhalis, and is resistant to hydrolysis by many beta-lactamases. Cefixime has little activity against Staphylococcus aureus and is inactive against Pseudomonas aeruginosa. Cefixime is distinguished by its 3-hour elimination half-life which permits twice daily, or in many instances once daily, administration. Comparative trials, though few, indicate that the clinical and bacteriological efficacy of cefixime 200 to 400mg daily administered as a single dose or in 2 divided doses, is comparable with that of multiple daily doses of co-trimoxazole (trimethoprim + sulphamethoxazole) or amoxycillin in acute uncomplicated urinary tract infection, with that of amoxycillin, amoxycillin/clavulanic acid and cefaclor in acute lower respiratory tract infections, and with that of amoxycillin and cefroxidine in adult patients with acute tonsillitis or pharyngitis. Several comparative trials in children with acute otitis media demonstrate the similar effectiveness of cefixime 8 mg/kg daily (in 2 divided doses, or as a single daily dose), cefaclor 20 to 40 mg/kg daily and amoxycillin 40 mg/kg daily in 3 divided doses. The most frequently reported adverse effects, diarrhoea and stool changes, are usually mild to moderate in severity, transient, and mostly occur in the first few days of treatment with cefixime. Thus, cefixime is an effective orally active cephalosporin with a relatively long elimination half-life permitting a simplified treatment regimen. It is a suitable alternative to cefaclor or amoxycillin in acute otitis media and acute upper and lower respiratory tract infections, and to amoxycillin or co-trimoxazole in acute uncomplicated urinary tract infections.

Zidovudine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy.

Zidovudine (azidothymidine) is a thymidine analogue antiretroviral drug active against human immunodeficiency virus (HIV). In acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) patients, orally and intravenously administered zidovudine is effective in reducing the incidence of opportunistic infections and neoplasms, increasing helper T lymphocyte numbers, and improving survival rates and quality of life. Adverse effects include serious haematological abnormalities and severe headache, abdominal discomfort, nausea, myalgia and insomnia. In addition, neutropenia and other anaemias frequently limit zidovudine therapy and may result in a need for multiple blood transfusions, dose reductions or withdrawal of the drug. However, despite these problems and the lack of information about some aspects of zidovudine use, zidovudine provides a major hope for HIV-infected patients, and it has rapidly become the standard therapy for improving the quality and duration of the lives of AIDS and ARC patients.

Sultamicillin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Sultamicillin is the tosylate salt of the double ester of sulbactam plus ampicillin. Sulbactam is a semisynthetic beta-lactamase inhibitor which, in combination with ampicillin, extends the antibacterial activity of the latter to include some beta-lactamase-producing strains of bacteria that would otherwise be resistant. The combination of sulbactam plus ampicillin for parenteral use has previously been shown to be clinically and bacteriologically effective in a variety of infections. The chemical linkage of sulbactam and ampicillin has now produced an orally effective compound, sultamicillin, with antibacterial activity and clinical efficacy which are similar to those of the parenteral formulation. Sultamicillin has been shown to be clinically effective in non-comparative trials in patients with infections of the respiratory tract, ears, nose and throat, urinary tract, skin and soft tissues, as well as in obstetric and gynaecological infections, and in the treatment of gonorrhoea. In a small number of controlled trials, sultamicillin has shown comparable clinical efficacy to phenoxymethyl penicillin (penicillin V) and to amoxycillin (alone and in combination with clavulanic acid) in the treatment of paediatric streptococcal pharyngitis and acute otitis media, respectively; to cefaclor in the treatment of acute otitis media in adults; and to bacampicillin, cloxacillin and flucloxacillin plus ampicillin in skin and soft tissue infections in adults, children and adult diabetic patients, respectively. Sultamicillin was superior in efficacy to bacampicillin in the treatment of chronic respiratory infections, to cefaclor in the treatment of acute otitis media in adults, and to cefadroxil in the treatment of patients with complicated urinary tract infections. However, in single-dose treatment of uncomplicated gonorrhoea, sultamicillin (1500mg plus probenecid 1g) was inferior to a 2g intramuscular dose of spectinomycin. While in several studies the incidence of diarrhoea associated with sultamicillin was greater than that with comparative antibacterials, sultamicillin-associated diarrhoea was generally mild and transitory, although occasionally severe enough to necessitate discontinuation of treatment. Further studies in larger groups of patients are needed to clarify the therapeutic efficacy and safety of sultamicillin in comparison with other antibacterial regimens, and to determine the optimum single dosage for the treatment of gonorrhoea. Nonetheless, sultamicillin appears to provide a similar pharmacodynamic and pharmacokinetic profile to that of parenteral sulbactam plus ampicillin and, as such, will extend the therapeutic efficacy of ampicillin, with the further advantage of allowing treatment of patients with an oral formulation, thus avoiding the potentially adverse clinical and financial effects of prolonged parenteral therapy.

Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy.

Acyclovir (aciclovir) is a nucleoside antiviral drug with antiviral activity in vitro against members of the herpes group of DNA viruses. As an established treatment of herpes simplex infection, intravenous, oral and to a lesser extent topical formulations of acyclovir provide significant therapeutic benefit in genital herpes simplex and recurrent orofacial herpes simplex. The effect of acyclovir therapy is maximised by early initiation of treatment, especially in non-primary infection which tends to have a less protracted course than the primary episode. Long term prophylactic oral acyclovir, in patients with frequent episodes of genital herpes simplex, totally suppresses recurrences in the majority of subjects; as with other infections responding to acyclovir, viral latency is not eradicated and pretreatment frequencies of recurrence return after discontinuation of treatment. Caution should accompany the prophylactic use of acyclovir in the general population, due to the theoretical risk of the emergence of viral strains resistant to acyclovir and other agents whose mechanism of action is dependent on viral thymidine kinase. Intravenous acyclovir is the treatment of choice in biopsy-proven herpes simplex encephalitis in adults, and has also been successful in the treatment of disseminated herpes simplex in pregnancy and herpes neonatorium. Intravenous and oral acyclovir protect against dissemination and progression of varicella zoster virus infection, but do not protect against post-herpetic neuralgia. In immunocompromised patients, intravenous, oral and topical acyclovir shorten the clinical course of herpes simplex infections while prophylaxis with oral or intravenous dosage forms suppresses reactivation of infection during the period of drug administration. Ophthalmic application of 3% acyclovir ointment rapidly heals herpetic dendritic corneal ulcers and superficial herpetic keratitis. Thus, despite an inability to eradicate latent virus, acyclovir administered in therapeutic or prophylactic fashion is now the standard antiviral therapy in several manifestations of herpes simplex virus infection, and indeed represents a major advance in this regard. With the exception of varicella zoster virus infections, early optimism concerning the use of the drug in diseases due to other herpes viruses has generally not been supported in clinical investigations.

Antimicrobial therapy in neonates, infants and children.

Many antimicrobial medications may be administered to paediatric patients with a degree of impunity because they are relatively non-toxic and have a wide therapeutic margin. However, because of different pharmacokinetics from those in adults, the potential for toxicity exists with the use of some of these agents. Drug absorption in paediatric patients, either orally or parenterally, is generally similar to that in adults, except among neonates and, particularly, premature neonates. Similarly, in neonates, drug distribution is altered, plasma protein binding is decreased and hepatic metabolism and renal excretory capacity are limited by physiological immaturity. Thus, in neonates, only drugs that have pharmacokinetically derived dosage schedules should be used, and therapeutic monitoring of plasma drug concentrations is recommended during therapy with aminoglycosides, vancomycin and chloramphenicol. In older infants and children, the pharmacokinetics of antimicrobial drugs generally approximate those in adults, and recommended dosages have been determined relative to bodyweight. Therapeutic monitoring of plasma drug concentrations may be important in certain patients, such as those with major organ failure, and may be useful in cases of suspected noncompliance. Additional pharmacokinetic considerations concerning antimicrobial medication and paediatric patients are the extent to which drug therapy penetrates the cerebrospinal fluid in meningitis, and the potential for and implications of exposure of infants to antimicrobial medications excreted in breast milk.