Infections with Salmonella are an important public health problem worldwide. On a global scale, it has been appraised that Salmonella is responsible for an estimated 3 billion human infections each year. The World Health Organization (WHO) has estimated that annually typhoid fever accounts for 21.7 million illnesses (217,000 deaths) and paratyphoid fever accounts for 5.4 million of these cases. Infants, children, and adolescents in south-central and South-eastern Asia experience the greatest burden of illness. In cases of enteric fever, including infections with S. Typhi and S. Paratyphi A and B, it is often necessary to commence treatment before the results of laboratory sensitivity tests are available. Hence, it is important to be aware of options and possible problems before beginning treatment. Ciprofloxacin has become the first-line drug of choice since the widespread emergence and spread of strains resistant to chloramphenicol, ampicillin, and trimethoprim. There is increase in the occurrence of strains resistant to ciprofloxacin. Reports of typhoidal salmonellae with increasing minimum inhibitory concentration (MIC) and resistance to newer quinolones raise the fear of potential treatment failures and necessitate the need for new, alternative antimicrobials. Extended-spectrum cephalosporins and azithromycin are the options available for the treatment of enteric fever. The emergence of broad spectrum β-lactamases in typhoidal salmonellae constitutes a new challenge. Already there are rare reports of azithromycin resistance in typhoidal salmonellae leading to treatment failure. This review is based on published research from our centre and literature from elsewhere in the world. This brief review tries to summarize the history and recent trends in antimicrobial resistance in typhoidal salmonellae.

Typhoid fever is caused by Salmonella enterica serovar Typhi, a major public health concern in developing countries. Recently, there has been an upsurge in the occurrence of bacterial isolates that are resistant to ciprofloxacin, and the emergence of broad spectrum β-lactamases in typhoidal salmonellae constitutes a new challenge for the clinician. A total of 337 blood culture isolates of S. Typhi, isolated from Pondicherry, India, between January 2005 and December 2009, were investigated using phenotypic, molecular and serological methods. Of the 337 isolates, 74 (22%) were found to be multidrug resistant (MDR) and 264 (78%) nalidixic acid resistant (NAR). Isolates with reduced susceptibility to ciprofloxacin possessed single mutations in the gyrA gene. A high rate of resistance (8%) was found to ciprofloxacin. All isolates with a ciprofloxacin MIC ≥ 4 mg/L possessed both double mutations in the QRDR of the gyrA gene and a single mutation in the parC gene. Active efflux pump mechanisms were also found to be involved in ciprofloxacin resistance. Finally, a large number of PFGE patterns (non-clonal genotypes) were observed among the S. Typhi isolates. In conclusion, a high rate of ciprofloxacin resistance was observed in comparison to other endemic areas in blood culture isolates of S. Typhi from Pondicherry, India, with steadily increasing NAR but decreasing MDR isolations over the study period. This is most likely to be due to an increased use of ciprofloxacin as a first-line drug of choice over more traditional antimicrobial agents for the treatment of typhoid fever.

SummaryWe have studied, over a wide range of dilutions using techniques of clot weight, thrombelastography and scanning electron microscopy, the physical properties of a blood clot formed in vitro when fresh blood was diluted with gelatinbased colloid solutions compared with crystalloid controls. The colloid solutions tested (3.5% polygeline (Haemaccel) and 4% succinylated gelatin (Gelofusine)) produced clots that had reduced median weight (P:0.001 and P:0.018, respectively) and reduced mean shear modulus (P:0.001) compared with crystalloid controls. Scanning electron microscopy showed that the fibrin formed a less extensive mesh in the presence of the gelatin-based colloids compared with crystalloid. Reduction in clot quality with gelatin-based colloids has not been noted previously and further work is needed to ascertain if this occurs in vivo as these solutions are used frequently in patients who require full haemostatic competence. (Br. J. Anaesth. 1998; 80: 204-207) Keywords: blood, coagulation; blood, colloids; fluids, i.v.; blood, haemostasis; blood, replacement; measurement techniques, thrombelastography Plasma substitutes containing degraded and modified gelatin are being used increasingly in prehospital, resuscitation, perioperative and intensive care situations. Often they are the fluid of choice in patients with uncontrolled haemorrhage both before blood transfusion and in conjunction with transfusion of packed cells. Unlike the dextran and starch solutions, so far they have been considered as having no significant effect on clotting mechanisms following studies based principally on clotting times. [1][2][3][4] While measuring whole blood coagulation times after in vitro dilution with colloids we noted a striking difference in clot quality compared with that seen with dilution using crystalloid. Our preliminary findings have been reported previously.5 In this article we describe more detailed investigations using clot weights, haematological analysis, thrombelastography and scanning electron microscopy, and include a description of the dose-response effect of varying degrees of dilution using regression analysis. Materials and methodsWherever fresh whole blood was used, care was taken to avoid prolonged venous stasis, venepuncture from the same site or delays in pipetting, and experiments were conducted under strict temperature control.CLOT WEIGHTS A total of 35 fresh whole blood samples were diluted to 15%, 30%, 45%, 60% and 75% with 0.9% sodium chloride and Ringer's solution (controls) or the test substances, 4% succinylated gelatin (Gelofusine, B. Braun (Medical) Ltd) and 3.5% polygeline solution (Haemaccel, Hoescht UK Ltd). After dividing each sample into test and control, the total volume of each sample after dilution was 5 ml. Clot weights were measured using the method described by Macfarlane.6 Because the clots would not adhere to a glass rod the test was modified by separating the clot from plasma on gauze in a funnel. Clots were weighed on an electronic balance and then examined physica...

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