Prescribing patterns of antibiotics and sensitivity patterns of common microorganisms in the Internal Medicine ward of a teaching hospital in Western Nepal: a prospective study

Background

Information about antibiotic use and resistance patterns of common microorganisms are lacking in hospitals in Western Nepal. Excessive and inappropriate use of antibiotics contributes to the development of bacterial resistance. The parameter: Defined daily dose/100 bed-days, provides an estimate of consumption of drugs among hospital in-patients. This study was carried out to collect relevant demographic information, antibiotic prescribing patterns and the common organisms isolated including their antibiotic sensitivity patterns.

Methods

The study was carried out over a 3-month period (01.04.2002 to 30.06.2002) at the Manipal Teaching Hospital, Western Nepal. The median number of days of hospitalization and mean ± SD cost of antibiotics prescribed during hospital stay were calculated. The use of antibiotics was classified for prophylaxis, bacteriologically proven infection or non-bacteriologically proven infection. Sensitivity patterns of the common organisms were determined. Defined daily dose/100 bed-days of the ten most commonly prescribed antibiotics were calculated.

Results

203 patients were prescribed antibiotics; 112 were male. Median duration of hospitalization was 5 days. 347 antibiotics were prescribed. The most common were ampicillin, amoxicillin, metronidazole, ciprofloxacin and benzylpenicillin. Mean ± SD cost of antibiotics was 16.5 ± 13.4 US$. Culture and sensitivity testing was carried out in 141 patients. The common organisms isolated were H. influenzae, E. coli, K. pneumoniae and S. aureus.

Conclusions

Antibiotic resistance is becoming a problem in the Internal Medicine ward. Formulation of a policy for hospital antibiotic use and an educational programme especially for junior doctors is required.     

Minimum amount of penicillin prophylaxis required to control Streptococcus pyogenes epidemic in closed community.

The prophylaxis required to control an epidemic of Streptococcus pyogenes throat infection in a junior detention centre has been reported. In a further epidemic an attempt was made to determine the minimum amount of penicillin required to control the outbreak. Oral penicillin (0.5 g) given as a single daily dose for 10 days to all boys after entry proved effective. The added risk of relatively deprived adolescent boys developing rheumatic fever is stressed.     

Famciclovir as antiviral prophylaxis in laser resurfacing procedures

Latent herpes simplex virus (HSV types I and II) may be reactivated by laser resurfacing procedures, presenting serious postoperative complications in approximately 9 percent of patients. Perioperative prophylactic administration of nucleoside analog antiviral agents has been shown to decrease the duration and severity of postsurgical herpes infection and to prevent recurrence. This study was conducted to assess the efficacy of famciclovir in preventing orofacial herpes virus reactivation and primary infection in patients undergoing laser resurfacing. HSV history was obtained from a total of 121 patients undergoing the procedure. Antiviral prophylaxis with famciclovir was begun 1 to 2 days before surgery and continued for 5 days after surgery. Patients with no history of orofacial herpes (n = 94) received 125 mg of famciclovir twice daily. Those with a history of orofacial herpes (n = 27) received 250 mg of famciclovir twice daily. Postsurgical HSV infection rates in patients receiving famciclovir prophylaxis were compared with those from a similar historical control group of HSV-positive patients (n = 127) who received no prophylaxis. In patients receiving famciclovir prophylaxis, one patient (1.1 percent) in the HSV-negative history group and no patients in the HSV-positive history group had postsurgical herpes infection. Famciclovir significantly reduced postsurgical herpes infection when compared with the 9.4 percent rate of herpes reactivation in patients who received no prophylaxis (p = 0.003). This study suggests that twice-daily famciclovir prophylaxis markedly reduces orofacial herpes virus infection in patients undergoing laser resurfacing.     

A trial of using augmentin (amoxicillin/clavulanate) in surgical practice]

The experience with the use of augmentin (amoxycillin/clavulane) in abdominal surgery for prophylaxis of postoperative purulent complications was analyzed. The drug was used in 44 patients after relatively pure operations, 37 of them having various risk factors. In 2 patients (4.5 per cent) of that group postoperative pyoinflammatory complications were recorded. For comparison the results of the prophylactic use of cefoperazone, cefamandole or ceftazidime in the group of 78 patients after relatively pure operations on the abdominal cavity organs were analyzed. Postoperative complications in the latter group amounted to 7.4 per cent (4 patients). The results of the treatment of patients in two groups after contaminated operations were also compared. The patients of one group (41 patients) were treated prophylactically with augmentin in a dose of 1200 mg intraoperatively followed by the drug use in a dose of 600 mg thrice daily for 1 to 2 days after the operation. Postoperative pyoinflammatory complications were recorded in 4 patients of that group (9.7 per cent). 78 patients of the other group were treated prophylactically with ceftazidime or cefoperazone in a dose of 2 g and metronidazole intraoperatively or cefoperazone in a dose of 2 g twice daily and metronidazole in a dose of 500 mg twice daily for 1 to 2 days after the operation. Postoperative infectious complications were recorded in 8 patients of that group (10 per cent). In the group of patients with acute cholecystitis treated with ciprofloxacin in a dose of 400 mg in combination, with metronidazole before the operation and for 1 to 2 days after the operation postoperative complications were recorded in 4 patients (17 per cent).     

Ciprofloxacin in the prevention and treatment of surgical infections]

A clinico-laboratory study on ciprofloxacin made by Bayer (Germany) was applied to patients with extended posttraumatic wounds and performed with the aim of preventing postoperative purulent complications in patients operated on the organs of the gastrointestinal tract. In the both groups ciprofloxacin was administered orally in doses of 500 and 1000 mg and intravenously in a dose of 200 mg. The results of the assay on ciprofloxacin sensitivity of the isolates from the wound excretion and urine showed that they were more sensitive to ciprofloxacin than to aminoglycosides and cephalosporins. 15 minutes after the intravenous administration the serum concentration of ciprofloxacin amounted to 7.5 +/- 0.9 micrograms/ml and in 6 hours it was equal to 0.45 +/- 0.45 micrograms/ml, the mean concentrations of ciprofloxacin being attained in the bile (8.7 +/- +/- 3.9 micrograms/ml), gallbladder wall (5.5 +/- 3.8 micrograms/g), liver (0.73 micrograms/g), muscles (1.93 micrograms/g) and tendon (0.15 microgram/g). After the oral administration in a dose of 500 mg ciprofloxacin was detected in the blood serum in an amount of 2.0 +/- 0.7 micrograms/ml in 1 hour and in an amount of 0.9 +/- 0.13 micrograms/ml in 6 hours. After the drug oral administration in a dose of 1000 mg the maximum concentrations were: 6.34 +/- 4.2 micrograms/ml on the average and 2.1 +/- 0.8 micrograms/ml in 6 hours (0.4 micrograms/g in the muscles, 1.4 micrograms/g in the skin and 0.34 micrograms/g in the bones). The study showed that ciprofloxacin was a highly efficient antimicrobial agent in the treatment of the complicated wound infections and the prophylaxis of the purulent complications during the postoperative period in the patients operated on gastrointestinal organs.     

Comparaison de deux modes de prophylaxie de l'infection urinaire chez l'enfant avec le triméthoprime--sulfaméthoxazole.

Two types of prophylaxis of urinary tract infection with trimethoprim-sulfamethoxazole (TMP-SMZ) were studied in 72 children with recurrent urinary tract infections or vesicoureteral reflux or both. Daily prophylaxis only was used in 36 children and thrice-weekly prophylaxis only in 25 others, and 11 children received successively both types of prophylaxis. The same dosage was used in all cases: 2 mg/kg of TMP and 10 mg/kg of SMZ, given at bedtime. With daily prophylaxis the infection rate over 556 patient-months was 5.4 cases per 1000 patient-months, compared with 285.4 cases in the year before prophylaxis; side effects were noted in 11% of the patients during treatment. With thrice-weekly prophylaxis the infection rate over 381 patient-months was 15.7 cases per 1000 patient-months, compared with 313.6 cases in the year before prophylaxis; only 3% of the patients receiving this treatment had a side effect that was possibly drug-related. These results indicate that effective prophylaxis of urinary tract infection in children can be obtained with these two types of treatment.     

A comparative evaluation of the pharmacokinetics of different forms of benzathine benzylpenicillin]

Comparative randomized opened pharmacokinetic evaluation of benzathine benzylpenicillin in three dosage forms was performed. Benzathine benzylpenicillin was used as extencilline (2.4 million U or 1.2 million U, "Rh?ne-Poulenc Rorer", France) and as bicillin-5 (1.5 million U, "Synthesis" Russia). 33 patients were included in investigation (23 women and 10 men aged 16-60 years). 25 persons had verified rheumatism without blood circulation failure signs, 4--had chronic tonsillitis and 4 were healthy volunteers. Benzylpenicillin concentration was estimated by microbiology test in blood samples taken at 1, 3, 24 hours and 7, 14 and 21 days after intramuscular drug injection. After 2.4 million U extencilline injection (12 patients) its concentration, was at the inhibition level for beta-hemolytic streptococcus group A (25 ng/ml) for 3 weeks-period in 83.3 per cent of patients. After 1.2 million U extencilline injection (10 patients) or 1.5 million U bicillin-5 injection (12 patients) the above mentioned concentration was achieved on the 21st day in 30 and 0 per cent of patients respectively. Thus the treatment with benzathine benzylpenicillin at the 1.2 million U dose in the form of extencilline or bicillin-5 doesn't provide adequate antistreptococcal concentration in blood in prolonged period and is not suitable for correct rheumatism prophylaxis in adult patients.     

In vitro activity of zidovudine alone and in combination with ciprofloxacin against Salmonella and Escherichia coli

Abstract The in vitro antibacterial activity of zidovudine alone and in combination with ciprofloxacin was investigated. Zidovudine showed a good activity against Escherichia coli and Salmonella (MIC range 0.5–8 μg/ml and 1.5–62 μg/ml respectively) isolated from biological samples of HIV-infected patients. These strains proved to be extremely susceptible to ciprofloxacin alone. The interaction between zidovudine and ciprofloxacin ranged from additive activity to indifference. No antagonism was observed: the FIC index for every combination resulted ≤1.5. The addition of AZT 1 mg/l (clinically achievable plasma concentration after therapeutic doses of 1200 mg/day) did not affect the bactericidal activity of ciprofloxacin; on the contrary, in some cases we observed an increase of bactericidal effect of the quinolone. These data have to be considered in patients with AIDS who can be treated concomitantly with zidovudine and ciprofloxacin.     

Effect of furosemide on the pharmacokinetics of benzylpenicillin and its penetration through the hematoencephalic barrier in experimental and clinical meningococcic meningitis]

Pharmacokinetics of sodium benzylpenicillin after intramuscular administration in a dose of 250 000 gamma/kg and simultaneous intramuscular injection of furosemid (lazix) in doses of 0.5--1--2 mg/kg was studied in experiments on a model of meningococcal meningitis of rabbits and in clinics on patients with meningococcal meningitis. A pronounced effect of furosemid on pharmacokinetics of benzylpenicillin as dependent on a number of factors was found. Furosemid and meningococcal endotoxin had a synergic effect and decreased benzylpenicillin excretion with urine resulting in prolongation of the antibiotic effect in the blood. An increase in benzylpenicillin blood levels and inflammation of the soft brain membranes increased permeability of the hemato-encephalic barrier for the antibiotic.     

Ciprofloxacin in the treatment of infections in oncology patients

Treatment of infectious complications with ciprofloxacin in 65 patients provided good and satisfactory results in 67.7 and 20.0 per cent of the cases, respectively. The drug was efficient in sepsis, urogenital infections, respiratory infections and postoperative purulent complications. Ciprofloxacin showed a broad antibacterial spectrum. 96.3 per cent of the isolates belonging to aerobic organisms causing purulent inflammatory processes, including those with high antibiotic resistance levels, such as Pseudomonas spp., Proteus spp., Klebsiella tribe and Staphylococcus aureus were sensitive to the drug. In its antibacterial spectrum ciprofloxacin was similar to ofloxacin. The advantage of ciprofloxacin is its possible use not only orally but also intravenously. Adverse reactions to ciprofloxacin were observed in 5 (7.7 per cent) out of the 65 patients. In two cases discontinuation of the drug use was required. The use of ciprofloxacin in treatment of infectious complications in oncological patients is promising.     

Prophylactic antibiotics in plastic and reconstructive surgery.

There is no consensus in the literature on the use of prophylactic antibiotics to prevent postoperative infection. This study was performed to investigate whether the use of prophylactic antibiotics has an effect on postoperative infection rates. A total of 1400 patients were classified into four groups based on their diagnosis. During the induction of anesthesia, half of each group received 2 g of a sulbactam-ampicillin combination and the other half received a placebo (saline solution) intravenously. Wound infection rates were observed in the postoperative period. Age, sex, and operative site of the patients with the same diagnosis were comparable in each group. The white blood cell count and the body temperature reading of each patient were recorded postoperatively. Wounds were observed daily in the postoperative period and graded according to a predetermined scale. Bacteriologic specimens were obtained from patients who had wound infections. According to our clinical experience, antibiotic prophylaxis is not necessary in plastic surgery. At the end of our 6-year study, a significant difference could not be found between the antibiotic prophylaxis and placebo groups.     

Comparative effectiveness of various antibiotics in the treatment of patients with meningococcal meningitis]

The results of treating 322 patients with various forms of meningococcal infection accepted to a hospital within a year are presented. The patients were divided into 3 groups by the character of etiotropic therapy. The patients of group I were treated with benzylpenicillin and those of group 2 were treated with levomycetin sodium succinate. Group 3 included the patients, the therapy of whom with the above two antibiotics failed and they were subjected to treatment with cefazolin, cefotaxime, amikacin and other broad spectrum antibiotics. Benzylpenicillin generally proved to be the drug of choice in the antibacterial therapy of meningococcal infection. In comparison to levomycetin (chloramphenicol) it provide more rapid clinical recovery of the patients and normalization of the indices of the cerebrospinal fluid. Only failure of benzylpenicillin therapy was considered as an indication to the broad-spectrum antibiotics to be in the complex treatment of the patients. As additional methods for estimating the efficacy of antibacterial therapy it was recommended to employ calculation of the integral indices of hemograms (the leukocyte index of intoxication and the hematologic index of intoxication).     

Primary infection of mice with high titer inoculum respiratory syncytial virus: characterization and response to antiviral therapy

Intranasal infection of BALB/c mice with respiratory syncytial virus (RSV)-A2 (0.5 x 10(8) - 2.0 x 10(8) plaque-forming units, PFU) produced disease characterized by weight loss (2-3 g) and mortality (60%-100%) with the mean day of death ranging from 6-7 d after infection. The extent of RSV disease was inoculum titer-dependent and required a replication competent virus. Lung titers of virus peaked at 0.5-1 x 10(6) PFU/g wet weight. Bronchoalveolar lavage fluid (BALF) levels of IL-1beta, TNF-alpha, INF-gamma IL-12, IL-6, MIP-1alpha, RANTES, and protein were elevated, whereas IL-2, IL-4, IL-5, IL-13, and IL-10 were unchanged. Histological assessment of lungs revealed marked inflammatory pathology characterized by bronchiolitis, vasculitis, and interstitial pneumonia. Whole-body plethysmography revealed significant disease-associated deficits of respiratory function. Therapy with ribavirin administered either by the intranasal, subcutaneous, or oral route significantly reduced disease in a dose-dependent manner. Delaying the initiation of therapy resulted in a loss of activity for ribavirin. Synagis administered either intramuscularly as a single dose in prophylaxis or intranasally in prophylaxis, followed by therapy, also significantly reduced disease in a dose-dependent manner. Infection of mice with a high titer inoculum of RSV-A2 resulted in severe and fatal pulmonary disease that was responsive to treatment. This model may be useful to characterize the in vivo activity of experimental therapies for RSV infection.     

Cefepime (maxipime) in the treatment of severe urinary tract infection]

Comparative susceptibility of microflora isolates from patients with complicated urinary tract infections to cefepime, other cephalosporins, amikacin, ciprofloxacin and ofloxacin was studied. Isolates in the diagnostic titers (5 x 10(4)-5 x 10(8)) from the patients treated with cefepime as etiotropic monotherapy were identified. The treatment course was 7 to 14 days. The daily dose was 1 to 2 g. The clinical and bacteriological efficacies of the cefepime therapy equaled to 93.2 and 85.4% respectively.     

Profit-sharing in health care institutions.

Zidovudine (AZT) is the first antiretroviral agent to be licensed for the treatment of human immunodeficiency virus (HIV) infection. Since the initial placebo-controlled trial showing improved survival among patients with acquired immunodeficiency syndrome (AIDS) or symptomatic HIV infection (AIDS-related complex [ARC]) zidovudine has been evaluated in other stages of HIV infection. This review offers physicians who treat patients with HIV infection a comprehensive analysis of the current data on the clinical efficacy of zidovudine in various stages of HIV infection and on zidovudine''s adverse effects. After a search of MEDLINE for pertinent articles published since 1985, controlled studies and studies of long-term zidovudine therapy, of zidovudine therapy for HIV-related conditions and of the incidence and management of adverse reactions were evaluated. In addition, abstracts from international meetings were reviewed. No significant difference in clinical outcome was found between high-dose and low-dose zidovudine therapy, but there were significantly fewer toxic effects in the low-dose group. In two other studies zidovudine was found to delay disease progression in patients with asymptomatic or mildly symptomatic HIV infection who had an absolute CD4 count of less than 0.5 x 10(9)/L; the low incidence of adverse reactions may have been due to either the early stage of the infection or the low dose used. The demonstration of zidovudine-resistant isolates after at least 6 months of therapy has yet to be correlated with clinical deterioration. When to begin zidovudine therapy among asymptomatic patients with a CD4 count of less than 0.5 x 10(9)/L remains unclear. Zidovudine can be used safely to delay progression to AIDS or ARC in certain patients with asymptomatic or mildly symptomatic HIV infection and can prolong survival in those with more severe infection. Further studies are necessary to identify indicators that could better define when to start treatment and how to alleviate toxic effects. Combination therapy with such agents as interferon alpha may become the preferred choice of therapy to prevent toxic effects and zidovudine resistance. Zidovudine prophylaxis has been used after HIV exposure. Although studies with animal models have had encouraging results infection has occurred despite immediate prophylaxis and thus further investigation is required.     

Ofloxacin efficacy in the prophylaxis and treatment of experimental plague due to antigen complete and defective strains of the pathogen]

Strains of the plague microbe, antigen complete and defective by fraction I and mouse toxin had the same in vitro susceptibility to ofloxacin (MIC 0.08 mg/L). The drug was superior in its activity to pefloxacin and especially nalidixic acid. In the experiments with albino mice (prophylaxis, 5 days) the ofloxacin efficacy was lower when the infection was due to the plague microbe strains deprived of the ability to produce fraction I and mouse toxin, evident from a statistically significant increase of the drug ED50 and a decrease of the animal survival percentage. When used in the doses corresponding to the human average daily doses, ofloxacin provided effective animal protection (80 to 100 per cent survival) after the prophylaxis for 7 days and the treatment of the plague infection irrespective of the strains, complete or antigen changed. However, when the infection is due to the antigen changed strain, ofloxacin should be used in the maximum daily doses at least for 7 days.     

Effect of the functional state of the internal organs on the pharmacokinetics of benzylpenicillin in angina]

The levels of benzylpenicillin on its intramuscular administration in doses of 100000 or 200000 units, as well as the renal and hepatic functions and the antibiotic binding by the host protein components were studied in 44 angina patients and 29 healthy persons. The benzylpenicillin levels were always markedly higher in the angina cases than those in the healthy persons. The ratio of the free and protein bound fractions of the antibiotic in the above groups was practically the same. At the same time the amount of benzylpenicillin excreted with the urine was higher in the angina patients than in the healthy persons approximately by 2 times. The study of the function of the internal organs revealed a marked decrease in the daily diuresis in all the angina patients and microhematuria in the 1/4 of the cases. The impairment of the renal function was determined by the laboratory methods practically in all the patients. On the basis of the data obtained it was concluded that the increased benzylpenicillin levels in the angina cases were connected with a decreased capacity for inactivating this substance by the liver enzymatic systems due to the changed function of this organ. The fact of the increased antibiotics levels in the host is considered as a positive phenomenon providing inhibition of the disease causative agents resistant to usual concentrations of the drug.     

On fluoroquinolones treatment safety in children (clinical, morphological and catamnesis data)]

Results of prospective comparative investigation of monofluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin) arthropathy are presented. The trial was performed at 144 children with mucoviscidosis (aged 0.5-16) and at 37 children with aplastic anemia (aged 1.75-15). Two groups differ by necessary antibacterials regimes and hence by different abilities for arthropathy development: patients with mucoviscidosis were treated with fluoroquinolones followed by repeated short courses in combination with other antibacterials; patients with aplastic anemia--were treated permanently for a long time with low doses as monotherapy for autoinfection prophylaxis. Analysis was performed on the base of catamnesis, year growth rate, postmortal morphological investigation of the right knee joint. It was shown that quinolone arthropathy development didn't depend on treatment duration, as it developed during the first three weeks of the fluoroquinolone use, but depended on the drug, patient age and nosology. Arthropathy has favourable prognosis and was fully resolved at the period from 7 days to 3 month according to the arthropathy form (arthrologic, arthritic). Quinolones arthropathy at the children has specific features, the main one is absence of cartilage damage confirmed by morphological analysis.     

Multiresidue analysis of fluoroquinolone antibiotics in chicken tissue using liquid chromatography-fluorescence-multiple mass spectrometry

An efficient liquid chromatographic method for the multiresidue analysis of fluoroquinolone antibiotics in chicken tissue has been developed in which quantitation using fluorescence and confirmation with multiple mass spectrometry (MS(n)) was achieved simultaneously. Using this method, eight fluoroquinolones were analyzed in fortified samples of chicken liver and muscle tissue with recoveries at levels of 10-200 ng/g generally in the range of 60-93%, except for desethylene ciprofloxacin, which consistently gave recoveries >or=45%. Relative standard deviations were excellent in all cases, and the limits of detection in ng/g were determined as follows in liver and (muscle): desethylene ciprofloxacin 0.3 (0.1), norfloxacin 1.2 (0.2), ciprofloxacin 2 (1.5), danofloxacin 0.2 (0.1), enrofloxacin 0.3 (0.2), orbifloxacin 1.5 (0.5), sarafloxacin 2 (0.6), difloxacin 0.3 (0.2). Confirmation of the identities of the fluoroquinolones was achieved by monitoring the ratios of two prominent product ions in MS(2) (desethylene ciprofloxacin) or MS(3) (all others). Levels of confirmation as related to ion ratio variability criteria were established. Enrofloxacin and ciprofloxacin were also determined in enrofloxacin incurred chicken liver and muscle using this method.     

Preoperative antibiotics and capsular contracture in augmentation mammaplasty

The main drawback with augmentation mammaplasty using implants is capsular contracture. The cause of this complication is still unknown. Silicone particles, hematoma, and bacterial contamination are some of the etiologic factors discussed. In this randomized, double-blind study on 76 breast-augmented women, 50 percent of the patients had preoperative prophylaxis with benzylpenicillin and dicloxacillin. Bacteria samples were taken intraoperatively. The number of negative cultures increased significantly with antibiotic prophylaxis. In four follow-ups during the first postoperative year, the rate of contractures was evaluated by subjective and objective methods. The results showed no statistically significant difference between the placebo and the antibiotic group with respect to the incidence of capsular contracture.