PREVENTION OF WOUND INFECTION IN ELECTIVE COLORECTAL RESECTIONS BY PREOPERATIVE CEPHAZOLIN WITH AND WITHOUT METRONIDAZOLE

Fifty patients were admitted to a prospective controlled double blind trial for assessment of the effect of preoperative intramuscular cephazolin with oral metronidazole or placebo on the incidence of wound infection in patients requiring treatment by elective large intestinal resection. All patients were operated upon by one surgeon. After exclusion of two patients who died postoperatively 48 were analysed. No wound infection occurred In 22 patients receiving cephazolin with metronidazole. One (3.8%) infection developed in 26 patients receiving cephazolin with placebo. The difference did not attain statistical significance. Preoperative intramuscular cephazolin with or without metronidazole provides an effective and safe method of chemoprophylaxis for elective colorectal resection.     

Preventing and treating discitis: cephazolin penetration in ovine lumbar intervertebral disc

Infection can occur after any spinal procedure that violates the disc and although it is not common, the potential consequences are serious. Treatment of discitis is not always successful and the key to management is prevention. Intradiscal prophylaxis with antibiotic is routinely used in spinal surgery, but there is a limited understanding of how well antibiotics can enter the avascular disc after intravenous injection. An in vivo ovine study to optimise prophylactic and parenteral treatment of discitis is described to assess the effectiveness of cephazolin in preventing and treating infection. The concentration of cephazolin was measured in disc tissue from normal and degenerate sheep discs to determine if cephazolin can enter the disc and if disc degeneration affects antibiotic uptake. Fourteen sheep were deliberately inoculated with bacteria to induce discitis. Eight sheep (“prophylaxis” group) were given either a 0, 1, 2 or 3 g dose of prophylactic cephazolin before inoculation while the remaining sheep (“treatment” group) were treated with cephazolin commencing 7 days after inoculation for 21 days at a dose of 50 mg/kg/day. Histopathology and radiography were used to assess the effect of the different treatments. Cephazolin was given 30 min prior to sacrifice and the intradiscal concentration was measured by biochemistry. In the “prophylaxis” group all doses of antibiotic provided some protection against infection, although it was not dose dependent. In the “treatment” group discitis was confirmed radiologically and histologically in all animals from 2 weeks onwards. Biochemical assay confirmed that antibiotic is distributed throughout the disc but was present in higher concentration in the anulus fibrosus than the nucleus pulposus. This study demonstrated that whilst the incidence of iatrogenic discitis can be reduced by antibiotic prophylaxis, it could not be abolished in all incidences with a broad-spectrum antibiotic such as cephazolin. Furthermore, antibiotics were ineffective at preventing endplate destruction once an intradiscal inoculum was established.Declaration: The experiments comply with the current laws of Australia including ethics approval for the use of animals in research. Ethical approval was obtained for all animal studies from the Animal Ethics Committee, Veterinary Research Division of the Institute of Medical and Veterinary Science.     

A comparison of nalbuphine with morphine for post-orchidopexy pain

A double-blind investigation was conducted to compare nalbuphine with morphine for the control of pain after unilateral orchidopexy. Fifty boys under 11 years of age were allocated randomly to receive intramuscular nalbuphine 0.2 mgkg-1 or morphine 0.2 mgkg-1 immediately after induction of anaesthesia. Pain was assessed on a three-point scale, 1, 2 and 4 h after injection and on the morning following operation. Side-effects were also recorded. There were no significant differences between the two drugs in either the provision of analgesia, or the incidence of the principal side-effects of vomiting and sweating. There was a high incidence of vomiting in both groups. Nalbuphine is a satisfactory alternative to morphine for post-orchidopexy pain and may offer the advantages of greater safety and convenience.     

Comparison of cefixime and co-trimoxazole in acute uncomplicated urinary tract infection. A double-blind general practice study

Five hundred and twenty-eight patients with presumptive acute uncomplicated urinary tract infection (UTI) were randomly assigned to receive cefixime 400 mg once daily, cefixime 200 mg twice daily or co-trimoxazole 2 tablets twice a day for 10 days; 477 completed at least 5 days of therapy. Of the patients 342 (65%) had positive baseline urine cultures, yielding 353 pathogens. A microbiological response was determined for 280 pathogens (79%), eradication being observed in over 94% of isolates; 153 pathogens (43%) were sensitive to both cefixime and co-trimoxazole and eradication was observed in over 96% of cases. Clinical response correlated well with microbiological response. The incidence of diarrhoea and stool changes was higher (P less than 0.005) in the patients who received cefixime once daily than in the other groups. There was a significantly higher incidence of stool changes with cefixime twice daily than with co-trimoxazole (P less than 0.05), but these did not necessitate discontinuation of therapy. Nausea was commoner with co-trimoxazole (P less than 0.05). The majority of pathogens isolated were Escherichia coli, Proteus mirabilis and staphylococci. Approximately 24% of E. coli were resistant in vitro to co-trimoxazole (P less than 0.005). Cefixime 200 mg twice daily is an effective and safe alternative to co-trimoxazole in the management of acute uncomplicated UTI.     

Co-trimoxazole prophylaxis for children who are HIV-exposed and uninfected: a systematic review

Introduction

Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale-up of maternal antiretroviral therapy, most children remain HIV-exposed uninfected (HEU) and the benefits of universal co-trimoxazole are uncertain. We assessed the effect of co-trimoxazole on mortality and morbidity of children who are HEU.

Methods

We performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa-Wide Information, SciELO and WHO Global Index Medicus for peer-reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co-trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity.

Results

We screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co-trimoxazole prophylaxis started at 2–6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub-studies found that antimicrobial resistance was higher in infants receiving co-trimoxazole. Two trials in Uganda investigating prolonged co-trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence.

Discussion

Studies show no clinical benefit of co-trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co-trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non-malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings.

Conclusions

In low-mortality settings with few HIV transmissions and well-performing early infant diagnosis and treatment programmes, universal co-trimoxazole may not be required.     

Discitis after discography. The role of prophylactic antibiotics

Discitis after discography is due to bacterial penetration into the intervertebral disc by a contaminated needle and has an incidence of 1% to 4%. We have examined the prophylactic role of cephazolin administered at the time of discography. An experimental study in sheep using radiographic contrast containing Staphylococcus epidermidis showed that either adding the antibiotic to the intradiscal suspension or giving it intravenously 30 minutes before intradiscal inoculation of bacteria prevented any radiographic, macroscopic or histological signs of discitis; all the intervertebral disc cultures were negative. In a prospective clinical study of 127 consecutive patients having lumbar discography, the injected contrast contained cephazolin 1 mg per ml. None of the patients developed clinical or radiographic signs of discitis. We recommend the use of a suitable broad spectrum antibiotic in a single prophylactic dose whenever the intervertebral disc is entered.     

Antibiotic penetration into rabbit nucleus pulposus with discitis

Objective

To assess the penetration into nucleus pulposus (NP) of cephazolin and clindamycin in a discitis model.

Materials and methods

Twenty New Zealand white rabbits were inoculated with 103 Staphylococcus aureus at lumbar disc space. The rabbits with discitis confirmed by MRI 10 days after inoculation were divided into two groups. One was given cephazolin by intravenous (IV) at 80 mg/kg/day at 1.5 h interval for 5 half-lives; the other was given clindamycin by IV at 30 mg/kg/day at 2.5-h interval for 5 half-lives. Thirty minutes after completion of the last dose, NP and serum were sent to measure antibiotic concentration.

Results

Two rabbits died during inoculation. After 10 days, 18 rabbits were confirmed discitis in the inoculated levels. The cephazolin and clindamycin can diffuse throughout the infected, sham-infected and normal NP. The serum concentration of cephazolin and clindamycin was 251.3 ± 40.5 and 21.6 ± 4.71 mg/l, respectively. The cephazolin concentration in infected NP (1.93 ± 0.84 mg/l) was higher than that in sham-infected (1.73 ± 0.61 mg/l) and normal NP (1.68 ± 0.65 mg/l), but the difference showed no statistically significant (P > 0.05). The cephazolin penetration into NP averaged 0.68–0.77 % of serum level. The clindamycin concentration in infected NP (4.32 ± 1.54 mg/l) was higher than that in sham-infected NP (2.63 ± 1.26 mg/l) and normal NP (2.59 ± 1.01 mg/l) (P < 0.05). The penetration into NP averaged 11.9–20 % of serum level. There was no significance difference between sham-infected and normal NP in clindamycin and cephazolin concentration (P > 0.05).

Conclusions

This study demonstrates cephazolin and clindamycin can penetrate the infected and normal NP. The antibiotics charge influences the delivery. Furthermore, infection condition selectively promotes antibiotic distribution within NP.     

Digoxin and Propranolol in the Prophylaxis of Supraventricular Tachydysrhythmias after Coronary Artery Bypass Surgery

Supraventricular tachydysrhythmia is a bothersome and potentially harmful occurrence after coronary artery bypass graft operation (CABG). Use of digoxin prophylaxis preoperatively has yielded conflicting results in lowering the incidence of supraventricular tachydysrhythmia. In this study, three groups of patients were formed. Group 1 served as the control; no prophylactic medication was given. Group 2 was given digoxin prophylaxis beginning immediately after operation. Group 3 received digoxin postoperatively as did Group 2, plus orally administered propranolol beginning on postoperative day 2.No difference in the incidence of supraventricular tachydysrhythmia was found between Groups 1 and 2 (28.2% versus 28.9%). However, the incidence in Group 3 was 2.2%, and this represented a statistically significant difference (p < 0.005) compared with either Group 1 or 2. The combined use of digoxin and propranolol postoperatively significantly reduced the incidence of supraventricular tachydysrhythmia after CABG.     

A comparative study of techniques of postoperative analgesia following caesarean section and lower abdominal surgery

A double-blind, within-patient trial was carried out to compare intramuscular pethidine 100 mg, epidural pethidine 50 mg and epidural bupivacaine 25 mg for pain relief on the day after caesarean section or lower abdominal gynaecological surgery. Analgesia was assessed on a visual analogue pain scale. Forced expiratory volume in one second (FEV 1.0) and venous plasma catecholamine levels were measured immediately before and approximately thirty minutes after each treatment. At the completion of the study the treatments were ranked in order of patient preference. Nineteen patients completed the trial. Analgesia provided by epidural pethidine 50 mg was superior to intramuscular pethidine 100 mg (p less than 0.05) but not statistically better than epidural bupivacaine. There was no significant difference in the duration of analgesia between the active treatments. A mean increase in FEV 1.0 of 18% occurred after both of the epidural treatments, but this did not achieve statistical significance. There was no significant change in catecholamine levels after any of the treatments. Epidural pethidine was preferred by patients over and above intramuscular pethidine and epidural bupivacaine (p less than 0.05).     

Co-trimoxazole and trimethoprim in complicated urinary tract infection

Previous work has suggested that co-trimoxazole may be superior to trimethoprim in the treatment of complicated urinary tract infection. A prospective study has been done to assess the relative value of the drugs in this situation using trimethoprim at higher than normal dosage. Fifty three patients (33 women and 20 men) were randomly allocated to either a fourteen-day course of co-trimoxazole tabs, 2 twice a day (27 patients) or trimethoprim 250 mg twice a day (26 patients). After patient withdrawals from the study, 17 (77%) of the co-trimoxazole group achieved a sterile urine three weeks after starting treatment compared with 15 (65%) in the trimethoprim group (X2 = 0.80). When those patients with sterile urine at three weeks who could be reassessed four weeks later were analyzed, 8 (89%) of the co-trimoxazole patients maintained a sterile urine against 7 (58%) in the trimethoprim group (X2 = 1.09). Although statistical significance was not attained, the results suggest that even at increased dosage, trimethoprim would not appear to be as efficient as co-trimoxazole in complicated urinary tract infection.     

A microbiological study of acute otitis media in Bloemfontein

Tympanocentesis was done on 36 patients (57 ears) with acute otitis media. Positive cultures were obtained in 65% of cases. Streptococcus pneumoniae was the most commonly isolated organism (25% of ears). There was a high incidence of Staphylococcus epidermidis infection (14% of ears); these organisms are considered to be true pathogens. Haemophilus influenzae seemed to be less common than in other series and in all our cases were non-producers of beta-lactamase. Penicillin and amoxycillin appeared to be equally effective and there seemed to be little difference between responses to cefaclor, erythromycin and co-trimoxazole.     

Intrathecal addition of morphine to bupivacaine is not the cause of postoperative nausea and vomiting

Background and Objectives. Postoperative nausea and vomiting after anesthesia is an distressing side effect. This study was undertaken to determine to what extent spinal opioids contribute to postoperative nausea and vomiting (PONV) and secondly to how effectively metoclopramide can reduce the incidence of PONV after intrathecal administration of morphine. Methods. Patients were allocated to three groups all undergoing major joint surgery of the lower limb. In group 1 (n = 200), intrathecal anesthesia was assessed by administration of 20 mg bupivacaïne and 0.2 mg morphine. In Group 2 (n = 100) intrathecal anesthesia was assessed in the same way and in addition, 20 mg metoclopramide intramuscular during maintenence of anesthesia and a second dose of 20 mg metoclopramide was administered intramuscular after arrival at the recovery room. Finally, in group 3 (n = 100), intrathecal anesthesia was assessed after administration of 20 mg bupivacaïne. Results. The maximum PONV percentages were 41.1%, 32.7%, and 37% in groups 1, 2, and 3, respectively. The consumption of antiemetics was similar in all groups. The number of patients who needed one or more additional antiemetics during the first 24 hours after surgery was 112 (56.6%), 57 (58%), and 60 (60%) in groups 1, 2, and 3, respectively. Conclusions. Administration of metoclopramide did not reduce the overall incidence of PONV. Our study shows no relationship between the use of intrathecal morphine and the incidence of PONV during the first 24 hours postoperative.     

Fluid deprivation before operation

The effect of oral fluids before operation, followed by intramuscular morphine, on gastric volume and pH was examined in 150 elective surgical patients, ASA physical status 1 and 2, who were randomly assigned to one of the three groups of 50 each. Group 1 (control) continued their overnight fast; patients in Groups 2 and 3 received 150 ml water 2 hours before the scheduled time of surgery. Patients in Group 3 received intramuscular morphine 0.15 mg/kg and promethazine 0.5 mg/kg one hour before operation. The residual gastric volume was obtained by suction and its volume and pH measured immediately after induction of anaesthesia. Statistically significant (p less than 0.05) decrease in residual gastric volume was observed in Groups 2 and 3 as compared to Group 1. However, the difference between these two groups was not statistically significant. There was no statistically significant difference in pH among the three groups. Overnight fluid fasting is not justified in elective surgical patients. Morphine can be safely given one hour before surgery in patients who have received water (150 ml) 2 hours before operation.     

Treatment of peritonitis in continuous ambulatory peritoneal dialysis patients with co-trimoxazole

Peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) represents the most frequent and difficult problem related to this new form of treatment of ESRD patients. Various treatments have been reported previously. The aim of this study was to investigate the efficiency of a standardized initial treatment in 45 episodes of peritonitis. This was designed to be rapidly efficient, devoided of side-effects and easy enough to be performed by the patients themselves. When peritonitis was clinically suspected, patients received intraperitoneal co-trimoxazole (80 mg trimethoprim, 400 mg sulfamethoxazole), in each of the four daily bags concomitantly with 1,000 U heparin during 2 weeks and half of this dose during 2 other weeks. Our results demonstrate that 88% of the isolates were sensitive to co-trimoxazole and 85% of the patients completed this treatment. All were cured and no relapses were observed. Only 18 days of hospitalisation were required in the 45 episodes of peritonitis. Another anti-infective agent was used in 3 cases of gram-negative peritonitis and 4 other initially resistant to co-trimoxazole. It is concluded that initial treatment of CAPD peritonitis with co-trimoxazole is justified by the high proportion of sensitive germs and that it represents a safe, efficient and inexpensive treatment.     

Ropivacaine myotoxicity after single intramuscular injection in rats

BACKGROUND AND OBJECTIVE: We conducted this study in order to evaluate the potential myotoxic effects of ropivacaine after single injection in rats and the time-course of the possible damage. METHODS: One hundred and twenty-eight male Wistar rats were allocated to four different groups. The first three groups received intramuscular injections with ropivacaine 0.75%, ropivacaine 0.5% and normal saline, respectively, into the right tibialis anterior muscle. The fourth group received needle puncture without injection. Eight rats from each group were sacrificed 2, 4, 7 and 30 days after injection. Samples were blindly examined under light microscope for evidence of myotoxicity, scored as 0 = no damage to 3 = myonecrosis and statistically analysed. Samples obtained 7 days after injection were also examined under transmission electron microscope. RESULTS: Ropivacaine 0.75% and ropivacaine 0.5% caused extensive destruction to muscles fibres, compared to saline or needle on days 2, 4 and 7. Statistically significant differences were found in muscle damage by drug injections among all groups except for saline vs. needle groups. Thirty days after injections all sample appearances had returned to normal. CONCLUSIONS: Ropivacaine after single intramuscular injection caused reversible muscle damage in a dose-dependent manner.     

Clinical relevance of single administration of prophylactic antimicrobial agents against febrile events after removal of ureteral stents for patients with urinary diversion or reconstruction

Objective: To assess the efficacy of antimicrobial prophylaxis when removing ureteral stents after urinary diversion or reconstruction and to establish the most appropriate prophylactic protocol to prevent febrile events. Methods: We retrospectively investigated the incidence of febrile events in the two studies. Study 1 consisted of 39 patients who received antimicrobial prophylaxis and 31 who did not. Study 2 included 48 patients who were given oral fluoroquinolone (FQ) and 27 who had intramuscular injection of an aminoglycoside (AG). Results: In study 1, the incidence of febrile events was significantly lower in patients receiving antimicrobial prophylaxis (26.0%) than in those not receiving it (51.6%) (P = 0.025, χ² test). In study 2 there was a 13% incidence of febrile events, which was much lower than the incidence found in study 1. The incidence of these events was similar between the two study groups, being 13% for those receiving FQ and 15% for those receiving AG. Conclusions: Prophylactic administration of antimicrobials reduces the incidence of febrile events after removal of ureteral stents. Both FQ and the AG are equally effective in this setting.     

The stone heart. Development of a canine model, with ultrastructural survey and metabolic manipulation

A reproducible canine model of stone heart (irreversible left ventricular rigor) is described. During the studies, perfusion of the coronary circulation with various concentrations and compositions of magnesium sulfate solutions did not significantly influence the development of stone heart. Approximately 90 minutes of normothermic, ischemic arrest appeared to be the turning point for the transition of left ventricles from a flaccid state to one of rigor. In spite of left ventricular rigor, right ventricles remained flaccid and could be defibrillated.Ultrastructural studies showed that mitochondria were destroyed in left ventricles in rigor while right ventricular mitochondria were preserved even after two hours of normothermic, ischemic arrest. In either ventricle, glycogen granules were dissipated after two hours. The increased incidence of left ventricular rigor after two hours of normothermic, ischemic arrest compared with one hour of ischemic arrest was highly significant.     

Iatrogenic discitis: the role of intravenous antibiotics in prevention and treatment. An experimental study

The role of antibiotics in the treatment of iatrogenic discitis remains controversial. This study was carried out to assess the ability of cephazolin (a first-generation cephalosporin) to penetrate the intervertebral disc and to establish the role of intravenous antibiotics in the prevention and treatment of iatrogenic discitis. Six sheep had 1 g of intravenous antibiotic administered between 30 minutes and 120 minutes before being killed. Two adjacent lumbar intervertebral discs were harvested and assayed for antibiotic concentration. Cephazolin could only be detected in the animals killed at 30 minutes. Intravenous cephazolin was administered 30 minutes before bacterial inoculation in 46 discs of nine sheep. In five animals, the bacterial suspension contained radiographic contrast and, in four sheep, reconstituted chymopapain. No evidence of discitis was found at any level at death. Eight sheep were treated with intravenous cephazolin commencing 1, 2, or 3 weeks after bacterial intradiscal inoculation and for periods of up to 21 days. All discs developed discitis, and the lesions appeared to be similar, irrespective of time between inoculation and the commencement, duration, and dosage of antibiotic therapy. Our study supports the use of a suitable broad-spectrum antibiotic during any surgical procedure that invades the intervertebral disc. Antibiotics, however, are unable to arrest the progression of discitis once it is established     

A comparison of rectal diclofenac with intramuscular papaveretum or placebo for pain relief following tonsillectomy

A controlled investigation was conducted to compare the effectiveness of diclofenac and papaveretum in the prevention of pain and restlessness after tonsillectomy in children. Sixty children between 3 and 13 years of age were randomly allocated to receive rectal diclofenac 2 mg/kg, intramuscular papaveretum 0.2 mg/kg or no medication immediately after induction of anaesthesia. Pain and appearance were assessed 1, 3 and 6 hours postoperatively, and the following morning. The assessments were double-blind and performed by the same observer. No significant differences in postoperative pain were found between the groups at any time. The use of diclofenac was associated with a significantly more rapid return to calm wakefulness and had significantly less effect upon respiratory rate. Consumption of paracetamol on the day of operation was significantly less in the diclofenac group. Diclofenac may offer advantages compared to papaveretum with regard to safety and convenience for use in the treatment of pain after tonsillectomy in children.     

The effect of premedication on the incidence of postoperative vomiting in children after E.N.T. surgery

The influence of premedication and intraoperative narcotic administration on the incidence of vomiting after E.N.T. surgery was studied over a six-month period in 596 children. A high incidence of vomiting was found after intramuscular papaveretum and hyoscine and after oral diazepam. Oral trimeprazine tartrate was associated with a low incidence of vomiting and was found to have an anti-emetic effect when an opiate analgesic was administered after induction of anaesthesia.