Latamoxef induced a severe coagulation disorder in older patients in China: Two case reports.

WHAT IS KNOWN AND OBJECTIVE: We present two cases of severe coagulation disorders induced by latamoxef, thereby revealing risk factors of coagulation disorder in latamoxef-treated patients. CASE SUMMARY: Two very elderly patients developed haemorrhage, and coagulation tests showed a longer prothrombin time (PT), activated partial thromboplastin time (APTT) and a high international normalized ratio (INR). Latamoxef was thought to be responsible for the coagulopathy in these patients, and coagulation disorder was relieved after vitamin-K intake. WHAT IS NEW AND CONCLUSION: We report on two cases of coagulopathy in patients given latamoxef. Advanced age, deficiency in vitamin-K intake, poor nutritional status, abnormal coagulation history, ongoing anti-coagulation/anti-aggregation therapy, renal dysfunction and polypharmacy are possible contributory factors, and should be looked out for when prescribing latamoxef.

Lysis-deficient bacteriophage therapy decreases endotoxin and inflammatory mediator release and improves survival in a murine peritonitis model.

BACKGROUND: Lysis-deficient (LyD) bacteriophages (phages) kill bacteria without endotoxin (Et) release. This may minimize systemic cytokine responses and limit inflammation in bacterial sepsis. We determined the effects of t amber A3 T4 LyD and virulent wild-type (WT) phages on mouse bacterial peritonitis. METHODS: Balb/c mice were injected with B40sul Escherichia coli, treated intraperitoneally with LyD, WT, or a beta-lactam antibiotic [latamoxef sodium (LMOX)], and followed for survival. We measured Et release, tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, as well as bacterial counts and peritoneal exudative cells (PECs) in peritoneal lavage fluid at 6 and 12 hours after infection. RESULTS: LyD mice showed significantly greater survival compared with other groups. Et levels were significantly lower in the LyD mice at 6 and 12 hours after infection. TNF-alpha and IL-6 levels were lower in LyD mice compared with control (untreated) mice at 12 hours. Compared with controls, bacteria counts in peritoneal lavage fluid were lower in all treatment groups (LyD, WT, or LMOX) at 6 and 12 hours. PEC counts were highest in LyD mice at 6 hours but significantly lower than that in WT phage- and LMOX-treated mice at 12 hours. CONCLUSIONS: LyD phage therapy significantly improves survival and attenuates the systemic effects of bacterial sepsis by minimizing Et release and pro-inflammatory mediators in murine bacterial peritonitis. Further studies may find phage therapy useful in treating peritonitis and multidrug-resistant bacterial infections.

Subclinical syphilitic hepatitis, which was markedly worsened by a Jarisch-Herxheimer reaction.

Early syphilitic hepatitis is uncommon and tends to be overlooked. However, the diagnosis of this disease is important, because appropriate treatment results in rapid resolution of the hepatitis. We report a case of subclinical early syphilitic hepatitis exaggerated by a Jarisch-Herxheimer reaction. This reaction helped to realize the diagnosis in this case.

Hemophagocytic syndrome associated with Bacteroides fragilis infection in a patient with acute monoblastic leukemia.

The HS has been associated with malignant hemopathies. We report here a case of HS related to Bacteroides fragilis during the course of acute monoblastic leukemia. Evolution was fatal despite remission of the leukemia process and response of the infection to appropriate antibiotic therapy.

[Two cases of Campylobacter fetus subsp. fetus sepsis].

We encountered two relatively rare cases of sepsis due to Campylobacter fetus subsp. fetus (C. fetus). Case 1. A 54-year-old female with abdominal polysurgery developed a slight fever and vomiting in August 1984. Despite the administration of some digestive drugs by her family doctor, these symptoms continued. In mid-October, she was hospitalized with high fever with chill and rigor on the skin. On the third hospital day, C. fetus was detected in the blood culture. After combination chemotherapy of intravenous drip infusion of latamoxef (LMOX) (2 g/day) and oral administration of erythromycin (EM) (800 mg/day), her symptoms improved. Case 2. A 57-year-old male with diabetic retinopathy and nephropathy was hospitalized because of slight fever, general edema and pleural effusion. On the 6th hospital day, C. fetus was detected in the blood culture and he was diagnosed with sepsis. Under treatment with the intravenous drip of LMOX (2 g/day) and oral administration of EM (1200 mg/day), his condition improved. Both cases had common underlying diseases such as hypoproteinemia with edema and problems in the lower intestinal tract; the former had polysurgery and malabsorption syndrome, the latter had diffuse ulceration of the colon. Such underlying conditions may have permitted the invasion of C. fetus into the blood.

Penetration of intravenous antibiotics into brain abscesses.

INTRA-ABSCESS CONCENTRATIONS OF the intravenously administered latamoxef (LMOX, moxalactam in the United States) and cefotetan (CTT), were studied in 11 patients with intracranial abscess. None of these patients underwent surgical ablation of the abscess. In all cases, the abscess was aspirated, and multiple aspirations were required in five patients. Antibiotic concentrations in 18 aspirates were, therefore, determined by the agar well method. LMOX concentrations in 16 aspirates drawn from nine brain abscess cases ranged from 0 to 10.9 micrograms/ml, with a mean (standard deviation) of 4.18 (3.04) micrograms/ml. The CTT concentration in one patient with a brain abscess was 8.51 micrograms/ml, and the LMOX concentration in the one remaining patient with subdural empyema was 5.20 micrograms/ml. In one patient, the serum-to-pus penetration rate of LMOX was estimated to be 0.11 against the peak value of the concentration in serum or 0.44 against the simultaneously obtained level in serum. Significantly higher concentrations of LMOX were produced in abscess cavities with multiple-dose administration or by prior drainage of pus. More-advanced stages of local inflammation, as demonstrated by computed tomography, correlated with higher concentrations. However, the routine indexes of systemic inflammation, such as body temperature, white blood cell count, and level of C-reactive protein in serum, cannot be used to predict the concentration present in intracerebral pus. A tendency for LMOX concentrations in pus obtained after single dose-administration to decrease with increasing duration from symptom onset to sampling was observed but was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Mortality rate and bacteremia, endotoxin, and endothelin-1 levels in antibiotic therapy for E. coli septic peritonitis.

In order to study the mortality rate and bacteremia, plasma endotoxin, and plasma endothelin-1 levels in antibiotic therapy for E. coli peritonitis, blood samples were obtained from rats given intraperitoneal injections of latamoxef or placebo. Intraperitoneal injections of latamoxef improved the prognosis of peritonitis rats. Two h after treatment, bacteremia levels were noticeably higher in rats treated with placebo than in rats treated with latamoxef, but the latamoxef-treated group manifested a significant elevation of plasma endotoxin and endothelin-1 levels compared to the placebo-treated group. The results of this study demonstrate that treating E. coli septic peritonitis with selected antibiotics induces increased plasma endotoxin levels, which are associated with elevation of plasma endothelin-1 levels.

Ceftriaxone versus latamoxef in febrile neutropenic patients: empirical monotherapy in patients with solid tumours.

121 patients with 132 febrile episodes were randomised to ceftriaxone or latamoxef monotherapy in order to compare antibiotic efficacy in neutropenic patients treated with cytotoxic chemotherapy for solid tumours. In 80 evaluable episodes no significant differences were observed between the two groups with respect to efficacy and fatal failure rates. Of episodes treated with ceftriaxone, 67% showed a favourable clinical response vs. 61% in the latamoxef group. The clinical response rates in episodes with documented bacterial infections were 67 and 56% in the two treatment groups. In 18% of the episodes with documented initial infections the patients died of presumably uncontrolled infection. The convenient once daily dosage schedule combined with fewer severe adverse reactions favours the use of ceftriaxone instead of latamoxef. Although a relative high degree of response was seen, empirical antibiotic monotherapy apparently does not offer a sufficient antibacterial cover in infections in this type of patient with defective host immunity.

Protective effect of a cephalosporin, Shiomarin, plus a new potent protease inhibitor, E3123, on rat taurocholate-induced pancreatitis.

The role of infectious factors in the pathogenesis of acute pancreatitis and the protective effect of combined therapy with a new potent synthetic protease inhibitor, E3123, and a new potent synthetic cephalosporin, Shiomarin were examined in rat acute pancreatitis. Sodium taurocholate injection into the pancreatico-biliary duct of rats caused severe pancreatitis with a high mortality rate, characterized by hyperamylasaemia, high amylase activity in ascitic fluid, hyperendotoxaemia and a high serum level of fibrin degradation products (FDP) and redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction. Sodium taurocholate injection into the pancreatico-biliary duct also caused the bacterial growth in the pancreas. In rats with E3123 infusion almost all parameters were improved, including mortality rate, serum and ascitic fluid amylase levels, plasma endotoxin and serum FDP levels, and distribution of lysosomal enzyme. But combination therapy with E3123 and Shiomarin was significantly more protective than E3123 therapy alone. These results indicate that infection plays an important role in the development of severe pancreatitis and that combination therapy with a new synthetic protease inhibitor and a new potent antibiotic may be useful in the treatment of severe pancreatitis.

[A case of hematuria associated with cefem group antibiotics].

The patient was a 76-year-old male with disturbance of consciousness due to cerebral infarction. He was found lying in his garden on July 30, 1990 and was immediately hospitalized. Central venous alimentation was started on the same day, because the patient was incapable of oral nutritional intake. Aspiration pneumonia developed on August 3. As Pseudomonas aeruginosa and Candida were detected by sputum cultures on August 20, antibiotics were changed to latamoxef (LMOX), 6 g/day, tobramycin, 180 mg/day, and fluconazole, 200 mg/day, from August 30. Macroscopic hematuria was noted after exchange of the urethral catheter. Hematuria gradually worsened, bladder tamponade occurred, and anemia had exacerbated with Hb decreasing from 13.4 to 8.7 g/dl and Hct from 39.1 to 26% on September 14, when the patient was referred to our department. Corresponding marked increases were observed in PT from 11.5 to 50.1 seconds and in APTT from 33.7 to 107.6 seconds. As the hematuria was suspected to be due to vitamin K deficiency hypoprothrombinemia induced by LMOX, its administration was discontinued on the day of the referral. Hematuria was alleviated from the next day, and PT normalized to 12.1 seconds and APTT to 36.6 seconds 3 days after discontinuation. The administration of vitamin K was started on this day, and hematuria disappeared 7 days after discontinuation of LMOX administration.

Diffusion of cefmenoxime and latamoxef into prostatic fluid in the patients with acute bacterial prostatitis.

Twenty-two patients with acute bacterial prostatitis were treated with cefmenoxime (CMX) or latamoxef (LMOX), which have susceptibilities against various gram-negative bacteria. First 11 patients received a 5- to 12-day course of cefmenoxime and the next 11 received a 6- to 13-day course of latamoxef. All patients were treated successfully except 1 patient with a drug allergy. Diffusion of CMX or LMOX into prostatic fluid in these patients and healthy controls were evaluated. The mean value of CMX in the expressed prostatic fluid was 12.8 micrograms/ml in the patients receiving 2 g of CMX intravenously and 0.7 micrograms/ml in the controls. The mean value of LMOX was 14.0 micrograms/ml in the patients receiving 2 g of LMOX intravenously and 1.2 micrograms/ml in the controls. The diffusion of CMX and LMOX into prostatic fluid in the patients with acute bacterial prostatitis was strikingly higher than that of controls.

A randomized trial comparing imipenem/cilastatine alone with latamoxef plus tobramycin in febrile neutropenic patients with lung cancer.

We conducted a randomized trial to compare the efficacy of imipenem/cilastatine (IPM/CS) monotherapy with that of a combination of latamoxef (LMOX) and tobramycin (TOB) in the initial management of fever and neutropenia in patients with lung cancer. Leukocytopenic febrile patients (less than 3,000 leukocytes per microliters; temperature greater than 38 degrees C) with lung cancer given induction therapy were randomly assigned to receive intravenous treatment with either 1 g IPM/CS twice daily or 2 g LMOX plus 90 mg TOB twice daily. A total 101 febrile episodes were studied. Fifty-one episodes were treated with IPM/CS and 50 with LMOX+TOB. Fifty-nine of the febrile episodes were bacteriologically confirmed, while an organism could not be isolated despite the presence of obvious clinical infection in the remaining 42. The response rate was 82% with IPM/CS and 80% with combination therapy. This difference was not statistically significant. The response rate regarding gram-negative infections was 10 out of 14 (71%) in the IPM/CS group and seven out of 12 (58%) in the LMOX+TOB group. This difference was also not significant (P = 0.484). The response rate in severely neutropenic patients (neutrophils less than 100/microliters) was low (P = 0.078). Three patients in the IPM/CS group were withdrawn from the study due to skin rash and vomiting. Therapy with IPM/CS monotherapy was as effective as a combination regimen.

Control of infection due to Klebsiella pneumoniae in an intensive care nursery.

Because of an increased incidence of necrotizing enterocolitis (NEC) temporally related to Klebsiella pneumoniae colonization noted in several infants, a study was undertaken to identify the source and to eradicate the infection. Twenty infants in the neonatal intensive care unit (NICU) and 51 in the well-baby nursery were prospectively studied. Cultures were done on all infants. In addition, cultures were done on all employees and parents who regularly visited. Our results showed an increased incidence of infection during this period--8.3% as compared with 4.79% overall. Colonization with K pneumoniae was eradicated, at least temporarily, by establishing a cohort system in both the NICU and the well-baby nursery and by the administration of antibiotics to all infants in these nurseries. Colonized parents and employees were also treated. Follow-up cultures showed clearing of Klebsiella, and the cohort system was abolished. Serotyping of all affected infants later showed that different strains were present, making it unlikely that there was a common source for the Klebsiella. (Initially the source of infection had been thought to be a mother whose premature triplets were colonized. We feel that the eradication of this organism and the subsequent decline in NEC was enhanced by the combination of cohorting and handwashing. The selected use of antibiotics may have prevented an extension of the outbreak, but this could not be proven.

Single dose prophylaxis in colorectal surgery.

Moxalactam disodium (Latamoxef), was evaluated as a single dose prophylactic antibiotic against wound infection in open colorectal surgery. One hundred and five consecutive patients admitted to the university department of surgery, Wellington Hospital, were studied. Twelve patients were excluded because either the antibiotic was not given or antibiotics were given for other reasons. Eleven patients developed early wound infections and one further patient developed a late infection, an overall wound infection rate of 13% (95% CI 7-19). Whilst this infection rate is higher than that previously reported from this unit using more prolonged (3 dose) antibiotic prophylaxis (9.8%, 95% CI 9.6-10) the difference is not likely to be significant because the patient groups were not matched, and the comparisons were sequential. On the basis of the present study it is concluded that 1 g of moxalactam disodium administered at the induction of anaesthesia in open colorectal surgery is inexpensive, is associated with a low incidence of side effects and its further use in colorectal surgery would seem to be justified.

Campylobacter fetus subspecies fetus meningitis with chronic alcoholism and diabetes mellitus.

A case of Campylobacter fetus subspecies fetus meningitis is reported. The patient had underlying diseases, namely chronic alcoholism and diabetes mellitus. The infection did not respond to Piperacillin and Cefotaxime, but did respond to Ampicillin and Moxalactam. The patient was discharged on the 33rd hospital day showing no neurological deficit complications, and has remained free of recurrent disease for one month after the discontinuation of therapy.