Combinations of Antibiotics

PEDIATRICS ◽  
1960 ◽  
Vol 26 (3) ◽  
pp. 498-499
Author(s):  
Ernest Jawetz

I read with interest the paper by Haggerty and Ziai (Pediatrics, 25:742, 1960). I fully agree with the authors' recommendation that acute bacterial meningitis of infants be treated with multiple drugs directed at the most likely etiologic agents until a specific single organism has been identified. However, the authors' repeated references to some of my past publications force me to call attention to some possibly misleading statements in their paper. After the initial demonstration of "antibiotic antagonism" in vitro and in experimental animals, we pointed out repeatedly (Arch. Int. Med., 90:301, 1952; Pharmacol.

PEDIATRICS ◽  
1960 ◽  
Vol 25 (5) ◽  
pp. 742-747
Author(s):  
Robert J. Haggerty ◽  
Mohsen Ziai

A controlled study of the treatment of bacterial meningitis with single and multiple, potentially antagonistic antimicrobial drugs was undertaken. Sixty-five patients received a single and 71 received several drugs in combination. The two groups were generally comparable. There was no significant difference in the results: that is antagonism could not be demonstrated in this clinical study. It seems reasonable to recommend that, in patients over 1 month of age with acute primary bacterial meningitis in whom an etiologic agent cannot be promptly identified, the use of multiple drugs aimed at the three most likely organisms (pneumococcus, meningococcus, H. influenzae) can be employed without danger of clinically apparent antagonism.


2013 ◽  
Vol 7 (05) ◽  
pp. 424-431 ◽  
Author(s):  
Nazif Elaldi ◽  
Mustafa Gokhan Gozel ◽  
Fetiye Kolayli ◽  
Aynur Engin ◽  
Cem Celik ◽  
...  

In this report, a case of community-acquired acute bacterial meningitis (CA-ABM) caused by CTX-M-15-producing Escherichia coli in an elderly male patient was presented in the light of literature. Cultures of cerebrospinal fluid, blood, ear discharge, and stool samples yielded CTX-M-15-producing E. coli in-vitro, which was resistant to the extended-spectrum cephalosporins and ciprofloxacin and susceptible to imipenem, meropenem and amikacin. Meningitis was treated with parenteral meropenem plus parenteral and intraventricular amikacin administration. Since bacterial meningitis is a life-threatening infection, empiric antibiotic therapy with carbapenem can be started before the culture results are obtained, mainly in areas where the ESBL epidemiology is well known.


1979 ◽  
Vol 7 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Hugo Trujillo ◽  
Heli Salgado ◽  
Alvaro Uribe ◽  
Nancy Agudelo ◽  
Carmen Tulia Zapata ◽  
...  

Penetration of the aminoglycoside, amikacin, into the cerebrospinal fluid (CSF) of twenty children with acute bacterial meningitis was studied at various times after intramuscular administration and at various stages of therapy. Six of the patients were evaluated during therapy with amikacin at 7–5 mg/kg (intramuscularly) every 12 hours plus ampicillin every 6 hours at 300 mglkg/day (intravenously); thirteen of the remaining fourteen patients were treated with ampicillin alone, but were given a single intramuscular dose of 7–5 mg/kg of amikacin for evaluation of CSF concentration. Amikacin concentration in CSF with respect to time after administration followed essentially the same pattern as in serum. A minimum concentration of 2 μg/ml was found in 76% of the CSF samples obtained between 0.5 and 7 hours after administration. A mean amikacin serum/CSF ratio of 3:1 was demonstrated up to 7 hours after dose in all patients who underwent clinical improvement. Patient response was predictable by a correlation of in vitro MIC values with in vivo CSF concentration in three of the six patients who received amikacin therapy.


2015 ◽  
Vol 06 (04) ◽  
pp. 549-557 ◽  
Author(s):  
Bankole Peter Kuti ◽  
Emmanuel Olasehinde Bello ◽  
Tolulope Opeoluwa Jegede ◽  
Omolayo Olubosede

ABSTRACT Background: Childhood bacterial meningitis is a neurologic emergency that continues to kill and maims children particularly in developing countries with poor immunization coverage. Objective: This study set out to assess the hospital incidence, pattern of presentation, etiologic agents, outcome and determinants of mortality among the children admitted with bacterial meningitis at the Wesley Guild Hospital (WGH), Ilesa. Patients and Methods: We carried out a retrospective review of admitted cases of bacterial meningitis in children aged one month to 15 years at the WGH, Ilesa over a three year period by looking at the hospital records. Factors in the history and examinations were compared among survivors and those that died to determine factors significantly associated with mortality in these children. Results: Eighty-one (5.5%) of the 1470 childhood admissions during the study period had bacterial meningitis. Male preponderance was observed and two-thirds of the children were infants. More cases were admitted during the wet rainy season than during the dry harmattan season. Haemophilus influenzae type B and Streptococcus pneumoniae were the leading etiologic agents and ciprofloxacin and ceftriaxone adequately cover for these organisms. Twenty-two (27.2%) of the 81 children died, while 34 (42.0%) survived with neurologic deficits. Children with multiple seizures, coma, neck retraction, hyponatremia, hypoglycorrhachia, turbid CSF as well as Gram positive meningitis at presentation were found to more likely to die (P < 0.05). None of these factors however independently predict mortality. Conclusion: Childhood bacterial meningitis often results in death and neurologic deficit among infants and young children admitted at the WGH, Ilesa. Children diagnosed with meningitis who in addition had multiple seizures, neck retraction and coma at presentation are at increased risk of dying.


Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1419
Author(s):  
Dong Zhang ◽  
Shu Xu ◽  
Yiting Wang ◽  
Guoqiang Zhu

Bacterial meningitis (BM) is an acute infectious central nervous system (CNS) disease worldwide, occurring with 50% of the survivors left with a long-term serious sequela. Acute bacterial meningitis is more prevalent in resource-poor than resource-rich areas. The pathogenesis of BM involves complex mechanisms that are related to bacterial survival and multiplication in the bloodstream, increased permeability of blood–brain barrier (BBB), oxidative stress, and excessive inflammatory response in CNS. Considering drug-resistant bacteria increases the difficulty of meningitis treatment and the vaccine also has been limited to several serotypes, and the morbidity rate of BM still is very high. With recent development in neurology, there is promising progress for drug supplements of effectively preventing and treating BM. Several in vivo and in vitro studies have elaborated on understanding the significant mechanism of melatonin on BM. Melatonin is mainly secreted in the pineal gland and can cross the BBB. Melatonin and its metabolite have been reported as effective antioxidants and anti-inflammation, which are potentially useful as prevention and treatment therapy of BM. In bacterial meningitis, melatonin can play multiple protection effects in BM through various mechanisms, including immune response, antibacterial ability, the protection of BBB integrity, free radical scavenging, anti-inflammation, signaling pathways, and gut microbiome. This manuscript summarizes the major neuroprotective mechanisms of melatonin and explores the potential prevention and treatment approaches aimed at reducing morbidity and alleviating nerve injury of BM.


2019 ◽  
Vol 19 (11) ◽  
pp. 914-926 ◽  
Author(s):  
Maiara Bernardes Marques ◽  
Michael González-Durruthy ◽  
Bruna Félix da Silva Nornberg ◽  
Bruno Rodrigues Oliveira ◽  
Daniela Volcan Almeida ◽  
...  

Background:PIM-1 is a kinase which has been related to the oncogenic processes like cell survival, proliferation, and multidrug resistance (MDR). This kinase is known for its ability to phosphorylate the main extrusion pump (ABCB1) related to the MDR phenotype.Objective:In the present work, we tested a new mechanistic insight on the AZD1208 (PIM-1 specific inhibitor) under interaction with chemotherapy agents such as Daunorubicin (DNR) and Vincristine (VCR).Materials and Methods:In order to verify a potential cytotoxic effect based on pharmacological synergism, two MDR cell lines were used: Lucena (resistant to VCR) and FEPS (resistant to DNR), both derived from the K562 non-MDR cell line, by MTT analyses. The activity of Pgp was ascertained by measuring accumulation and the directional flux of Rh123. Furthermore, we performed a molecular docking simulation to delve into the molecular mechanism of PIM-1 alone, and combined with chemotherapeutic agents (VCR and DNR).Results:Our in vitro results have shown that AZD1208 alone decreases cell viability of MDR cells. However, co-exposure of AZD1208 and DNR or VCR reverses this effect. When we analyzed the ABCB1 activity AZD1208 alone was not able to affect the pump extrusion. Differently, co-exposure of AZD1208 and DNR or VCR impaired ABCB1 activity, which could be explained by compensatory expression of abcb1 or other extrusion pumps not analyzed here. Docking analysis showed that AZD1208 is capable of performing hydrophobic interactions with PIM-1 ATP- binding-site residues with stronger interaction-based negative free energy (FEB, kcal/mol) than the ATP itself, mimicking an ATP-competitive inhibitory pattern of interaction. On the same way, VCR and DNR may theoretically interact at the same biophysical environment of AZD1208 and also compete with ATP by the PIM-1 active site. These evidences suggest that AZD1208 may induce pharmacodynamic interaction with VCR and DNR, weakening its cytotoxic potential in the ATP-binding site from PIM-1 observed in the in vitro experiments.Conclusion:Finally, the current results could have a pre-clinical relevance potential in the rational polypharmacology strategies to prevent multiple-drugs resistance in human leukemia cancer therapy.


Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 705
Author(s):  
Asmaa M. El-Kady ◽  
Iman A. M. Abdel-Rahman ◽  
Samer S. Fouad ◽  
Khaled S. Allemailem ◽  
Taghrid Istivan ◽  
...  

Giardiasis is a major diarrheal disease affecting approximately 2.5 million children annually in developing countries. Several studies have reported the resistance of Giardia lamblia (G. lamblia) to multiple drugs. Therefore, identifying an effective drug for giardiasis is a necessity. This study examined the antiparasitic effect of Punica granatum (pomegranate) and evaluated its therapeutic efficacy in rats infected with G. lamblia. In vitro study showed high efficacy of pomegranate peel ethanolic extract in killing G. lamblia cysts as demonstrated by eosin vital staining. We showed that treating infected rats with pomegranate extract resulted in a marked reduction in the mean number of G. lamblia cysts and trophozoites in feces and intestine respectively. Interestingly, the number of G. lamblia trophozoites and cysts were significantly lower in the pomegranate extract-treated group compared to the metronidazole-positive control group. Moreover, pomegranate extract treatment significantly induced nitric oxide (NO) and reduced serum IL-6 and TNF-α, compared to infected untreated rats. Histological and scanning electron microscopy (SEM) examination of the jejunum and duodenum of pomegranate extract-treated animals confirmed the antiparasitic effect of the extract, and demonstrated the restoration of villi structure with reduction of villi atrophy, decreased infiltration of lymphocytes, and protection of intestinal cells from apoptotic cell death. In conclusion, our data show that the pomegranate peel extract is effective in controlling G. lamblia infections, which suggests that it could be a viable treatment option for giardiasis.


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