&shy;&shy;&shy;&shy;&shy;Cefotaxime: A reappraisal for use in lower respiratory tract infections

Nikhilesh Jain

doi:10.12688/f1000research.74850.1

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Review

Cefotaxime: A reappraisal for use in lower respiratory tract infections

[version 1; peer review: 1 not approved]

Nikhilesh Jain

PUBLISHED 23 Mar 2022

Author details Author details

Critical Care Services, CHL Hospital, Indore, Madhya Pradesh, India

Nikhilesh Jain
Roles: Project Administration, Supervision, Validation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

Lower respiratory tract infections (LRTIs) are documented to cause significant morbidity and mortality in patients worldwide. During the ongoing pandemic, LRTIs like pneumonia are posing a major health concern for patients and the healthcare system. In COVID-19-related pneumonia bacterial co-infection is not uncommon and remains a leading cause of mortality in affected cases. Cefotaxime, a third-generation parenteral cephalosporin, has a broader spectrum of antimicrobial activity with a high-level of stability against β-lactamases. Despite many years of clinical usage for cefotaxime in LRTIs, resistance to this drug does not seem to be a major concern, and it is still one of the cornerstones in the choice effective antimicrobial therapy. This paper attempts to delineate available evidence for cefotaxime usage in various clinical situations like community acquired pneumonia (CAP), nosocomial pneumonia, acute exacerbations of chronic bronchitis (AECB) and acute bronchitis. This may be of help for a clinician to develop a thorough viewpoint on the rational use of this time-tested antimicrobial agent and to take an apt clinical decision towards the optimum patient care.

Keywords

Cefotaxime, LRTI, Community acquired pneumonia

Corresponding author: Nikhilesh Jain

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2022 Jain N. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Jain N. Cefotaxime: A reappraisal for use in lower respiratory tract infections [version 1; peer review: 1 not approved]. F1000Research 2022, 11:350 (https://doi.org/10.12688/f1000research.74850.1) First published: 23 Mar 2022, 11:350 (https://doi.org/10.12688/f1000research.74850.1) Latest published: 30 Jan 2023, 11:350 (https://doi.org/10.12688/f1000research.74850.2)

Introduction

In late 2019, a pneumonia of unknown cause was diagnosed in a few patients in Wuhan, China and on 7 January 2020; the organism responsible for this pneumonia was identified as a new coronavirus which was named as the 2019 novel coronavirus (2019-nCoV).¹ Subsequently, the coronavirus disease 2019 (COVID-19), and subsequent lower respiratory tract infection (LRTI) like pneumonia have remained troublesome buzzwords for all components of a healthcare system.

Lower respiratory tract infections (LRTIs) are considered to be comprised of acute bronchitis, bronchiolitis, influenza. They are a substantial cause of morbidity and death in patients globally.² The Global Burden of Disease Study assessed evidence for the global, regional and national morbidity and mortality of LRTIs which revealed that, during 2016, LRTIs remained a significant contributor to infectious disease-related mortality and the fourth most common cause of death on the whole.³

The surge in infections acquired from the community and hospital caused by multidrug-resistant (MDR) bacterial pathogens is constraining choices for effective antibiotic therapy. To add to the worrying spread of antimicrobial resistance, newer antimicrobial agents are not being developed to balance it.⁴ Resistance to even novel antimicrobials has been documented.⁴ In the aforementioned scenario, judicious and rational use of conventional antimicrobial agents may serve as a possible option for the treatment of MDR bacterial pathogens. It can give therapeutic optimization choices to widen the spectrum of antibiotics, with the aim to preserve newer antimicrobial agents and counter drug resistance.⁴

Cefotaxime, one of the most clinically utilized cephalosporins, has been in clinical usage for a long time and is still deemed to be effective if used appropriately.

Following on this background, the present narrative review aims to revisit the basic science behind cefotaxime and its clinical applicability in one of the most common bacterial infections, lower respiratory tract infection (LRTI). This reappraisal can be of use to clinicians for developing a scientific rationale and subsequent clinical decision for utilizing the right drug for the right patient.

LRTI

In this world of competing health priorities, respiratory tract infections have always posed a huge burden in terms of morbidity and mortality. Based on the site of infection, they are broadly classified into upper and lower respiratory infections.⁵ LRTI is an umbrella term including different diseases like acute bronchitis, pneumonia, acute exacerbation of chronic lung diseases such as chronic obstructive pulmonary disease (COPD) or bronchiectasis. The European Respiratory Society defines various terms related to LRTIs, as described in Table 1.⁶

Table 1. Common terms related to LRTI.

Respiratory infection type	Criteria
Lower respiratory tract infection (LRTI)	Acute illness presenting with less than 21 days duration. usually with cough as the main symptom, with ≥ 1 additional respiratory tract symptom like sputum production, dyspnoea, wheeze or chest discomfort/pain) without any alternative explanation like sinusitis or asthma.
Acute bronchitis (AB)	An acute illness, in a patient without chronic lung disease, with symptoms including cough (± productive) and clinical features of LRTI without any alternative explanation like sinusitis or asthma.
Influenza	Acute illness usually presenting with fever with ≥ 1 symptom like headache, myalgia, cough and sore throat.
Suspected community-acquired pneumonia (CAP)	An acute illness with cough and ≥ new focal chest signs, fever lasting >4 days or dyspnoea/tachypnoea, and without any other obvious cause.
Definite community-acquired pneumonia (CAP)	Criteria of suspected CAP with chest radiograph findings of lung shadowing which is likely to be new.
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD)	Worsening of COPD patient's baseline dyspnoea, cough and/or sputum beyond routine variability demanding a change in management.
Acute exacerbation of bronchiectasis (AEBX)	In a bronchiectasis patient, deterioration in the patient's baseline dyspnoea and/or cough and/or sputum beyond routine variability demanding a change in management.

Disease burden in various age groups

LRTI has been reported to be the fourth most common cause of death across the globe. According to the Global Burden of Disease study, in 2016, LRTIs led to 23,77,697 deaths worldwide. Among them, 6,52,572 deaths were documented in children less than five years of age. The study also reported 10,80,958 deaths in adults older than 70 years.³ LRTIs are one of the leading cause of mortality in children under five years of age and account for approximately four million deaths per year.⁷ These account for 13.1% of all deaths in the under-five age group. However, these infections are not limited to childhood and predispose the individual to chronic respiratory diseases later in life.⁷

As per the GBD-2016 study, the maximum number of LRTI episodes among children younger than five years across the globe were reported in south Asia (18.76 million).³

Pneumonia has been reported to be the single largest cause of mortality among children worldwide.⁸ Pneumonia is reported to have an incidence of 24.8 per 10,000 adults in a year. Extremes of age (less than five years and elderly population more than 65 years) are predominant contributors to the quantum of pneumonia cases overall.⁹

Microbial spectrum

Pneumococcal pneumonia remains a leading cause of LRTI incidence and mortality in both children and adults. The infection episodes caused by Streptococcus pneumoniae outnumber the cumulative number of infections caused by all other pathogens. The incidence of LRTI attributable to S. pneumoniae across all ages was 26.7 per 1,000 people between 1995 and 2016.³ This incidence is disproportionately higher in children <5 years (70.7/1000 people) and elderly people >70 years of age (72.8/1000 people).³ There is suggestive evidence that S. pneumoniae may occur as a coinfection with viral infections or may follow a viral infection.¹⁰

Apart from S. pneumoniae, other Gram-positive bacteria responsible for LRTI include Staphylococcus aureus, as well as Gram-negative organisms such as Pseudomonas aeruginosa, Haemophilus influenzae, Klebsiella pneumoniae, and Escherichia coli.¹¹

Common viral pathogens implicated in LRTI include human rhinovirus, influenza viruses and human coronavirus, human parainfluenza viruses, human respiratory syncytial virus and human metapneumovirus (Table 2).¹²

Table 2. Lower respiratory tract infectioms: common causative microorganisms.

Gram positive bacteria	Gram negative bacteria	Virus
Streptococcus pneumoniae	Pseudomonas aeruginosa	Human rhinovirus
Staphylococcus aureus	H. Influnzae	Influenza virus
	Klebsiella pneumonia	Human parainfluenza virus
	E. coli	Human coronavirus
	Moraxella catarrhalis¹³	Human respiratory syncytial virus
	Legionella spp.¹⁴
	Chlamydia pneumoniae¹⁴
		Human metapneumovirus

Risk factors for LRTI

Apart from age extremes, other risk factors which predispose to LRTIs include poor sanitization owing to crowded living conditions, severe malnutrition, lack of breast feeding for infants, HIV infection, lack of immunization, chronic illness, family history of LRTIs and exposure to tobacco smoke and air pollutants.¹⁵^,¹⁶

LRTIs are a major issue in critically ill patients, being associated with prolonged hospitalization, higher costs, and possibly, an increase in mortality.¹⁷

Cefotaxime: molecular profile

Cephalosporins have a broad spectrum of antimicrobial activity, good clinical efficacy, favorable pharmacokinetics and tolerability profile in clinical use, making them frequently utilized antimicrobial agents.¹⁸ Like penicillin, they belong to the β-lactam class of drugs.¹⁹

On the basis of chronological order of drug discovery and antimicrobial properties, these antibiotic agents have been grouped into various generations, from first to fifth,²⁰ as shown in Table 3.

Table 3. Classification of Cephalosporins.²¹

1^st Generation	2^nd Generation	3^rd Generation	4^th Generation	5^th Generation
cefazolin	cefamandole	cefotaxime	cefipime	ceftaroline
cephalothin	cefuroxime	ceftriaxone		ceftobiprole
cephapirin	cefoxitin	ceftizoxime
cephalexin	cefotetan	ceftazidime
cefadroxil	cefmetazole	cefoperazone
cephradine	cefaclor	cefixime
	cefpodoxime

Third-generation cephalosporins are usually efficacious against Gram-negative as well as Gram-positive organisms.²⁰ Normally, as we move from first to third, the microbicidal activity of cephalosporins decreases against Gram-positive organisms but increases against Gram-negative bacilli.¹⁸ Furthermore, the resistance against β -lactamases increases from first to fifth generations.¹⁸

Cefotaxime is a β-lactam antibiotic, first produced in 1976, belonging to third-generation cephalosporins and is therapeutically approved for the treatment of various Gram-positive, Gram-negative, and anaerobic bacteria.²² It has been widely available for decades and still holds a vital place in the management of various serious infections.²³

Molecular structure

Cefotaxime sodium is the generally available formulation of cefotaxime which is semisynthetic in nature.²⁴ It comprises an acetyl side chain of an aminothiazoyl ring, along with an a-syn-methoxyimino group.

Intrinsic activity and spectrum of action

Cefotaxime is active in vitro against a broad range of Gram-positive, Gram-negative and anaerobic organisms (Table 4). It retains a high level of stability in the presence of both the β-lactamases including penicillinases and cephalosporinases produced by Gram-negative as well as Gram-positive bacteria.²⁴

Table 4. Organisms sensitive to cefotaxime.²⁵

Gram positive organisms

Gram negative organisms

Anaerobic organisms

✓ Enterococcus spp.
✓ Staphylococcus aureus
✓ Staphylococcus epidermidis
✓ Streptococcus pneumoniae
✓ Streptococcus pyogenes
✓ Streptococcus viridans spp.

✓ Acinetobacter spp.
✓ Citrobacter spp.
✓ Enterobacter spp.
✓ Escherichia coli
✓ Haemophilus influenzae
✓ Haemophilus parainfluenzae
✓ Klebsiella spp.
✓ Morganella morganii
✓ Neisseria gonorrhoeae
✓ Neisseria meningitidis
✓ Proteus mirabilis
✓ Proteus vulgaris
✓ Providencia rettgeri
✓ Providencia stuartii
✓ Serratia marcescens

✓ Bacteroides spp.
✓ Clostridium spp.
✓ Fusobacterium spp.
✓ Peptococcus spp.
✓ Peptostreptococcus spp.

Clinical pharmacology

Like other cephalosporins, cefotaxime inhibits bacterial cell wall synthesis in a way equivalent to penicillin. Its β-lactam rings bind to penicillin-binding proteins (PBPs) and inhibits transpeptidation in peptidoglycan cell wall synthesis of susceptible bacteria. This leads to autolysis of the bacteria.²⁵ Inhibition experiments have demonstrated high affinity of cefotaxime for PBPs Ib and III, which results in a high bactericidal activity.

The resistance developed by various bacteria against β-lactam antibiotics is mainly due to their β-lactamase-producing capability. Similar to other β-lactam group of antibiotics, β-lactamases can cause hydrolysis of cefotaxime, which reduces its bactericidal efficacy despite the molecule being stable against the activity of most β-lactamases.²⁵

Once administered, it is metabolized in the liver²⁶ where cefotaxime converts its primary metabolite, desacetyl cefotaxime (des-CTX), followed by desacetyl cefotaxime lactone and subsequently to M metabolites.²⁶ Most of the cefotaxime (>80%) and its metabolites are excreted through the renal route. The antimicrobial activity of des-CTX has been reported to be eight-fold lower than cefotaxime.²⁷ Usually, cefotaxime and des-CTX act synergistically with antagonism documented in strains of Morganella and Proteus vulgaris, and presence of des-CTX has been shown to enhance the efficacy of cefotaxime.²⁸

Administration and dose

Cefotaxime formulations are available as powder (500 mg, 1 g, 2 g, and 10 g vials) or premixed solutions (1gm and 2gm) to be administered through intramuscular and intravenous routes. The powder form is available in 500 mg, 1 g, 2 g, and 10 g vials while the premixed solution is available as 1gm and 2gm for injection.²⁵ Cefotaxime is used as as therapeutic agent of lower respiratory infections, meningitis, urinary tract infections, pelvic inflammatory disease, skin and skin structure infections, and gonorrhea (Table 5).²⁹

Table 5. General dosing guidelines for cefotaxime.²⁴

Type of infection	Daily dose (Grams)	Frequency
Uncomplicated infections	2	1 gram every 12 hours
Moderate to severe infections	3	1-2 grams every 8 hours
Infections commonly needing antibiotics in higher dosage (e.g., septicemia)	6-8	2 grams every 6-8 hours
Life-threatening infections	Up to 12	2 grams every 4 hours

Key advantages

Cefotaxime has a broader spectrum of activity against Gram-positive, Gram-negative aerobic and anaerobic bacteria, and has a better efficacy against Gram-negative bacteria compared to previous generations of cephalosporins.³⁰

It is generally well-tolerated and hypersensitivity reactions such as rash, fever, and pruritus are relatively infrequent. Cefotaxime has not been reported to cause hypoprothrombinemia or disulfiram-like reactions, as has been noted with other cephalosporins. One more favorable characteristic of cefotaxime is that its usage is not found to be associated with significant occurrence of coagulopathies and pseudocholelithiasis.²⁵

Cefotaxime therapy is simple, generally economical and has a relatively broad spectrum of activity compared to many other antimicrobial agents used for postoperative nosocomial pneumonia.³¹

Cefotaxime: clinical evidence in LRTI

Community acquired pneumonia (CAP)

Quite a good amount of published evidence prevails when the use of cefotaxime in CAP is considered. Cefotaxime in combination with Gentamycin has been recommended as one of the first line agent in management of severely ill hospitalized patients with community acquired pneumonia by Norwegian guidelines.³² In a retrospective observational study conducted by the University Hospital of North Norway, Cefotaxime was one of the most commonly prescribed antibiotics, in combination with other antimicrobials, among hospitalized CAP patients.³³

Another study documents the successful use of cefotaxime among pediatric patients with necrotizing pneumonia (NN). NN is a complication of pneumonia with very limited data in pediatric patients. Retrospective-prospective data of 51 NN patients admitted to pediatric intensive care units between 2010 and 2018 were reported. Out of 34 patients with a definite etiologic diagnosis, 29 patients were infected with pneumococci. Other microbes involved were Streptococcus pyogenes, Streptococcus anginosus and Haemophilus influenza. Cefotaxime was used in 49 patients (in combination with clindamycin in 44 patients). Antibiotics with pleural effusion was sufficient in 48 patients. Only three patients required a surgical intervention. All patients recovered and were discharged successfully.³⁴

A study conducted by the Infectious Disease Surveillance of Pediatrics (ISPED) collaboration group in China found that H. Influenzae, which is one of the common pathogens behind CAP in children, has developed phenomenal resistance against antibiotics.³⁵ More than two thirds of H. influenzae strains have been reported to be ampicillin-resistant and almost one third of strains were resistant to common antibiotics like azithromycin and cefuroxime. Cefotaxime retained activity against 94% of strains.³⁵ Based on above, Cefotaxime was proposed as a first-choice therapy for treating ampicillin-resistant H. influenzae strains.³⁵ Similar results were documented by another study from China in which 90% H. influenzae samples from children suffering with CAP were Cefotaxime-sensitive.³⁶ The same samples reported 100% resistance to ampicillin and more than 60% resistance to trimethoprim, cefaclor and cefuroxime.³⁶ Another study conducted in rural Vietnam, which studied the antimicrobial susceptibility of S. pneumoniae in children under five years reported high resistance to oral antibiotics like co-trimoxazole (78%), tetracycline (75%), phenoxymethylpenicillin (75%), erythromycin (70%) and ciprofloxacin (28%) along with minimal resistance to cefotaxime (2%), benzylpenicillin (4%) and amoxycillin (4%).³⁷

A meta-analysis was conducted in Africa to evaluate the susceptibility of CAP-causing S. pneumoniae, among patients having invasive pneumonia from 1978 to 2011.³⁸ Results revealed that S. pneumoniae isolated from the nasopharynx/oropharynx were often resistant to ampicillin (26.4%), penicillin (25.4%), sulfamethoxazole (47.5%) and tetracycline (33.9%). On the contrary, 98.3% samples were sensitive to ceftriaxone/cefotaxime.³⁸

Another paper evaluated the resistance pattern of S. pneumoniae strains among organ transplant patients. Susceptibility to azithromycin, erythromycin, clarithromycin, levofloxacin and a trimethoprim-sulfamethoxazole combination was seen in 53%, 67%, 71%, 75% and 53% strains respectively, with no resistance detected against cefotaxime, vancomycin and intravenous penicillin in the above cohorts.³⁹

One study conducted in Yuying Children’s Hospital, Wenzhou, China specifically looked at antimicrobial resistance patterns in children under 12 years suffering from invasive pneumococcal disease. Penicillin-intermediate S. pneumoniae (PISP) and penicillin-resistant S. pneumoniae (PRSP) incidences were noted to be 30% and 41%, respectively. Reported resistance against erythromycin (94%) and lincomycin (88%) was high and the lowest resistance rate was seen for cefotaxime (22%).⁴⁰ A similar study conducted in Spain reported less resistance against cefotaxime as compared to other antibiotics viz. penicillin, erythromycin and tetracycline, in S. pneumoniae strains responsible for causing CAP, meningitis in adults and acute otitis media in children.⁴¹

A study conducted in the department of Microbiology, Vardhman Mahaveer Medical College, in Safdarjung Hospital, India, compared BacT/Alert 3D with conventional culture for diagnosing CAP. This study also reported antimicrobial susceptibility using the disk diffusion technique.⁴² The studied microbes included S. pneumoniae, S. aureus, K. pneumoniae, H. influenzae, Streptococcus Group A and G. Out of a total of 34 isolates of the above-mentioned microbes, all except two isolates of K. pneumoniae were sensitive to cefotaxime.⁴²

As per the SENTRY study conducted in Latin America during 1997-2001 on pneumococcal isolates from mainly community-acquired respiratory tract infections, resistance rates were very low (0.4%) for cefotaxime vis-à-vis other antibiotics, including penicillin (11.9%), azithromycin (88.5%), clarithromycin (87.5%), tetracycline (79.5%) and trimethoprim + sulphamethoxazole (60.5%).⁴³

CAP during Coronavirus Disease 2019 (COVID-19) pandemic

Currently, viruses have become the predominant causative etiology for respiratory infections; owing to the availability of effective vaccination with pneumococcal conjugate vaccines, bacterial etiologies remain the leading cause of mortality among CAP patients.⁴⁴ Among patients with COVID-19-related pneumonia, co-infection with bacteria is also a major concern. Common bacteria implicated in these infections include S. pneumoniae, H. influenzae, Chlamydia pneumoniae, and S aureus. Empirical treatment with antibacterial agents can be useful to reduce mortality in such cases.⁴⁴ The latest CAP guidelines released by the American Thoracic Society and the Infectious Diseases Society of America recommend cefotaxime in combination with macrolides or doxycycline as one of the empiric antibiotics for management of such infections.⁴⁵

Nosocomial or hospital-acquired pneumonia

Several noncomparative and comparative studies have assessed the efficacy of cefotaxime as treatment for nosocomial or hospital-acquired pneumonia. Nosocomial pneumonia is associated with significant increase in duration of hospital stay, greater expenses as well as a higher incidence of morbidity and mortality.⁴⁶

In an Indian study by M. Merchant et al., incidence of nosocomial infection was documented at 1.8% in patients of general wards, against 16.7% in ICU patients. It reported cefotaxime (34%) as a commonly utilized antibiotic, followed by amikacin and gentamicin.⁴⁷

A German study group by HP Bruch⁴⁸ evaluated twice a day dosing of cefotaxime in patients with postoperative pneumonia. A total of 515 postoperative pneumonia patients were given 1 or 2 g cefotaxime twice a day. Patients without serious underlying diseases (n=88), receiving 1 g every 12 hours dosage regimen in this study, got clinically cured along with eradication of all pathogens.⁴⁸ In the cohort with severe infection/severe underlying disease who were given 2 g every 12 hours cefotaxime, the overall clinical success rate (cumulated cured and improved) was 98.4%. The above-mentioned findings support the use of cefotaxime as a feasible option instead of empiric monotherapy to manage nosocomial pneumonia, in surgical-service patients on long-term artificial ventilation who do not have neutropenia.⁴⁸ A similar study which evaluated a twice-a-day dosing of cefotaxime (2 g every 12 hours) in patients with severe nosocomial pneumonia documented this regimen of cefotaxime as adequate and appropriate. Authors of the above study also suggested a combination of cefotaxime with aminoglycosides to be reserved for cases with suspected multi-resistant Gram-negative bacterial infections.⁴⁹

An open, controlled, randomized and multicentric study which evaluated the use of cefotaxime and ceftriaxone in adult patients with nosocomial pneumonia, showed 80% clinical and 93% bacteriologic success rate with cefotaxime, comparable to ceftriaxone.⁴⁶ In terms of adverse events, a higher incidence of gall bladder sludge and diarrhea was reported for the ceftriaxone group.

One Canadian multicentric, open labeled, randomized trial compared the effects of cefotaxime and ceftriaxone in 57 patients with nosocomial LRTI. In this study, 28 out of 30 patients in the cefotaxime group showed cure/improvement after seven to 10 days of therapy, which was relatively similar to the ceftriaxone group (25 out of 27). G.E. Garber et al., the investigators of the aforementioned study, inferred that cefotaxime at 1 g intravenous (I.V.) every eight hours was non-inferior to ceftriaxone at 1 g I.V. every 12 hours, with a trend for less likely side effects, reinfections, and superinfections.⁵⁰

A multicentric study was conducted in 32 hospitals on 588 nosocomial pneumonia patients not on mechanical ventilation. The patients were randomized to receive either cefotaxime or routinely used antibiotic combination. The cure rate was significantly more in the cefotaxime arm (79%) compared to the comparator arm (71%). Moreover, the seriously adverse events were significantly more common in the comparator arm as compared to the cefotaxime arm.⁵¹ These results hint at superiority of cefotaxime as an empirical therapy for nosocomial pneumonia.⁵¹

A study was conducted on 46 adults hospitalized with pneumococcal pneumonia in Spain. The common underlying diseases in these patients included heart disease, COPD/asthma and diabetes mellitus. When the resistance pattern to antibiotics of the pneumococci were studied, it was reported to be 15%, 11% and 6% with penicillin, erythromycin and cefotaxime respectively.⁵²

Acute exacerbations of chronic bronchitis (AECB)

A double-blind prospective study from The Netherlands evaluated a total of 180 hospitalized patients with acute purulent exacerbations of chronic bronchitis. The patients received 1 g intramuscular injection of either cefodizime or cefotaxime two times a day for seven days. In this study, F. P. V. Maesen et al. found statistically non-significant difference between both study molecules in terms of overall efficacy and bacterial eradication. Authors pointed out an interesting fact in the discussion that in spite of wide and long-term usage of cefotaxime in this hospital set up, there was no fear of widespread increase in resistance.⁵³

The same study group evaluated cefotaxime use in hospital in-patients with acute purulent exacerbations of chronic bronchitis. In this study, 30 patients were given 1 g cefotaxime intramuscularly two times a day for a longer duration (10 days).⁵³ Additionally, 10 patients who received a higher dose of cefotaxime (2 g twice daily) were also included in this particular study. The clinical results were excellent in 21 patients out of 30 patients who received 1 g daily, and all patients given twice 2 g reported excellent cure rates.⁵³

Another randomized, controlled, prospective nonblinded study was performed for 93 hospitalized patients requiring antibiotics for acute exacerbations of chronic obstructive pulmonary disease. This study compared continuous versus intermittent administration of cefotaxime, where forty-seven patients received 2 g of cefotaxime intravenously over 24 hours plus a loading dose of 1 g, and 46 patients were given the drug intermittently (1 g three times daily). The study concluded that continuous administration of cefotaxime at a lower dose was equally effective pharmacodynamically and microbiologically, maybe more cost-effective, and offered at least a similar clinical efficacy.⁵⁴

Acute bronchitis

Acute bronchitis is characterized by extensive airway inflammation and presents with cough (productive/non-productive) in absence of any chronic lung illness. For the majority, the etiology includes viruses like influenza A and B, parainfluenza and respiratory syncytial virus.⁵⁵ Bacterial infections may also cause bronchitis in people with underlying health issues/prior co-morbidities. Bacterial infections associated with bronchitis include Mycoplasma pneumoniae, H. influenzae, Moraxella catarrhalis and Bordetella pertussis.⁵⁶ Though the role of antibiotics in management of acute bronchitis remains controversial,⁵⁶ there is some evidence supporting use of cefotaxime to treat this disease.

M Rylski et al. conducted a study on 100 patients with respiratory infections like bronchopneumonia, acute bronchitis and chronic bronchitis who underwent fiberoptic bronchoscopy. A total of 48% of these patients tested positive for bacterial flora (aerobic, anaerobic and mixed bacterial flora). Pneumococci and Bacteroides melaningogenicus were commonly isolated. From antibacterial susceptibility reports, cefotaxime was one of the antibiotics to which high sensitivity was reported.⁵⁷

In another publication, K Konishi et al. reported 129 cases of respiratory tract and other infections which were treated with cefotaxime. Out of 129 cases, the majority presented pneumonia, 20 cases each of bronchopneumonia and acute bronchitis, 14 of chronic bronchitis and 17 AECB. These patients received 0.5 to 8 mg of cefotaxime daily through the intravenous route for two to 61 days. Cefotaxime was documented to be efficacious in 87.1% (108/124) cases. The study concluded that cefotaxime is quite effective against LRTIs.⁵⁸

Conclusions

LRTIs are responsible for substantial morbidity and mortality across the globe. LRTIs caused by various organisms can often be complicated by emerging antimicrobial resistance. Strategies to promote timely and appropriate use of effective antibiotics should be implemented to reduce symptom duration, complications and mortality associated with LRTIs. Cefotaxime, a third-generation injectable antibiotic, has demonstrated good efficacy and safety in the management of LRTIs including CAP, hospital-acquired/nosocomial-acquired pneumonia, acute exacerbation of pneumonia and acute bronchitis caused by both Gram-positive and Gram-negative bacteria. Despite the usage of cefotaxime against LRTIs for several decades, significant resistance has not been reported and the drug remains a reasonable option in managing these infections in present times.

Data availability

No data are associated with this article.

References

1. Wang M, Zhou Y, Zong Z, et al.: A precision medicine approach to managing 2019 novel coronavirus pneumonia. Precis. Clin. Med. 2020 Mar 25; 3(1): 14–21. PubMed Abstract | Publisher Full Text
2. Feldman C, Richards G: Appropriate antibiotic management of bacterial lower respiratory tract infections. F1000Research. 2018 Jul 23; 7: 1121. PubMed Abstract | Publisher Full Text
3. Troeger C, Blacker B, Khalil IA, et al.: Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect. Dis. 2018 Nov 1; 18(11): 1191–1210. PubMed Abstract | Publisher Full Text
4. Cassir N, Rolain J-M, Brouqui P: A new strategy to fight antimicrobial resistance: the revival of old antibiotics. Front. Microbiol. 2014 [cited 2021 Apr 5]; 5. PubMed Abstract | Publisher Full Text
5. Dasaraju PV, Liu C: Infections of the Respiratory System. Baron S, editor. Medical Microbiology. 4th ed.Galveston (TX): University of Texas Medical Branch at Galveston; 1996 [cited 2021 Apr 6]. Reference Source
6. Woodhead M, Blasi F, Ewig S, et al.: Guidelines for the management of adult lower respiratory tract infections - Summary. Clin. Microbiol. Infect. 2011 Nov 1; 17: 1–24. PubMed Abstract | Publisher Full Text
7. WHO|Pneumonia: the forgotten killer of children: WHO. World Health Organization. [cited 2021 Apr 6]. Reference Source
8. Pneumonia: [cited 2021 Apr 6]. Reference Source
9. Mahashur A: Management of lower respiratory tract infection in outpatient settings: Focus on clarithromycin. Lung India Off. Organ Indian Chest Soc. 2018 Apr; 35(2): 143–149. PubMed Abstract | Publisher Full Text
10. Malosh RE, Martin ET, Ortiz JR, et al.: The risk of lower respiratory tract infection following influenza virus infection: A systematic and narrative review. Vaccine. 2018 Jan 2; 36(1): 141–147. PubMed Abstract | Publisher Full Text
11. Khan S, Priti S, Ankit S: Bacteria Etiological Agents Causing Lower Respiratory Tract Infections and Their Resistance Patterns. Iran. Biomed. J. 2015 Oct; 19(4): 240–246. PubMed Abstract
12. Ieven M, Coenen S, Loens K, et al.: Aetiology of lower respiratory tract infection in adults in primary care: a prospective study in 11 European countries. Clin. Microbiol. Infect. 2018 Nov 1; 24(11): 1158–1163. PubMed Abstract | Publisher Full Text
13. Abdullah FE, Ahuja KR, Kumar H: Prevalence and emerging resistance of Moraxella catarrhalis in lower respiratory tract infections in Karachi. JPMA J. Pak. Med. Assoc. 2013 Nov; 63(11): 1342–1344.
14. Thiem U, Heppner H-J, Pientka L: Elderly patients with community-acquired pneumonia: optimal treatment strategies. Drugs Aging. 2011 Jul 1; 28(7): 519–537. Publisher Full Text
15. Forum of International Respiratory Societies, European Respiratory Society: The global impact of respiratory disease.2017.
16. Indian Pediatrics - Editorial: [cited 2021 Apr 6]. Reference Source
17. Zampieri FG, Póvoa P, Salluh JI, et al.: Lower Respiratory Tract Infection and Short-Term Outcome in Patients With Acute Respiratory Distress Syndrome. J. Intensive Care Med. 2018 Apr 26; 35(6): 588–594. Publisher Full Text
18. Klein NC, Cunha BA: The selection and use of cephalosporins: a review. Adv. Ther. 1995 Apr; 12(2): 83–101.
19. Arumugham VB, Cascella M: Third Generation Cephalosporins. StatPearls. Treasure Island (FL): StatPearls Publishing; 2021 [cited 2021 Apr 1]. Reference Source
20. El-Shaboury SR, Saleh GA, Mohamed FA, et al.: Analysis of cephalosporin antibiotics. J. Pharm. Biomed. Anal. 2007 Sep 21; 45(1): 1–19. Publisher Full Text
21. Classification of Cephalosporin Antibiotics. MediMoon. 2013 [cited 2021 Apr 5]. Reference Source
22. Dudley MN, Barriere SL: Cefotaxime: microbiology, pharmacology, and clinical use. Clin. Pharm. 1982 Apr; 1(2): 114–124. PubMed Abstract
23. Plosker GL, Foster RH, Benfield P: Cefotaxime. A pharmacoeconomic review of its use in the treatment of infections. PharmacoEconomics. 1998 Jan; 13(1 Pt 1): 91–106. Publisher Full Text
24. Cefotaxime (Cefotaxime for Injection): Uses, Dosage, Side Effects, Interactions, Warning: RxList. [cited 2021 Apr 4]. Reference Source
25. Padda IS, Nagalli S: Cefotaxime. StatPearls. Treasure Island (FL): StatPearls Publishing; 2021 [cited 2021 Apr 3]. Reference Source
26. Coombes JD: Metabolism of cefotaxime in animals and humans. Rev. Infect. Dis. 1982 Oct; 4 Suppl: S325–S332. PubMed Abstract | Publisher Full Text
27. Chin NX, Neu HC: Cefotaxime and desacetylcefotaxime: an example of advantageous antimicrobial metabolism. Diagn. Microbiol. Infect. Dis. 1984 Jun; 2(3 Suppl): 21S–31S. PubMed Abstract
28. Antibacterial Activity of Desacetylcefotaxime alone and in combination with Cefotaxime by Harold C. Neu Reviews of Infectious diseases. September-October 1982; 4(Supplement _2): S374–S378. Publisher Full Text
29. Castle SS: Cefotaxime. Enna SJ, Bylund DB, editors. xPharm: The Comprehensive Pharmacology Reference. New York: Elsevier; 2007 [cited 2021 Apr 11]; p. 1–4. Reference Source
30. Carmine AA, Brogden RN, Heel RC, et al.: Cefotaxime. A review of its antibacterial activity, pharmacological properties and therapeutic use. Drugs. 1983 Mar; 25(3): 223–289. PubMed Abstract | Publisher Full Text
31. Wittmann DH, Jones RN, Malledant J, et al.: Cefotaxime in the treatment of prophylaxis of surgical infections. J. Chemother. Florence Italy. 1997 May; 9 Suppl 2: 19–33.
32. Pneumoni, samfunnservervet: Helsedirektoratet.[cited 2021 Apr 8]. Reference Source
33. Høgli JU, Garcia BH, Svendsen K, et al.: Empirical prescribing of penicillin G/V reduces risk of readmission of hospitalized patients with community-acquired pneumonia in Norway: a retrospective observational study. BMC Pulm. Med. 2020 Jun 15 [cited 2021 Apr 8]; 20: 169. PubMed Abstract | Publisher Full Text Reference Source
34. Blanco-Iglesias E, Oñoro G, Almodovar-Martín JL, et al.: Retrospective Study in Children With Necrotizing Pneumonia: Nine Years of Intensive Care Experience. Pediatr. Infect. Dis. J. 2020 Jul; 39(7): 571–575. Publisher Full Text
35. Antibiotic Resistance Profiles of Haemophilus influenzae Isolates from Children in 2016: A Multicenter Study in China - PubMed.[cited 2021 Apr 10]. Reference Source
36. Lu Y-Y, Luo R, Fu Z: Pathogen distribution and bacterial resistance in children with severe community-acquired pneumonia. Zhongguo Dang Dai Er Ke Za Zhi Chin J Contemp Pediatr. 2017 Sep; 19(9): 983–988.
37. Hoa NQ, Trung NV, Larsson M, et al.: Decreased Streptococcus pneumoniae susceptibility to oral antibiotics among children in rural Vietnam: a community study. BMC Infect. Dis. 2010 Mar 31; 10: 85. PubMed Abstract | Publisher Full Text
38. Ginsburg AS, Tinkham L, Riley K, et al.: Antibiotic non-susceptibility among Streptococcus pneumoniae and Haemophilus influenzae isolates identified in African cohorts: a meta-analysis of three decades of published studies. Int. J. Antimicrob. Agents. 2013 Dec; 42(6): 482–491. PubMed Abstract | Publisher Full Text
39. Roca-Oporto C, Cebrero-Cangueiro T, Gil-Marqués ML, et al.: Prevalence and clinical impact of Streptococcus pneumoniae nasopharyngeal carriage in solid organ transplant recipients. BMC Infect. Dis. 2019 Aug 6 [cited 2021 Apr 10]; 19: 697. PubMed Abstract | Publisher Full Text Reference Source
40. Liu S, Dong L, Yang J: Clinical characteristics and antimicrobial resistance of invasive pneumococcal disease in children. Zhonghua Er Ke Za Zhi Chin. J. Pediatr. 2010 Feb; 48(2): 95–99.
41. Franco-Alvarez de Luna F, Causse del Río M, Ibarra González A, et al.: Streptococcus pneumoniae: antibiotic resistance and serotypes in a two-year period. Rev Espanola Quimioter Publicacion of Soc Espanola Quimioter. 2005 Sep; 18(3): 217–221.
42. Capoor MR, Nair D, Aggarwal P, et al.: Rapid diagnosis of community-acquired pneumonia using the BacT/Alert 3D system. Braz. J. Infect. Dis. Off. Publ. Braz. Soc. Infect. Dis. 2006 Oct; 10(5): 352–356. Publisher Full Text
43. Castanheira M, Gales AC, Mendes RE, et al.: Antimicrobial susceptibility of Streptococcus pneumoniae in Latin America: results from five years of the SENTRY Antimicrobial Surveillance Program. Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis. 2004 Jul; 10(7): 645–651. Publisher Full Text
44. Metlay JP, Waterer GW: Treatment of Community-Acquired Pneumonia During the Coronavirus Disease 2019 (COVID-19) Pandemic. Ann. Intern. Med. 2020 Aug 18; 173(4): 304–305. PubMed Abstract | Publisher Full Text
45. Metlay JP, Waterer GW, Long AC, et al.: Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am. J. Respir. Crit. Care Med. 2019 Oct 1; 200(7): e45–e67. PubMed Abstract | Publisher Full Text
46. Shah PM, Stille W: Cefotaxime versus ceftriaxone for the treatment of nosocomial pneumonia results of a multicenter study. Diagn. Microbiol. Infect. Dis. 1995 May; 22(1–2): 171–172. PubMed Abstract | Publisher Full Text
47. Merchant M, Karnad DR, Kanbur AA: Incidence of nosocomial pneumonia in a medical intensive care unit and general medical ward patients in a public hospital in Bombay, India. J. Hosp. Infect. 1998 Jun; 39(2): 143–148. Publisher Full Text
48. Bruch H-P, Kujath P: Study of cefotaxime twice daily for the therapy of postoperative pneumonia. Diagn. Microbiol. Infect. Dis. 1995 May; 22(1–2): 203–207. Publisher Full Text
49. Keller C: Prospective evaluation of twice-daily cefotaxime in the treatment of hospitalized patients with severe infections. Diagn. Microbiol. Infect. Dis. 1995 Jun; 22(1–2): 159–161. Publisher Full Text
50. Garber GE, Auger P, Chan RMT, et al.: A multicenter, open comparative study of parenteral cefotaxime and ceftriaxone in the treatment of nosocomial lower respiratory tract infections. Diagn. Microbiol. Infect. Dis. 1992 Jan; 15(1): 85–88. PubMed Abstract | Publisher Full Text
51. Fernández-Guerrero M, Arnau C, Valdés L, et al.: Nosocomial pneumonia: Comparative multicentre trial between monotherapy with cefotaxime and treatment with antibiotic combinations. Infection. 1991 Jun; 19(S6): S320–S325. PubMed Abstract | Publisher Full Text
52. Díaz A, Torres C, Flores LJ, et al.: Community acquired pneumococcal pneumonia in hospitalized adult patients. Rev. Med. Chil. 2003 May; 131(5): 505–514. PubMed Abstract
53. Maesen FPV, Davies BI, Drenth BMH, et al.: Treatment of acute exacerbations of chronic bronchitis with cefotaxime: a controlled clinical trial. J. Antimicrob. Chemother. 1980 Jan 1; 6(suppl A): 187–192. PubMed Abstract | Publisher Full Text
54. van Zanten ARH , Oudijk M, Nohlmans-Paulssen MKE, et al.: Continuous vs. intermittent cefotaxime administration in patients with chronic obstructive pulmonary disease and respiratory tract infections: pharmacokinetics/pharmacodynamics, bacterial susceptibility and clinical efficacy. Br. J. Clin. Pharmacol. 2007 Jan; 63(1): 100–109. PubMed Abstract | Publisher Full Text
55. Tackett KL, Atkins A: Evidence-Based Acute Bronchitis Therapy. J. Pharm. Pract. 2012 Dec 1; 25(6): 586–590. Publisher Full Text
56. Worrall G: Acute bronchitis. Can. Fam. Physician. 2008 Feb; 54(2): 238–239.
57. Rylski M, Stelmaska-Dworak E, Andrzejewski K: Aerobic and anaerobic bacterial flora as a cause of lower respiratory tract infection. Pneumonol. Alergol. Pol. 1993; 61(3–4): 144–147. PubMed Abstract
58. Konishi K, Takishima T, Honda I, et al.: Clinical evaluation of cefotaxime in internal medicine. Jpn. J. Antibiot. 1983 Jul; 36(7): 1653–1675. PubMed Abstract

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Critical Care Services, CHL Hospital, Indore, Madhya Pradesh, India

Nikhilesh Jain
Roles: Project Administration, Supervision, Validation, Writing – Review & Editing

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No competing interests were disclosed.

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The author(s) declared that no grants were involved in supporting this work.

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Jain N. Cefotaxime: A reappraisal for use in lower respiratory tract infections [version 1; peer review: 1 not approved]. F1000Research 2022, 11:350 (https://doi.org/10.12688/f1000research.74850.1)

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Reviewer Report 13 Jun 2022

Wojciech Feleszko, Medical University of Warsaw, Warsaw, Poland

Not Approved

https://doi.org/10.5256/f1000research.78649.r138030

I started reading Nikhilesh Jain's article with great enthusiasm, which is an extensive discussion of the properties of cefotaxime. It is a complete discussion of this drug's pharmacological, antimicrobial, and clinical properties. The author has included several tables showing, for ... Continue reading

I started reading Nikhilesh Jain's article with great enthusiasm, which is an extensive discussion of the properties of cefotaxime. It is a complete discussion of this drug's pharmacological, antimicrobial, and clinical properties. The author has included several tables showing, for example, the spectrum of antibacterial activity of this antibiotic that we have known for years.

It is an antibiotic known as an effective weapon in lower respiratory tract infections, effective and readily used for years. It has a particularly high therapeutic potential in lower respiratory tract infections, as shown by the author of this paper. However, I cannot help feeling that I am reading a package insert or a chapter in a pharmacology textbook.

Why?

First of all, the scientific article lacks a critical and balanced view of this drug, especially compared to its biggest competitor - ceftriaxone. Both drugs have an identical antimicrobial spectrum, similar indications, and clinical use. So why is one of them used more often? Why would cefotaxime be better? Such comparisons are sorely lacking in this article.

Similarly, I miss figures, for example, illustrating the mechanism of action or the diseases in which it is used. In particular, I also miss such a figure which would compare both drugs.

The article is a good compendium about one well-known drug, but I did not get the impression that there was anything particularly cutting-edge in the research on this drug in the last two to three years.

Perhaps it is worth examining the databases for the last five years to see these new perspectives?
Perhaps it is worth placing more emphasis on the position of this drug in the context of growing antibiotic resistance (e.g., ¹^,², also on cefotaxime³, or show the geographical differences in the use of drugs of this group in different countries and continents ³.

Such an analysis would significantly improve the quality of this paper. However, I do not recommend it for indexing in its current form.

Is the topic of the review discussed comprehensively in the context of the current literature?

No
Are all factual statements correct and adequately supported by citations?

Yes
Is the review written in accessible language?

Yes
Are the conclusions drawn appropriate in the context of the current research literature?

No

References

1. Kiedrowska M, Foryś WJ, Gołębiewska A, Waśko I, et al.: Antimicrobial resistance among Haemophilus influenzae isolates responsible for lower respiratory tract infections in Poland, 2005-2019.Eur J Clin Microbiol Infect Dis. 2022; 41 (6): 961-969 PubMed Abstract | Publisher Full Text
2. Van Besien RF, Hampton N, Micek ST, Kollef MH: Ceftriaxone resistance and adequacy of initial antibiotic therapy in community onset bacterial pneumonia.Medicine (Baltimore). 2022; 101 (20): e29159 PubMed Abstract | Publisher Full Text
3. Varghese R, Basu S, Neeravi A, Pragasam A, et al.: Emergence of Meropenem Resistance Among Cefotaxime Non-susceptible Streptococcus pneumoniae: Evidence and Challenges.Front Microbiol. 2021; 12: 810414 PubMed Abstract | Publisher Full Text

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: pediatric pulmonology, LTRI, immunology, respiratory viruses, bronchiolitis, pneumonia,

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

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Wojciech Feleszko, Medical University of Warsaw, Warsaw, Poland
Kazuhiro Ishikawa, St. Luke's International Hospital, Tokyo, Japan

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Reviewer Report

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04 Aug 2023 | for Version 2

Kazuhiro Ishikawa, St. Luke's International Hospital, Tokyo, Japan

12 Views Cite this report Responses(0)

Not Approved

The study discussed the benefits and drawbacks of using third-generation cephalosporins, specifically ceftriaxone and cefotaxime, in clinical practice. The authors note that ceftriaxone is commonly used due to its ease of use, but there is little information regarding the significant advantages of cefotaxime. They also report on potential side effects associated with ceftriaxone, but the frequency and severity of these side effects are not clearly defined. The authors emphasize that while cefepime is often associated with neurotoxicity, ceftriaxone is not commonly associated with this adverse effect. The study also references the use of third-generation cephalosporins in the treatment of hospital-acquired pneumonia, but notes that the prevalence of ampC-producing bacteria may make these drugs less effective as first-line treatment. The authors provide a table of common causative agents of community-acquired pneumonia, but note that Pseudomonas aeruginosa, which is often associated with cefotaxime use, is not typically the leading cause. Finally, the authors note that ceftriaxone may be used without dose adjustment in patients with renal dysfunction and has good CNS penetration, but do not provide information on these characteristics in relation to cefotaxime. Overall, the study suggests that there may be reporting bias regarding the efficacy of cefotaxime compared to ceftriaxone, and more research is needed to clarify the benefits and drawbacks of these drugs in clinical practice.

Is the topic of the review discussed comprehensively in the context of the current literature?

Partly
Are all factual statements correct and adequately supported by citations?

Partly
Is the review written in accessible language?

Yes
Are the conclusions drawn appropriate in the context of the current research literature?

Partly

References

1. Smith C, Petty B, Hendrix C, Kernan W, et al.: Ceftriaxone Compared with Cefotaxime for Serious Bacterial Infections. Journal of Infectious Diseases. 1989; 160 (3): 442-447 Publisher Full Text
2. Gerstner GJ: Comparison of ceftriaxone (1 x 1 g/day) versus cefotaxime (3 x 1 g/day) for gynecologic and obstetric infections. A randomized clinical trial.Gynecol Obstet Invest. 1990; 29 (4): 273-7 PubMed Abstract | Publisher Full Text

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

infection disease, meta-analysis

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

Respond to this report

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Reviewer Report

45 Views

13 Jun 2022 | for Version 1

Wojciech Feleszko, Medical University of Warsaw, Warsaw, Poland

45 Views Cite this report Responses(0)

Not Approved

I started reading Nikhilesh Jain's article with great enthusiasm, which is an extensive discussion of the properties of cefotaxime. It is a complete discussion of this drug's pharmacological, antimicrobial, and clinical properties. The author has included several tables showing, for example, the spectrum of antibacterial activity of this antibiotic that we have known for years.

It is an antibiotic known as an effective weapon in lower respiratory tract infections, effective and readily used for years. It has a particularly high therapeutic potential in lower respiratory tract infections, as shown by the author of this paper. However, I cannot help feeling that I am reading a package insert or a chapter in a pharmacology textbook.

Why?

First of all, the scientific article lacks a critical and balanced view of this drug, especially compared to its biggest competitor - ceftriaxone. Both drugs have an identical antimicrobial spectrum, similar indications, and clinical use. So why is one of them used more often? Why would cefotaxime be better? Such comparisons are sorely lacking in this article.

Similarly, I miss figures, for example, illustrating the mechanism of action or the diseases in which it is used. In particular, I also miss such a figure which would compare both drugs.

The article is a good compendium about one well-known drug, but I did not get the impression that there was anything particularly cutting-edge in the research on this drug in the last two to three years.

Perhaps it is worth examining the databases for the last five years to see these new perspectives?
Perhaps it is worth placing more emphasis on the position of this drug in the context of growing antibiotic resistance (e.g., ¹^,², also on cefotaxime³, or show the geographical differences in the use of drugs of this group in different countries and continents ³.

Such an analysis would significantly improve the quality of this paper. However, I do not recommend it for indexing in its current form.

Is the topic of the review discussed comprehensively in the context of the current literature?

No
Are all factual statements correct and adequately supported by citations?

Yes
Is the review written in accessible language?

Yes
Are the conclusions drawn appropriate in the context of the current research literature?

No

References

1. Kiedrowska M, Foryś WJ, Gołębiewska A, Waśko I, et al.: Antimicrobial resistance among Haemophilus influenzae isolates responsible for lower respiratory tract infections in Poland, 2005-2019.Eur J Clin Microbiol Infect Dis. 2022; 41 (6): 961-969 PubMed Abstract | Publisher Full Text
2. Van Besien RF, Hampton N, Micek ST, Kollef MH: Ceftriaxone resistance and adequacy of initial antibiotic therapy in community onset bacterial pneumonia.Medicine (Baltimore). 2022; 101 (20): e29159 PubMed Abstract | Publisher Full Text
3. Varghese R, Basu S, Neeravi A, Pragasam A, et al.: Emergence of Meropenem Resistance Among Cefotaxime Non-susceptible Streptococcus pneumoniae: Evidence and Challenges.Front Microbiol. 2021; 12: 810414 PubMed Abstract | Publisher Full Text

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

pediatric pulmonology, LTRI, immunology, respiratory viruses, bronchiolitis, pneumonia,

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

Respond to this report

Responses (0)

[1] 1. Wang M, Zhou Y, Zong Z, et al.: A precision medicine approach to managing 2019 novel coronavirus pneumonia. Precis. Clin. Med. 2020 Mar 25; 3(1): 14–21. PubMed Abstract | Publisher Full Text

[2] 2. Feldman C, Richards G: Appropriate antibiotic management of bacterial lower respiratory tract infections. F1000Research. 2018 Jul 23; 7: 1121. PubMed Abstract | Publisher Full Text

[3] 3. Troeger C, Blacker B, Khalil IA, et al.: Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect. Dis. 2018 Nov 1; 18(11): 1191–1210. PubMed Abstract | Publisher Full Text

[4] 4. Cassir N, Rolain J-M, Brouqui P: A new strategy to fight antimicrobial resistance: the revival of old antibiotics. Front. Microbiol. 2014 [cited 2021 Apr 5]; 5. PubMed Abstract | Publisher Full Text

[5] 5. Dasaraju PV, Liu C: Infections of the Respiratory System. Baron S, editor. Medical Microbiology. 4th ed.Galveston (TX): University of Texas Medical Branch at Galveston; 1996 [cited 2021 Apr 6]. Reference Source

[6] 6. Woodhead M, Blasi F, Ewig S, et al.: Guidelines for the management of adult lower respiratory tract infections - Summary. Clin. Microbiol. Infect. 2011 Nov 1; 17: 1–24. PubMed Abstract | Publisher Full Text

[7] 7. WHO|Pneumonia: the forgotten killer of children: WHO. World Health Organization. [cited 2021 Apr 6]. Reference Source

[8] 8. Pneumonia: [cited 2021 Apr 6]. Reference Source

[9] 9. Mahashur A: Management of lower respiratory tract infection in outpatient settings: Focus on clarithromycin. Lung India Off. Organ Indian Chest Soc. 2018 Apr; 35(2): 143–149. PubMed Abstract | Publisher Full Text

[10] 10. Malosh RE, Martin ET, Ortiz JR, et al.: The risk of lower respiratory tract infection following influenza virus infection: A systematic and narrative review. Vaccine. 2018 Jan 2; 36(1): 141–147. PubMed Abstract | Publisher Full Text

[11] 11. Khan S, Priti S, Ankit S: Bacteria Etiological Agents Causing Lower Respiratory Tract Infections and Their Resistance Patterns. Iran. Biomed. J. 2015 Oct; 19(4): 240–246. PubMed Abstract

[12] 12. Ieven M, Coenen S, Loens K, et al.: Aetiology of lower respiratory tract infection in adults in primary care: a prospective study in 11 European countries. Clin. Microbiol. Infect. 2018 Nov 1; 24(11): 1158–1163. PubMed Abstract | Publisher Full Text

[13] 13. Abdullah FE, Ahuja KR, Kumar H: Prevalence and emerging resistance of Moraxella catarrhalis in lower respiratory tract infections in Karachi. JPMA J. Pak. Med. Assoc. 2013 Nov; 63(11): 1342–1344.

[14] 14. Thiem U, Heppner H-J, Pientka L: Elderly patients with community-acquired pneumonia: optimal treatment strategies. Drugs Aging. 2011 Jul 1; 28(7): 519–537. Publisher Full Text

[15] 15. Forum of International Respiratory Societies, European Respiratory Society: The global impact of respiratory disease.2017.

[16] 16. Indian Pediatrics - Editorial: [cited 2021 Apr 6]. Reference Source

[17] 17. Zampieri FG, Póvoa P, Salluh JI, et al.: Lower Respiratory Tract Infection and Short-Term Outcome in Patients With Acute Respiratory Distress Syndrome. J. Intensive Care Med. 2018 Apr 26; 35(6): 588–594. Publisher Full Text

[18] 18. Klein NC, Cunha BA: The selection and use of cephalosporins: a review. Adv. Ther. 1995 Apr; 12(2): 83–101.

[19] 19. Arumugham VB, Cascella M: Third Generation Cephalosporins. StatPearls. Treasure Island (FL): StatPearls Publishing; 2021 [cited 2021 Apr 1]. Reference Source

[20] 20. El-Shaboury SR, Saleh GA, Mohamed FA, et al.: Analysis of cephalosporin antibiotics. J. Pharm. Biomed. Anal. 2007 Sep 21; 45(1): 1–19. Publisher Full Text

[21] 21. Classification of Cephalosporin Antibiotics. MediMoon. 2013 [cited 2021 Apr 5]. Reference Source

[22] 22. Dudley MN, Barriere SL: Cefotaxime: microbiology, pharmacology, and clinical use. Clin. Pharm. 1982 Apr; 1(2): 114–124. PubMed Abstract

[23] 23. Plosker GL, Foster RH, Benfield P: Cefotaxime. A pharmacoeconomic review of its use in the treatment of infections. PharmacoEconomics. 1998 Jan; 13(1 Pt 1): 91–106. Publisher Full Text

[24] 24. Cefotaxime (Cefotaxime for Injection): Uses, Dosage, Side Effects, Interactions, Warning: RxList. [cited 2021 Apr 4]. Reference Source

[25] 25. Padda IS, Nagalli S: Cefotaxime. StatPearls. Treasure Island (FL): StatPearls Publishing; 2021 [cited 2021 Apr 3]. Reference Source

[26] 26. Coombes JD: Metabolism of cefotaxime in animals and humans. Rev. Infect. Dis. 1982 Oct; 4 Suppl: S325–S332. PubMed Abstract | Publisher Full Text

[27] 27. Chin NX, Neu HC: Cefotaxime and desacetylcefotaxime: an example of advantageous antimicrobial metabolism. Diagn. Microbiol. Infect. Dis. 1984 Jun; 2(3 Suppl): 21S–31S. PubMed Abstract

[28] 28. Antibacterial Activity of Desacetylcefotaxime alone and in combination with Cefotaxime by Harold C. Neu Reviews of Infectious diseases. September-October 1982; 4(Supplement _2): S374–S378. Publisher Full Text

[29] 29. Castle SS: Cefotaxime. Enna SJ, Bylund DB, editors. xPharm: The Comprehensive Pharmacology Reference. New York: Elsevier; 2007 [cited 2021 Apr 11]; p. 1–4. Reference Source

[30] 30. Carmine AA, Brogden RN, Heel RC, et al.: Cefotaxime. A review of its antibacterial activity, pharmacological properties and therapeutic use. Drugs. 1983 Mar; 25(3): 223–289. PubMed Abstract | Publisher Full Text

[31] 31. Wittmann DH, Jones RN, Malledant J, et al.: Cefotaxime in the treatment of prophylaxis of surgical infections. J. Chemother. Florence Italy. 1997 May; 9 Suppl 2: 19–33.

[32] 32. Pneumoni, samfunnservervet: Helsedirektoratet.[cited 2021 Apr 8]. Reference Source

[33] 33. Høgli JU, Garcia BH, Svendsen K, et al.: Empirical prescribing of penicillin G/V reduces risk of readmission of hospitalized patients with community-acquired pneumonia in Norway: a retrospective observational study. BMC Pulm. Med. 2020 Jun 15 [cited 2021 Apr 8]; 20: 169. PubMed Abstract | Publisher Full Text Reference Source

[34] 34. Blanco-Iglesias E, Oñoro G, Almodovar-Martín JL, et al.: Retrospective Study in Children With Necrotizing Pneumonia: Nine Years of Intensive Care Experience. Pediatr. Infect. Dis. J. 2020 Jul; 39(7): 571–575. Publisher Full Text

[35] 35. Antibiotic Resistance Profiles of Haemophilus influenzae Isolates from Children in 2016: A Multicenter Study in China - PubMed.[cited 2021 Apr 10]. Reference Source

[36] 36. Lu Y-Y, Luo R, Fu Z: Pathogen distribution and bacterial resistance in children with severe community-acquired pneumonia. Zhongguo Dang Dai Er Ke Za Zhi Chin J Contemp Pediatr. 2017 Sep; 19(9): 983–988.

[37] 37. Hoa NQ, Trung NV, Larsson M, et al.: Decreased Streptococcus pneumoniae susceptibility to oral antibiotics among children in rural Vietnam: a community study. BMC Infect. Dis. 2010 Mar 31; 10: 85. PubMed Abstract | Publisher Full Text

[38] 38. Ginsburg AS, Tinkham L, Riley K, et al.: Antibiotic non-susceptibility among Streptococcus pneumoniae and Haemophilus influenzae isolates identified in African cohorts: a meta-analysis of three decades of published studies. Int. J. Antimicrob. Agents. 2013 Dec; 42(6): 482–491. PubMed Abstract | Publisher Full Text

[39] 39. Roca-Oporto C, Cebrero-Cangueiro T, Gil-Marqués ML, et al.: Prevalence and clinical impact of Streptococcus pneumoniae nasopharyngeal carriage in solid organ transplant recipients. BMC Infect. Dis. 2019 Aug 6 [cited 2021 Apr 10]; 19: 697. PubMed Abstract | Publisher Full Text Reference Source

[40] 40. Liu S, Dong L, Yang J: Clinical characteristics and antimicrobial resistance of invasive pneumococcal disease in children. Zhonghua Er Ke Za Zhi Chin. J. Pediatr. 2010 Feb; 48(2): 95–99.

[41] 41. Franco-Alvarez de Luna F, Causse del Río M, Ibarra González A, et al.: Streptococcus pneumoniae: antibiotic resistance and serotypes in a two-year period. Rev Espanola Quimioter Publicacion of Soc Espanola Quimioter. 2005 Sep; 18(3): 217–221.

[42] 42. Capoor MR, Nair D, Aggarwal P, et al.: Rapid diagnosis of community-acquired pneumonia using the BacT/Alert 3D system. Braz. J. Infect. Dis. Off. Publ. Braz. Soc. Infect. Dis. 2006 Oct; 10(5): 352–356. Publisher Full Text

[43] 43. Castanheira M, Gales AC, Mendes RE, et al.: Antimicrobial susceptibility of Streptococcus pneumoniae in Latin America: results from five years of the SENTRY Antimicrobial Surveillance Program. Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis. 2004 Jul; 10(7): 645–651. Publisher Full Text

[44] 44. Metlay JP, Waterer GW: Treatment of Community-Acquired Pneumonia During the Coronavirus Disease 2019 (COVID-19) Pandemic. Ann. Intern. Med. 2020 Aug 18; 173(4): 304–305. PubMed Abstract | Publisher Full Text

[45] 45. Metlay JP, Waterer GW, Long AC, et al.: Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am. J. Respir. Crit. Care Med. 2019 Oct 1; 200(7): e45–e67. PubMed Abstract | Publisher Full Text

[46] 46. Shah PM, Stille W: Cefotaxime versus ceftriaxone for the treatment of nosocomial pneumonia results of a multicenter study. Diagn. Microbiol. Infect. Dis. 1995 May; 22(1–2): 171–172. PubMed Abstract | Publisher Full Text

[47] 47. Merchant M, Karnad DR, Kanbur AA: Incidence of nosocomial pneumonia in a medical intensive care unit and general medical ward patients in a public hospital in Bombay, India. J. Hosp. Infect. 1998 Jun; 39(2): 143–148. Publisher Full Text

[48] 48. Bruch H-P, Kujath P: Study of cefotaxime twice daily for the therapy of postoperative pneumonia. Diagn. Microbiol. Infect. Dis. 1995 May; 22(1–2): 203–207. Publisher Full Text

[49] 49. Keller C: Prospective evaluation of twice-daily cefotaxime in the treatment of hospitalized patients with severe infections. Diagn. Microbiol. Infect. Dis. 1995 Jun; 22(1–2): 159–161. Publisher Full Text

[50] 50. Garber GE, Auger P, Chan RMT, et al.: A multicenter, open comparative study of parenteral cefotaxime and ceftriaxone in the treatment of nosocomial lower respiratory tract infections. Diagn. Microbiol. Infect. Dis. 1992 Jan; 15(1): 85–88. PubMed Abstract | Publisher Full Text

[51] 51. Fernández-Guerrero M, Arnau C, Valdés L, et al.: Nosocomial pneumonia: Comparative multicentre trial between monotherapy with cefotaxime and treatment with antibiotic combinations. Infection. 1991 Jun; 19(S6): S320–S325. PubMed Abstract | Publisher Full Text

[52] 52. Díaz A, Torres C, Flores LJ, et al.: Community acquired pneumococcal pneumonia in hospitalized adult patients. Rev. Med. Chil. 2003 May; 131(5): 505–514. PubMed Abstract

[53] 53. Maesen FPV, Davies BI, Drenth BMH, et al.: Treatment of acute exacerbations of chronic bronchitis with cefotaxime: a controlled clinical trial. J. Antimicrob. Chemother. 1980 Jan 1; 6(suppl A): 187–192. PubMed Abstract | Publisher Full Text

[54] 54. van Zanten ARH , Oudijk M, Nohlmans-Paulssen MKE, et al.: Continuous vs. intermittent cefotaxime administration in patients with chronic obstructive pulmonary disease and respiratory tract infections: pharmacokinetics/pharmacodynamics, bacterial susceptibility and clinical efficacy. Br. J. Clin. Pharmacol. 2007 Jan; 63(1): 100–109. PubMed Abstract | Publisher Full Text

[55] 55. Tackett KL, Atkins A: Evidence-Based Acute Bronchitis Therapy. J. Pharm. Pract. 2012 Dec 1; 25(6): 586–590. Publisher Full Text

[56] 56. Worrall G: Acute bronchitis. Can. Fam. Physician. 2008 Feb; 54(2): 238–239.

[57] 57. Rylski M, Stelmaska-Dworak E, Andrzejewski K: Aerobic and anaerobic bacterial flora as a cause of lower respiratory tract infection. Pneumonol. Alergol. Pol. 1993; 61(3–4): 144–147. PubMed Abstract

[58] 58. Konishi K, Takishima T, Honda I, et al.: Clinical evaluation of cefotaxime in internal medicine. Jpn. J. Antibiot. 1983 Jul; 36(7): 1653–1675. PubMed Abstract

­­­­­Cefotaxime: A reappraisal for use in lower respiratory tract infections

Abstract

Keywords

Introduction

LRTI

Table 1. Common terms related to LRTI.

Disease burden in various age groups

Microbial spectrum

Table 2. Lower respiratory tract infectioms: common causative microorganisms.

Risk factors for LRTI

Cefotaxime: molecular profile

Table 3. Classification of Cephalosporins.21

Molecular structure

Intrinsic activity and spectrum of action

Table 4. Organisms sensitive to cefotaxime.25

Clinical pharmacology

Administration and dose

Table 5. General dosing guidelines for cefotaxime.24

Key advantages

Cefotaxime: clinical evidence in LRTI

Community acquired pneumonia (CAP)

CAP during Coronavirus Disease 2019 (COVID-19) pandemic

Nosocomial or hospital-acquired pneumonia

Acute exacerbations of chronic bronchitis (AECB)

Acute bronchitis

Conclusions

Data availability

References

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Cefotaxime: A reappraisal for use in lower respiratory tract infections

Table 3. Classification of Cephalosporins.²¹

Table 4. Organisms sensitive to cefotaxime.²⁵

Table 5. General dosing guidelines for cefotaxime.²⁴